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About the NATPARA
Recall

What You Need to Know

After discussions with the FDA, Takeda issued a US recall on September 5, 2019, for all doses of NATPARA® (parathyroid hormone) for Injection (25 mcg, 50 mcg, 75 mcg, and 100 mcg).

NATPARA is a parathyroid hormone currently approved in the US as the only adjunctive treatment for adult patients with chronic hypoparathyroidism who cannot be adequately controlled with standard therapy alone (calcium and vitamin D).

With patient safety as the company’s main priority, Takeda is communicating directly with US healthcare professionals as well as with patients and specialty pharmacies. Discontinuing NATPARA abruptly can cause a decrease in blood calcium levels (severe hypocalcemia) which can result in serious health consequences. It is critically important that patients contact their prescribing healthcare provider to discuss their individual treatment plan and ensure close supervision, including frequent monitoring of blood calcium levels and close titration of active vitamin D and calcium supplements upon stopping NATPARA to avoid low blood calcium (hypocalcemia).

All of us at Takeda understand the impact that this recall has on patients, and we are continuing to work closely with the FDA until we are able to resolve the issue. Takeda values the US FDA’s collaboration and feedback as we work together to resupply NATPARA to patients who need it.

If you have questions or concerns about this recall, browse the information on this page.

Questions?

Physicians with a medical question should contact
MedInfoUS@takeda.com

If your question is not medical-related, please email
NatparaNonMedical@takeda.com

Listen: Community Call

Takeda hosted a call on April 12, 2022, to update the hypoparathyroidism patient community on the latest details supporting the NATPARA recall. Listen to the complete recording, or read the full transcript, below.

This is an audio recording of a call intended to update the hypopara patient community regarding the ongoing NATPARA recall.

NATPARA is a prescription parathyroid hormone used with calcium and vitamin D to control low blood calcium (hypocalcemia) in people with low parathyroid hormone blood levels (hypoparathyroidism). It is only for people who do not respond well to treatment with calcium and active forms of vitamin D alone, because it may increase the possible risk of bone cancer (osteosarcoma). NATPARA was not studied in people with hypoparathyroidism caused by calcium-sensing receptor mutations. It was not studied in people who get sudden hypoparathyroidism after surgery. It is not known if NATPARA is safe and effective for children 18 years of age and younger. NATPARA should not be used in children and young adults whose bones are still growing.

During animal drug testing, NATPARA caused some rats to develop a bone cancer called osteosarcoma. It is not known if people who take NATPARA will have a higher chance of getting osteosarcoma. Tell your doctor right away if you have pain in any areas of your body that does not go away, or any new or unusual lumps or swelling under your skin that is tender to touch.

Please listen to this audio in full for additional Important Safety Information about NATPARA. Please also see the Prescribing Information, Medication Guide, and Instructions for Use available on NATPARA.com.

Cheryl Schwartz:

Good evening and thank you all for taking the time to join this evening. My name is Cheryl Schwartz and I lead Takeda’s U.S. Rare Disease Business Unit. And I’m joined tonight by Tom Koutsavlis who is our U.S. head of medical affairs and our chief medical officer, and in just a few moments we'll be joined for a Q and A session, also by Tony Frangie, who leads our U.S. Endocrinology and Lysosomal Storage Disorders Franchise. So, we wanted to set up this call to provide some additional context around our lead March communication and inform the community that we have received a Complete Response Letter from the FDA. As part of that communication, we also shared very difficult news that Natpara’s commercial return to the U.S. market is indefinitely delayed. I want to sincerely thank our advocacy partners. From them we have received questions from the hypopara community and we're going to try our best to answer as many of those as we can tonight.

But first I want to give you a little bit of background from myself and from Tom about the situation for those of you who are, who haven't been as up to speed on what's been happening. So, I’m going to start with the Complete Response Letter. So, on March 22nd we announced that the FDA issued a Complete Response Letter, sometimes we also call this CRL, in response to our Prior Approval Supplements that we submitted in August of 2021 and that Prior Approval Supplement (or PAS, as we sometimes call it), as well, was to address the potential for the rubber particulate formation, which was the issue that led to the original U.S. Natpara recall back in September 2019. So, the CRL that we got back indicated that the FDA had completed its review of the Natpara Prior Approval Supplement and have determined that it cannot be approved in its present form. So, before we talk more about the CRL and next steps, I just want to take a moment, first and foremost, to reinforce that we remain committed to providing patients who are enrolled in the Natpara Special Use Program with continued access to therapy free of charge, in accordance with the regulatory oversight and under the discretion of the FDA. And we're going to talk more about the Special Use Program because I know that there might be some additional questions about that as well; we'll come back to that in a little bit, but I wanted to just take a moment to reinforce that that’s an incredibly important point for people who are depending on that program. So, what happens next in terms of the CRL? So, when a manufacturer receives a Complete Response Letter from the U.S. FDA, the manufacturer has one year to evaluate next steps.

Review timelines are determined by FDA and at the time of submission, so we are in the middle of this process now, but all of these different variables about the uncertainty of the timeline are really part of the reason that we made a very difficult decision to communicate this idea of an indefinite delay to the U.S. market. But there's also another equally important piece of the puzzle here that's also contributing to Natpara’s delay in the U.S. and that's something that we've talked about in the past, which is the protein—particle related supply issues. So, that issue, as you, as we've talked about in the past, is separate from the rubber particulate issue and to address this in more detail I’m going to hand it over to Tom, who's going to talk specifically about the protein—particle related supply issues and how they fit into the bigger picture.

Tom Koutsavlis:

Thanks Cheryl. I am happy to jump in and share some of that thinking as well, and a big thank you to all of you for joining us this evening, very much appreciate your connecting on the call. So as Cheryl was just explaining the PAS approval was the required step to address the issue of the rubber particle formation and that's what led to the original U.S. recall. However, we also still continue to experience supply challenges that surround the protein particle formation and we've described that, I think, to you over the last year and a half, and that is unrelated to the initial recall, so it's important to keep that in mind, that's a second issue. And as we mentioned before, over the last 18 months we've had a higher percentage of our product batches that are not meeting the visual inspection requirements. Specifically, because they have the presence of those protein particles, and obviously they've contributed to intermittent supply interruption. So that's been a significant challenge and, for example, as some of you know we're currently in a shortage of our hundred microgram dose in the Special Use Program, which has required physicians to provide alternative prescriptions or alternate dosing regimens and now unfortunately we're also anticipating that the Natpar product in Europe, known as Natpar as opposed to Natpara, will also unfortunately experience a stock- out of that hundred microgram dose sometime in late June or early July of this year. And I know that our team in Europe now is also in the process of reaching out to all of the healthcare providers and patients with the information to be able to appropriately take next steps. So that's still that challenge on the protein particle side that I think is important for everyone to understand and that's created a lot of our supply questions and challenges that we faced. So over the past year we've done rigorous testing to understand why there are an increasing number of batches that have not met that visual inspection and why that's happening at a higher rate than we had before, and also why some of these failures appear to be impacting more the higher concentrations, the 100 microgram dose, for example, at higher rates than the other doses. So obviously supply continuity for SUP patients is our priority, so we're continuing to work very diligently to address the issues themselves on those protein particles with obviously the goal of trying to prevent any further supply interruptions. Now, as we all know, due to the serious risks of abrupt discontinuation of Natpara, we've always said that addressing these separate supply challenges in a way that enables us to provide that long-term, reliable, and consistently available products supply to you would be critical in bringing back Natpara to the Community, to that broader U.S. hypoparathyroid community. So, it's important also to note that any product that we release, all product that we release continues to meet all of the Takeda quality standards and the safety of Natpara has not changed. If it does not meet those quality standards. For example, if we have any particle concerns in terms of protein particle then that product does not go out the door and, hence, obviously the supply challenge that we're in now. So, this brings us back to Cheryl's initial comment and initial discussion around that indefinite delay. Throughout the last two and a half years, the last thing we wanted to do is provide any false hope or raise the wrong promise to the Community that we wouldn't be able to keep in terms of product being available to you and we know how painful these ongoing timing delays have been for those of you who have not had access to Natpara since obviously before the recall. And at this point it's difficult, it doesn't make sense, to try and predict how long it's going to take to address the FDA’s feedback on rubber particulate questions and initial PAS that Cheryl mentioned, and also fix the ongoing protein particles supply questions that we have. So, because of all of these variables that are very complex, and obviously not just a single item but several items, we've made the decision to note that the U.S. market return is indefinite. And that's really to make certain to give you as best an understanding of what we know today and where we're at so that is, that is why we went ahead and communicated that. So, I’ll turn over to Tony because I know many of you have sent in questions over the past few weeks and Tony if you don't mind perhaps walking us through some of those questions and we can help address some of what has come in.

Tony Frangie:

Thanks, Tom. Can you guys hear me, okay?

Tom Koutsavlis:

We do hear you well.

Tony Frangie:

Great. So, you know, thanks you guys for briefing us through and walking us through the situation and thanks everybody that's online right now that submitted questions either directly to us—or I know, Tom you've received some directly yourself—but also thanks to our patient associations and their leadership for also providing some of those questions to us, on behalf of Community members. One of the largest areas that I saw in terms of the incoming questions were related to the Complete Response Letter or the CRL that Cheryl referenced. For example, one question asked was, did the FDA flat out say no, in response to our submission? Maybe Tom if you don't mind, walk us through that.

Tom Koutsavlis:

Yeah, happy to jump in, and I know you're hearing the details of what is a CRL for the first time, and thank you also Cheryl for sharing with the team what Complete Response Letters mean. So, the details of regulatory interactions including CRL (Complete Response Letters) are confidential and typically not made public, so that's the general process of CRLs as we work through the FDA process, but what I can tell you is that, no, that the FDA has not rejected our submission. What we've submitted and our approach has been that prior approval supplement that the PAS that we described. The FDA responded with a Complete Response Letter that included many questions and now our next step is really to look through those questions, evaluate them, and determine as Cheryl mentioned what is that next step in terms of addressing them, so that's really the next step in the process.

Tony Frangie:

Thanks, Tom. So, another question had to do with that interaction with the Agency, but specifically the question that we received was, did Takeda do something to anger the agency, did we do something to make the FDA mad, and did this factor into the response. Cheryl, I know you're familiar with some of the discussions.

Cheryl Schwartz:

Yes, thanks, Tony. I mean we've certainly had lots of conversations and I can say that I feel very confident saying that we have established a relationship with the FDA you know, over the last couple of years that's included, you know, a very open dialogue and very responsive feedback from them. You know this, that there's multiple areas that we're communicating with the FDA, you know, multiple fronts, so we've been in close coordination with them on the Special Use Program, where the FDA has continued to be very responsive to us and our efforts to continue to provide Natpara, you know, to those who are enrolled in the SUP and helping us to think through some of these, you know, these protein particle issues that Tom has talked about to make sure that any product that patients are taking in the SUP program is safe and effective. The FDA also provided, I think you know, very thoughtful and constructive feedback to the Prior Approval Supplements, you know we're still kind of absorbing a lot of information and preparing for, you know, for additional dialogue and now is the time that we need to take to really figure out the next steps. You know, and as Tom mentioned, there are a lot of variables there that have to be considered, which is why it's really difficult to pin it down in terms of what this means in terms of timeline. But you know it has been a very productive collaborative relationship with FDA and I will say, you know, I don't think there's any sense that they don't appreciate, you know, what the patient community is going through—and they do, which is why they've been so supportive of the SUP Program.

Tony Frangie:

Thank you for that. I think, speaking of those next steps, another related question, does the recent rejection mean that the device problems haven’t been resolved at all, or is Takeda somewhat closer to having a solution? Maybe Tom, this is a more technical one, maybe you can help.

Tom Koutsavlis:

Absolutely, thank you, certainly thank you all for the questions. I think it's an important one, so I, as you know, as we previously described, our team has been conducting a significant amount of testing before landing on an approach, reaching that approach that involve changing two components of the device, and this was to address them and show other particle issues, so we put them in a new rubber septum and a new needle with a goal obviously of addressing those rubber particles that caused the initial recall and that Prior Approval Supplement with that new septum and needle was submitted in August of 2021, that included all of those changes. Now we were obviously, while we were optimistic and having that potential solution, we also knew that the outcome was far from certain. It's obviously difficult to know for certain which direction we're going to take on the conversation with the FDA so the FDA now has responded to that PAS that Prior Approval Supplement with questions that we still need to evaluate and really understand that next step, so, while we're still disappointed that the submission itself was not approved, it wouldn't be accurate to say that we haven't made a lot of progress along the way, a lot of testing and a lot of understanding, a lot of working on the new supplement needle, so there's definitely been progress that's been made in the staff progress that we would build.

Tony Frangie:

Well, in terms of the progress, I think the filing and the response, um, Cheryl, the other question we've gotten is something you've made reference to a couple of times tonight already and that's what do we mean when we say that Natpara is quote indefinitely delayed?

Cheryl Schwartz:

Yeah, I think you know, this is something that we struggle with as well, right, we always want to give answers, and we want to be as transparent as we can and get you know people as much information, I think that the indefinitely largely comes from the fact that we just don't know yet what we're dealing with. I think when we say we're indefinitely delayed we're saying that, you know, assessing the feedback that we got from the FDA and evaluating our path forward is going to take some time and then even once we determine what the next potential steps are, it still might be difficult to make timeline predictions. So, because we can't really speculate on how the FDA is going to respond to any new approach that we bring forward, any new resubmission, timing of that could be variable, the data requests needs. It's very similar to the things that we've talked about in the past, but I think at this point, you know, there are just continue to be multiple various variables at play so you know, while we digest the FDA’s feedback and while we figure out next steps it's just difficult to make a timeline prediction and so that's why I think we use the terminology that we did. Um, you know Tony I know you're also really close to this you've worked on this every single day, is there anything else that I missed or that you think you should add here?

Tony Frangie:

No, I mean just my experience so far talking from a number of clinicians and physicians that are that are working in the community and also talking to community members themselves directly. I think, Tom, you said this really well earlier, the last thing that we wanted to do as an organization was to give some kind of false expectation of timing or that wouldn't enable folks to make the appropriate care plans they need to do on an ongoing basis, anyway, so I mean that's part of the reason that we made that difficult decision, I think, to communicate in this way, at this time. You know I guess given that folks are looking for, you know, alternatives, or anything they can do to be as creative as possible, we have, I have received this question from physicians as well as from members of the Community. And maybe Tom this one, I can direct your way. So, the question was since the Natpara pen submission was not approved, is there any way to get the medication approved to be prescribed in something else, like a vial, and then have each dose drawn up with like an insulin syringe or for some alternative method?

Tom Koutsavlis:

I appreciate that question, Tony. I received a question from many of you in the community and very much appreciate you asking. I think now as you've seen over the past several years as we've been working with the regulatory agencies in our own internal processing system to get across some of the hurdles that we need to solve. There are many regulatory steps required to modify a drug delivery device and/or a product that are quite complex, and I think we had spoken about this a little bit before in a previous phone call, in terms of all those regulatory hurdles that we have to go through so unfortunately, just using a new device or a syringe, for that matter, with the existing Natpara product, it's not an approved way to market the medication, so it would require if we went through to go and look at potentially that route, obviously, there would be a lot of testing and analysis and data that we need to generate and it would require that similar regulatory process that would take probably several months to years to generate that data and then file, of course, for regulatory review and continue down that path. So, unfortunately, it's not just a simple as turn of the switch to be able to do that, from that regulatory approach to it would, in essence, be putting a new product through that process or in the space of new device or combination, and so, unfortunately, that regulatory, those regulatory steps cannot be bypassed. That’s still important to go through obviously for safety reasons, and so that unfortunately is not an option.

Tony Frangie:

Excellent, and I think in lieu of having that commercial option available, we did receive this question directly, as well as all of these really, so when Takeda says the company intends to continue the Special Use Program until commercial product is available, does that mean any commercial product or Natpara specifically? And I’ll give a, for example, you know, is the SUP, or the Special Use Program going to be stopped if a different brand of hyperparathyroidism medication is commercially released? Tom, you've really worked hard on the SUP program, maybe you can take this one.

Tom Koutsavlis:

Yeah, happy to take it. It’s a needed question I’ve received as well, Tony, I think, several of us have over the last little while. So, while it's our intent to continue to provide patients who are enrolled in the Natpara SUP program with continued access to therapy free of charge until Natpara is commercially available in the U.S. it's important to remember that the SUP program itself is actually subject to regulatory oversight, so the program was put in place with the discretion of the FDA. Obviously, they’re closely involved with helping us with the program so that it would be available and established to those patients that were at highest risk. If you remember when the product program was first put in place, it was always intended for that extreme risk of life-threatening complications, as a result of the Natpara discontinuation that we went through when the commercial product was no longer available when we went to recall. If Natpara does become commercially available again in the U.S., then obviously that SUP program would change because the program itself is now obviously very specific in this circumstance, when we were in a recall situation and it's important to keep in mind that commercializing Natpara now is not only dependent on addressing this CRL but obviously dealing with the supply challenges as we mentioned from the protein particle piece because it's very critical for us to make sure that, should we come back with product on commercial product on the market, that we have a supply that you would all need to make certain that there are no disruptions going forward. Tony, I think the question itself if the question means perhaps any other commercial product [Tony Frangie: It does], so important now just to keep in mind that there are no other commercial products currently available today and it's obviously hard to speculate if there was a product available, where it may be and what it may or may not do throughout its own development cycle. And it's important for us as a company, of course, not to comment on other pipeline and other commercial products that are not in our portfolio, because those are the ones, we can comment on directly but other company products we wouldn't really be able to.

Tony Frangie:

Well, thanks, Tom, and thanks, Cheryl. Those were the biggest, most common questions that we received and again thank you everyone for submitting them and I’m sure you know, we’ll be getting more questions as time goes on, as we have throughout this process, but thank you, guys, so much. Cheryl, we can turn to you.

Cheryl Schwartz:

Hey thanks, Tony. So, thanks, Tony, thanks, Tom, and thank you all again for those of you who joined tonight's call live or for those who were not able to join live, we will be recording this so people can access it and replay it. And also, a big thanks to everyone who submitted questions. You know, there was a lot of consistency in the questions, so these are definitely the ones that we knew we had to address. You know, just as a reminder to everyone on the call, you know if you have any additional questions or concerns about your own treatment plan, please, I want to encourage you to contact your healthcare professional and have those discussions as well. And also, as Tom mentioned, for those of you are receiving Natpara through the Special Use Program, Takeda’s OnePath support managers will continue to work with you as they have, over the last several years, to ensure that you have access to your prescribed Natpara treatment. So please keep an eye out for communications coming through that channel as well. And, of course, as always, the Hypoparathyroidism Association and also the HypoPara Support and Advocacy Group continue to offer the community at large, you know, education, information, support, advocacy, you know, and we also want to extend a huge thank you to them for continuing to partner with us in this really challenging situation and helping to connect us within the broader community. So, I know this is a lot of information to absorb, as always, it gets very technical very, very quickly. You know as much as we want to be transparent, there are obviously elements that would get even more technical and difficult to explain so thank you for bearing with us as we've gone through some of these details. I did want to close the session by saying, you know, just once again that obviously this latest news was not the update that any of us wanted to deliver. You know this was very challenging news, you know, for all of us, and I know I said this in the past that, you know, often corporate communications can come across as you know, incredibly impersonal despite the very best of intentions. You know, but at the same time, you know it's our job and we're committed to trying to keep the community updated as quickly and transparently as we can. So, you know, if it doesn't come across, you know, in always in the perfect way and I hope that at least some of these calls help to answer your questions and your concerns and, of course, you know your healthcare provider can also help to support you in that way as well. And I also wanted to say that, you know, although you've now seen me and Tom and now Tony a couple of times on these calls, you know what you don't see is actually this huge team of people behind the scenes who are working on this program, and every aspect of this program on the SUP, the patient support managers, from a manufacturing and supply point of view, from a technical point and development point of view, the device team, our quality team, our regulatory teams, so there's a giant group of people that are working um working on Natpara and, you know, also many of those people have really direct personal experiences with rare disease. This is what draws a lot of us to this area is because of our personal connections. So, you know many of us do really understand the impact that news like this has on patients and on their families and we don't want you to think in any way that we underestimate that. So, on behalf of this team here tonight, but also that larger team, I just want to, you know, reiterate that we’re so disappointed that we could not provide better news to you, but we hope that you know that we do remain committed to the SUP and to the community and will continue to keep you updated, you know, as more information becomes available. So, with that I’ll just say again, thank you so much for joining us for your questions and your continued transparency with us and thank you and good night.

Thank you for listening to the recording of this call.  Please stay on to hear Important Safety Information about NATPARA.

Important Safety Information

What is the most important information I should know about NATPARA?

Warning: Possible bone cancer (osteosarcoma).

  • During animal drug testing, NATPARA caused some rats to develop a bone cancer called osteosarcoma. It is not known if people who take NATPARA will have a higher chance of getting osteosarcoma. Tell your doctor right away if you have pain in any areas of your body that does not go away, or any new or unusual lumps or swelling under your skin that is tender to touch.
  • NATPARA is only available through the NATPARA Risk Evaluation and Mitigation Strategy (REMS) Program. The purpose of the NATPARA REMS program is to inform patients about the potential risk of osteosarcoma associated with the use of NATPARA. For more information about this REMS program, call 1-855-NATPARA (628-7272) or go to www.NATPARAREMS.com.

NATPARA may cause other serious side effects, including:

High blood calcium (hypercalcemia)

  • NATPARA can cause some people to have a higher blood calcium level than normal.
    • Your doctor should check your blood calcium before you start and during your treatment with NATPARA.
    • Tell your doctor if you have nausea, vomiting, constipation, low energy, or muscle weakness. These may be signs that you have too much calcium in your blood.

Low blood calcium (hypocalcemia)

  • People who stop using or miss a dose of NATPARA may have an increased risk of severe low blood calcium levels.
  • Tell your doctor if you have tingling of your lips, tongue, fingers and feet, twitching of face muscles, cramping of feet and hands, seizures, depression, or have problems thinking or remembering.

Tell your doctor right away if you have any of these signs and symptoms of high or low blood calcium levels.

Who should not use NATPARA?

Do not use NATPARA if you are allergic to parathyroid hormone or any of the ingredients in NATPARA.

What should I tell my healthcare provider before using NATPARA?

Before you start using NATPARA, tell your doctor about all of your medical conditions. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of NATPARA?

NATPARA may cause serious side effects like allergic (hypersensitivity) reaction, including anaphylaxis. Tell your healthcare provider or get emergency medical help right away if you have any of the following symptoms of an allergic reaction:

  • swelling of your face, lips, mouth, or tongue
  • breathing problems
  • fainting, dizziness, feeling lightheaded (low blood pressure)
  • fast heartbeat
  • itching
  • rash
  • hives

The most common side effects of NATPARA include: tingling, tickling, or burning feeling of the skin, low or high blood calcium, headache, nausea, reduced sense of touch or sensation, diarrhea, vomiting, pain in joints, too much calcium in urine, and pain in limbs.

These are not all the possible side effects of NATPARA. For more information, talk with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see Prescribing Information, Medication Guide, and Instructions for Use available on NATPARA.COM.

Thank you!

Takeda hosted a call on April 26, 2021, to update the hypoparathyroidism patient community on the NATPARA recall. Listen to the complete recording, or read the full transcript, below.

This is an audio recording of a call intended to update the hypopara patient community regarding the ongoing NATPARA recall.

NATPARA is a prescription parathyroid hormone used with calcium and vitamin D to control low blood calcium (hypocalcemia) in people with low parathyroid hormone blood levels (hypoparathyroidism). It is only for people who do not respond well to treatment with calcium and active forms of vitamin D alone, because it may increase the possible risk of bone cancer (osteosarcoma). NATPARA was not studied in people with hypoparathyroidism caused by calcium-sensing receptor mutations. It was not studied in people who get sudden hypoparathyroidism after surgery. It is not known if NATPARA is safe and effective for children 18 years of age and younger. NATPARA should not be used in children and young adults whose bones are still growing.

During animal drug testing, NATPARA caused some rats to develop a bone cancer called osteosarcoma. It is not known if people who take NATPARA will have a higher chance of getting osteosarcoma. Tell your doctor right away if you have pain in any areas of your body that does not go away, or any new or unusual lumps or swelling under your skin that is tender to touch.

Please listen to this audio in full for additional Important Safety Information about NATPARA. Please also see the Prescribing Information, Medication Guide, and Instructions for Use available on NATPARA.com.

Operator:

My name is Matthew and I will be your event specialist today. At this time, I would like to welcome everyone to today's web conference. All lines have been placed on mute to prevent any background noise. Please note that today's web conference is being recorded.

Today's presenters will appear on webcam on your screen. You can change the layout of your screen at any time in WebEx. Locate the layout option and select great or stage view on the top right side of your screen to toggle between views as needed.

It is now my pleasure to turn today's program over to your moderator Cheryl Schwartz, Head of the Takeda U.S. Rare Disease Business Unit. Cheryl, the floor is yours.

Cheryl Schwartz:

Thank you Matthew and good evening everyone. As Matthew said, my name is Cheryl Schwartz and I lead Takeda's U.S. Rare Disease Business Unit.

Thank you all so much for joining this evening.

Before we get started I just wanted to take a moment to acknowledge your feedback that the written communication we provided last month was surprising for many of you and even upsetting.

Our intent was to provide you with the latest timing estimates for NATPARA so that you and your physicians could make the most informed healthcare decisions, but I do want to personally apologize if that communication came across in any way as either insensitive or incomplete.

I also want you to know that we absolutely hear your frustration. We have read the letters and the e-mails that you sent us and I've heard that many of you have said that you felt hopeless and confused and angry that the issues that have led to the NATPARA recall have taken so much longer to address than really any of us had initially anticipated.

You've also clearly asked us for more information about the specific challenges that we're facing in bringing NATPARA back and why it's taking so much time. And some of you have also had questions about the cause of the ongoing shortage notifications for some of the patients in the Special Use Program and whether those two issues are somehow related.

And then lastly over the last couple of weeks we have been collecting your questions with the objective of sharing more information today on the multiple challenges that we're facing as we continue working towards bringing NATPARA back to patients in the U.S.

So, I want to introduce a few of my colleagues that are joining me here today who will help to address some of the questions that you have asked. First, is Tom Koutsavlis who many of you met along with me at some of our previous community calls. Tom is our Head of Medical Affairs and our Chief Medical Officer for Takeda's U.S. Business Unit. And Tom is also an emergency medicine physician and has treated patients with hypoparathyroidism.

So Tom is here really primarily here to address some of the questions that we've received regarding the Special Use Program and our recent notifications about some possible supply interruption.

So Tom and I are also joined today by Stefan Wildt our Research and Development Chief Technology Officer and Head of our Pharmaceutical Sciences Group.

So, we've asked Stefan to join us here today because a large group of people on his team in our research and development organization are working towards the goal of resupplying NATPARA to all U.S. patients. On today's call he'll explain the work that's being done by our device team as well as our regulatory, manufacturing and quality teams.

And then Stefan will then walk through two separate issues. We'll talk about quite a bit today that are contributing to the overall timelines of NATPARA's return. The first is, as you all know, the device component changes that we have been talking about since the beginning that are needed to fix the rubber particulate issue that originally led to the U.S. recall. And then equally important are some new issues that are impacting our ability to really ensure a stable and reliable supply of NATPARA and that's compounding our timeline.

And then finally I wanted to introduce you all to Tony Frangie who will be joining us just a little bit later. Tony is Vice President and Head of our Endocrinology business. And Tony and his team work every day on coordinating our efforts on NATPARA. He also works really closely with our patient services and our medical team on our Special Use Program support. And so, Tony has been really behind the scenes here also collecting and organizing all of the questions that you have been sending to us.

We've gotten some from the HypoPARA Association, by other groups that have submitted questions and by individuals through the e-mail address that we have provided. So our intent today is try to answer as many of those questions as possible kind of in the upfront comments because there was a lot of consistency in the questions that we received. But we're also going to make sure that we leave some time at the end, and Tony will help us with this, to address some additional very specific questions that you've asked in the recent days.

So with that I'm going to turn it over first to Tom, as I mentioned, to clarify the intent and the purpose of the SUP.

Tom Koutsavlis:

Thank you very much Cheryl. I appreciate that. I did want to say hello and welcome everyone. Unfortunately, I wish we could be doing this more in person. I know many of us have kept in touch over e-mail and text over the – over the past year. And again, looking forward to a chance when we do get together again and say hello.

I did want to cover some key points around the Special Use program and where we are, just to give you a little bit of background and walk you through some of the future-looking directions that we're taking as well.

So we've received several questions about the program itself, including why we can't open the program up to all patients who were prescribed NATPARA at the time of the recall. And I thought it might be helpful to remind everyone why the SUP was put in place, share some of the regulatory requirements around the program itself and give you some insights into the size and scope of the SUP to help give you a sense of the numbers and demands that it places on our manufacturing supply.

So, as probably many of you remember back in September 5th of 2019, Takeda issued a recall for all doses of NATPARA. So, that includes the 25, 50, 75 and 100 microgram doses. The recall occurred after discussions with the – with the FDA due to the potential risk of some rubber particles from the rubber stopper, the component that you know as the septum, entering into the cartridge itself at the time when it's punctured by the needle.

So during that 14-day NATPARA treatment period you could potentially have some rubber particles coming in through the septum when it gets punctured and that – those rubber particles may end up in the cartridge.

So, I wanted to pause and mention here that we've received many questions about the concept of the words voluntary recall. I think many of you may have read the words voluntary recall on the websites and how the FDA has described the recall that we have in play.

So just to clarify a voluntary recall is a regulatory definition for initiating a recall without the FDA requiring a filing of legal action or court proceedings. So, most drug recalls in the U.S. are labeled as voluntary recalls.

And even though NATPARA was classified as a voluntary recall, it was still an action Takeda was required to take as per the FDA code of regulations. And that's code of Federal regulations and there's a lot of detail that comes with that. So again, although voluntary is a term that's used in the statement itself, it is a recall that's required by the FDA.

So, at the time of the recall we focused on informing patients as quickly as possible that we were not longer authorized to commercialize NATPARA and that patients should seek their physicians immediately so they could be safely discontinued from the product.

We also reached out to physicians so patients like yourselves and providers could work together so that they can discontinue NATPARA as safely as possible considering the circumstances.

Now during the communication period that we had early on we started receiving concerns from healthcare providers that for a very few specific patients abrupt discontinuation due to the recall itself could lead to life threatening complications and that was definitely a concern that we heard from several healthcare – several of your healthcare practitioners.

And when the product itself is subject to a Class I recall federal law requires that all of the product be withdrawn from the market and the manufacturer can no longer make the product available to patients.

So, because of the concerns that we had from the healthcare community, healthcare practitioners, we reached out to the FDA and we worked on a solution of quickly putting together a very unprecedented program.

So, it's the first time this type of a program has been put into play. Where with the U.S. Regulatory Oversight we would give some healthcare practitioners the ability to request NATPARA for extraordinary cases where patients were facing life threatening consequences as a direct result of the discontinuation.

And that became known as the NATPARA Special Use Program, which you know today and which we sometimes refer to as the SUP. So this part, the part about the complications being a direct result of NATPARA discontinuation is particularly important because the SUP was intended to address only life threatening complications directly resulting from not having access to the product after the recall came in play.

So, in order to apply for the SUP your physician must initially assess whether you meet the appropriate criteria and then if so submit the applications to the Adjudication Committee with information evidencing the patient life threatening condition.

And again, the program was implemented with specific access and use restrictions to mitigate the risks associate with the recall and obviously to follow all of the particular requirement environment and the regulatory partnership that we had with the FDA.

So, it's important to note that as part of our agreement with the FDA to put the program in place a medical adjudication committee assessed and continues to assess to this day all SUP applications to ensure that they meet and continue – that they met and continue to meet the strict requirements of the program. The committee itself consists of both Takeda medical professionals and outside medical experts to ensure that we maintain the utmost of objectivity as we assess each one of these cases.

Now we originally estimated the program would be small and relatively short term while we were working on getting NATPARA back. But, of course, as you know and unfortunately the time to bring the product back has taken much longer than expected and today we actually have about 430 patients enrolled in the SUP in the U.S. So it's a fairly significant number.

Now according to the SUP requirements and remember the program is very regulated, strictly regulated with the FDA, NATPARA must be administered as single-use. So only one dose per cartridge and this is due to the potential risks of the device and the risk of the rubber particulate being pushed into the medication vial if the stopper is punctured repeated times with the needle itself. And that was of course the initial reason for the recall.

So what this means is that the SUP program while only meeting the needs today of about 430 patients requires twice as much supply of NATPARA as the entire patient population required prior to the recall. So two times as much supply. I know the numbers may not make intuitive sense but let me maybe walk you through just briefly some of the math that goes into how much product is needed at this point when we have to use a single cartridge as opposed to using a single cartridge 14 times to using a single cartridge only once.

So if I look at some of the numbers, if we think of before the recall itself there were about 2,800 patients using NATPARA and that equals about 72,000 cartridges per year. And if you look now at the little over 400 patients that we have that's about 150,000 cartridges per year through the SUP program. So we've doubled the demand of the supply in this smaller group of patients. And that's the unfortunate reality of only being able to use the cartridge once as opposed to 14 times.

So mention the significant supply demand of the SUP because any manufacturing delay we have can lead to a potential supply disruption for SUP enrolled patients. So this is why and you've seen in communications with you in the past, we monitor the SUP supply extremely closely and obviously the main goal is that we need to maintain the continuity of that supply for all of our SUP enrolled patients. So very critical that we keep a close eye.

So again a very unprecedented program and obviously there to help our most severe life threatening circumstances that some of you have faced personally. And I'm pleased that we're able to continue that with our FDA colleagues as we work closely with them.

So now I'm going to pass it over to Stefan who will be able to walk you through some of the work we're doing on remediating our device and other work on the manufacturing supply. So, Stefan, I hand it over to you.

Stefan Wildt:

Thank you, Tom. This is my first time meeting this patient community. I would like to thank you for giving me the opportunity to describe to you all our efforts. I represent an interdisciplinary team of dedicated Takeda colleagues and I want to assure you that we are working tirelessly to find a way to bring NATPARA back to you as patients.

So who is this team and how are we working? The team consists of colleagues from all parts of Takeda. Colleagues in development who work on the device and the drug product itself. Experts in manufacturing, quality and regulatory who are dedicated to the effort. In addition, we have specialists from distribution, medical and patient services. All of us are and have been focused on that NATPARA during this time and we remain highly committed to you, the patient community.

As you would expect, Takeda has dedicated significant resources across the organization to find a way to get that NATPARA back to patients. However, the journey has been much more difficult than we could have anticipated.

So what then is our approach? Shortly after the start of the U.S. recall our cross functional team went to work to first understand the specific regulatory concerns underlying the recall. Second, develop tests to understand the cause of the problem. And third, make a plan to evaluate remediation approaches to fix device components and address the concerns surrounding the recall.

Following this three-step process we tested a number of approaches that we hoped would allow us to quickly fix the device and return the product to patients. For example, Tom mentioned the rubber septum, we examined the rubber septum itself, here we focused on the possibility of fewer than 14 punctures. We also looked at the needle and just to give a sense for the level detail, we studied the way the needle twists through that rubber septum. We examined the rotation during needle insertion as well as several other variables.

This kind of testing takes time. It can involve designing studies that will appropriately address the questions from regulators. Conducting the studies, generating and analyzing sufficient data and compiling the reports and drawing conclusions. Then, if necessary, it can also include redesigning the studies and going back to the very first step.

When our early tests failed to identify a short-term fix to the device we had to pivot to our disappointment to work on more complex, robust and reliable solutions. It was at that time that we communicated the delay of at least one year in January 2020.

As we moved to other ideas to solve the problem we started all over again with the process I just described. We designed and conducted new tests. Tested the hypotheses followed by generating and analyzing data reports.

So where are we today in April 2021? At this time we believe we have developed an approach that will address the rubber particulate issue. Specifically, after a significant amount of testing we have changed two components of the device. We have introduced a new rubber septum and a new needle. We met with the FDA earlier this year to discuss the approach and work is ongoing now to generate data that the FDA has requested for a review and potential approval.

It might sound simple to replace a few components of the device however I'm hopeful that I have been able to give you a sense for the complexity of the task at hand that Takeda teams are dealing with here. We are encouraged by the progress we have made to date. At this point we're still a few months away from having generated all the data required for submission to the FDA.

Our latest assumption is that the data will be submitted in the third quarter of this year likely during late Summer. So, let's look ahead for a moment. What will happen next? Once our data and reports will be submitted the typical regulatory review timeline for this kind of submission can be four to six months. After that there are a few potential regulatory outcomes such as; one, regulatory approval; two, regulatory feedback that may have required minor or moderate changes to our approach or three, significant regulatory feedback that may lead to starting the process all over again.

So while we are optimistic that we have a potential solution, the timeline and outcome is unfortunately still far from certain. In the best case this process and current timeline would put an approval the fix of the device issue and return to the U.S. market at about 10 to 12 months from now. So this is important let me just restate that. In the best case we're looking at a return to the U.S. market with a fix of the device issue in 10 to 12 months from now. You have our commitment that we keep the community updated on our submission progress, timing and of course, the outcome.

At this point let me turn to a third topic, which is an emerging issue that arose while we were making progress with how to fix the device. This new issue has had an impact on SUP supply and also has the potential to impact our ability to provide consistent, reliable and stable supply in the future. To explain the issue I would like to take a step back and provide some information about NATPARA's manufacturing process.

First off, NATPARA is produced in what we refer to as batches which are based on dose strength, for example, 25 micrograms, 50, 75 and 100 microgram doses. During and after the manufacturing process every batch must meet predefined rigorous manufacturing and quality standards. These standards have been agreed upon with the FDA. Standards like these are put in place for approved medicines to ensure they're producible, reliable and safe manufacturing.

If a batch does not meet those rigorous standards for any reason, it cannot be released for patient use and is destroyed. One important part of the inspection and product release process is the visual inspection of the product; I'll explain that in a second. For NATPARA, the regulatory release requirements include that the drug product solution is clear and essentially free from particles.

The issue that occurred recently, which is impacting SUP supply for specific doses of NATPARA, is due to a higher percentage of batches that have not met the visual inspection requirement. So now let me move on to what we know. We know that the manufacturing process for NATPARA is particularly complex because it is a molecule that is extremely sensitive to manufacturing stresses, which can result in some product lots not meeting the quality standard established with the FDA.

We are currently actively working to understand one – why we are seeing an increase in the number of batches that do not meet our visual release criteria and why that's happening at a much higher rate than ever before, and two, why the manufacturing stress appears to be impacting the higher concentration doses, the 100 microgram dose at higher rates than the other doses?

In those batches that failed the visual inspection, we've seen clumping or cloudiness that shows the presence of protein particles. If we observe protein particles in the drug solution, the product may not meet the release specifications. And again, if it doesn't meet the regulated specifications for release, we cannot and would not supply it to patients.

Before I go further, it is important to note that all batches that have been released for any patient use have met quality standards agreed upon with the FDA, and are considered safe for use. I would like to repeat that. All batches that have been released for any patient use have met quality standards agreed upon with the FDA, and are considered safe for use.

Currently, our Takeda teams are working very hard to understand the root causes and identify potential solutions. This issue has led to the unpredictable supply interruptions for the SUP that we have been communicating over the past several months. We have already communicated the impact to the 100 microgram dose in the SUP, and we're watching other doses closely while we continue to work to address this issue.

One of the things we do to alleviate the risk of disruptions to any given dose for the SUP is generate a back-up or alternate prescription. We have done this for all patients on the 100 microgram dose already, and we're keeping an active watch out for our 75 microgram patients as well.

We will keep impacted patients and their healthcare providers informed. You may reach out to impacted patients with additional information as soon as this week. The upgrading challenges to SUP supply, these issues are also contributing to our latest projection that NATPARA's resupply timeline in the U.S. is at least 10 to 12 months from now, and Tom walked you through the stresses on our supply chain here.

Because even if we receive regulatory approval to move forward with fixing the device components, we have to ensure we have stable, consistent, and reliable supply for patients in order to bring the product back into U.S..

This brings me to the end of my section. I covered a lot of ground. I would like to thank you, also, on behalf of my Takeda colleagues, which I am representing here, for giving me this opportunity to describe the breadth of expertise of our dedicated team, share our efforts of expertise of our dedicated team with you, and our efforts today on overcoming the rubber particulate issues, and provide you with new information on the emerging Special Use Program supply challenge.

It is my sincere hope that I was able to clarify some of the complexities we face and address your questions. Thank you, again. Back to you, Cheryl.

Cheryl Schwartz:

Thank you, Stefan. So I know that was a lot of information, and I think, as you can imagine, it was really difficult to communicate some of this in just a letter, so I'm glad we have an opportunity to be able to explain it to you all in a little bit more detail. I'm just going to recap a couple of things because I know there was a lot thrown at you there, but Stefan's outlined really well that we're experiencing two separate but interdependent issues, right.

So we have the device component issue, for which we think we have a reasonable path forward, but then we also have the recent increase in those batches that are not meeting the criteria to release them for use, particularly the 100 microgram strengths which we're seeing more frequently.

And that issue is impacting our U.S. supply for both the SUP and for future resupply efforts. So some of the questions that we received about that is yes, they are connected and related to that underlying supply reliability issue. So what this means is that we have much to do. We still have to complete our regulatory submission with that proposed fix that Stefan just walked you through for the device components in the coming month.

And then we also need to get FDA's approval to our submission, and as you mentioned that is a roughly four to six month period, following that submission, that they take to review all of the data and information that we generate and come back with an opinion, and Stefan walked you through some of the potential outcomes of that review period.

And then lastly, we need to understand and address the recent manufacturing challenges we've experienced. So we can ensure we have a really robust device, as well as sufficient reliable supply continuity to come back to the market. I think that last part's really important because the last thing anyone of us wants to do is to come back prematurely and not have sufficient supply, and then cause more disruption for patients, especially given the risks that Tom walked you through that are associated with coming off treatments, and we know that many of you have experience that in the past.

So it's because of these three inter-related complexities that we're projecting the timeline that we shared with you of, at least, another 10 to 12 months from now before we think we can get back to the U.S. markets. And I hope that helps to explain a little bit of the why behind some of the timelines that we communicated last month.

So I know that there were also a variety of other questions that we also want to make sure we have time to get to. So I'm going to invite Tony Frangie to come back on here, and I'm going to turn it back over to Tony who's going to lead us through our Q&A session, and Tom and Stefan and I will kind of tag team some of the different questions that we have received, as I mentioned, through a variety of different channels. So Tony, I'm going to turn it over to you.

Tony Frangie:

Thanks so much, Cheryl, and thank you everyone for submitting your questions, either to us directly or through others. The first question we have is going to be for Cheryl. Cheryl, can you help us understand why you haven't shared more information about the extended timeline to resupply until now? To paraphrase, why hasn't Takeda been more transparent?

Cheryl Schwartz:

Thanks, Tony. So, where I started earlier this evening was that from the really – from the start, our main goal here with our communications has really been to make sure that you have all of the information that you need to make the best treatment decisions with your healthcare providers because we know you're dealing with a complex disease.

And so when we release information about timelines, it's because we want you all to have realistic expectations about the potential timing of the return of NATPARA to really guide all of those healthcare decisions. I will say that now I think we certainly realized that we missed the mark on striking the right balance in some of those communications, but I want to say again we're very sorry if this has led to additional confusion or concern.

That certainly was never our intent. Our intent is always to try to be as transparent as possible, but to be completely frank, sharing this kind of concrete information sometimes has been challenging, and that's for a few reasons. I think first, a number of issues that we've described to you today have really come up kind of real-time.

And often we've been in the midst of problem-solving mode, and it's really challenging to try to provide updates when we don't have enough information to not just give you updates but really clear solutions. And we didn't want to cause more confusion as we were working through the details and addressing the challenges that have arisen.

And then second, as you've heard so far this evening, the issues that we're talking you through have been pretty complex, both from a technical standpoint and also because of the interdependency issue and the way they affect one another. And so, we were really working through those interdependencies, again in real-time.

Every time that we were communicating with you all, we really believed that we were doing the right thing by prioritizing the information that you needed to inform decisions about your healthcare, but we do recognize the fact that you have requested and that you deserve greater transparency.

We hope that this session today is a step in the right direction to try to do better going forward and of course as we go through this process and we continue to kind of provide you with updates, we absolutely welcome your continued feedback on how we're doing and if there are areas that we need to do more, please do let us know.

Tony Frangie:

Thanks, Cheryl. The next question will be for Tom. Tom, this one relates to concerns around the recent supply issues. So the question is why can't Takeda just produce more NATPARA to ensure that patients enrolled in the Special Use Program don't experience supply interruptions?

Tom Koutsavlis:

Thank you for the question, Tony. And thank you – thank you to the community for the question and a very reasonable question as well. And indeed we have significantly increased supply. So in that sense we have actually increased supply to try and of course do exactly as you've described.

Unfortunately, despite maximizing our manufacturing capacity and producing a lot more product, we still find ourselves watching the SUP supply closely. Precisely with the reasons that Stefan mentioned. So I think he outlined why we're still struggling on the supply front.

So I know we've already communicated to you that we're projecting a supply shortage for the hundred microgram dosage strength and we're also keeping a very close watch on the 75 micrograms as well.

And it's possible we may be communicating with you later this week. So something we're keeping a very, very close eye on. I think until we identify the cause and can fix the manufacturing issues that we spoke about and that Stefan walked us through, producing more unfortunately doesn't adequately address the problem.

So as much as we've made more we haven't been able to address the issues that we're trying to manage. So we're committed to continuing to investigate the cause as we mentioned so we can address it as quickly as possible and obviously restore that product continuity for SUP patients.

I think one key that Cheryl mentioned and Stefan you mentioned as well, is that we absolutely want to make certain that we wouldn't bring product back to market until we know we can actually have product available for all of you.

And the priority obviously announced to make certain for those critical SUP patients yourselves that we absolutely are able to continue to provide product as much as possible. So that's our challenge and our push that the entire team is working on. So Tony, I hope that helped answer that question.

Tony Frangie:

No, thank you very much. And there is a broad team that's working on the issue for sure. Maybe Cheryl I can come back to you with the next question.

Cheryl Schwartz:

Sure.

Tony Frangie:

This is a more business and investment related question I think. Has the delay to NATPARA been caused by the financial liability of the overall program? For example, does the company benefit more from tax write-offs related to the SUP versus bringing the product back commercially?

Cheryl Schwartz:

Thanks, Tony. And while I appreciate where the question is coming from, I just want to be super clear that the answer to that question is no. The extended timeline to the U.S. resupply is related to the – all of these interrelated complex issues that we just shared with you tonight, it is unequivocally – it's not a question of profitability or priority focus, it's not a question of not supporting this product.

We absolutely understand the importance of this product and support its return to all of the patients who need it. I also just want to be super clear that there is not – there's no incremental tax benefit associated with operating the SUP. And operating the program is actually not treated as a charitable donation.

And ultimately our goal as a company is to deliver medicines to patients who need them. I mean especially patients like you who are living with rare diseases who have such high unmet need and who we've heard from all of you the impact that NATPARA has to your lives and the impact that not having NATPARA has to your lives.

So I just want to be super clear, there is no other kind of motive here. We have no intent of abandoning our efforts to understand and to address the issues that are impacting the timelines here. And we'll continue to do the work that's necessary, the work that Stefan and Tom and I have kind of talk to you through to do just that.

Tony Frangie:

Thanks, Cheryl. I'll ask this follow-on question to Tom. Tom, is there truth to the circulating rumor that Takeda is stalling with NATPARA until a competitor product such as TransCon PTH comes to market?

Tom Koutsavlis:d

Again, thanks for the question, Tony. And thanks to the community for sending in that question. So I think – let me start right off the bat and say unequivocally there is no truth whatsoever to any of these rumors.

I think many of you now I've gotten to know more personally and many of you have gotten to know me and I appreciate having had the opportunity to work with you for such a long time.

I can tell you that everything in our power, everything in our being has been to try and fix all of these problems and get the product back to you as quickly as possible. So rest assured that this is a full speed endeavor for many, many people.

You see the four of us on screen right now and I can you there are hundreds behind us that are helping to try and move this forward. So that way I can – I can assure you with certainty that there's absolutely no truth to any of those rumors. Our goal is to absolutely help the community as much as possible and I think I shared with you my own personal connection to hypopara.

Look, we absolutely know that there are other products in clinical development to treat patients for chronic hypopara and I think that's a wonderful thing. We very much support innovation and availability of treatment alternatives, especially in the space of rare and serious diseases like hypopara where there are limited options and there are not a lot of other things for patients and their families.

So as a physician myself I'm encouraged to see other things being developed and R&D really pushing in that direction. We've also been very privileged to share some calls and meetings and congresses with you with other companies as well who are working forward – looking forward to working on other treatment alternatives.

And again, it's a very exciting time for us in the community. So that piece is very critical. Now at the same time we also understand the risk of drug development and commercialization well enough to know that we cannot depend on all of those other options as potential solutions.

So we've seen what we've gone through obviously with NATPARA and we know that until a product is approved and on the market, we don't quite know where some of the other R&D will head to. So critically important that regardless of anything else that's happening with other products and other R&D that's coming, we have to keep our focus on addressing the challenges of NATPARA and making sure we get NATPARA back to you. I think that's critically important.

Tony Frangie:

Thanks, Tom.

Tom Koutsavlis:

Thanks, Tony.

Tony Frangie:

All right. Cheryl, I'm going to come back to you again. We've received several questions about the difference between the U.S. and markets outside of the U.S. For example, some patients have asked why the product is still available for commercial use in Europe while others have asked if Europe has the same supply issue that we are currently experiencing with the U.S. Special Use Program.

Cheryl Schwartz:

Yes, we have definitely heard lots of variations on the question and I think first-off we definitely want to acknowledge that we understand that it definitely can seem confusing or frustrating that this product is available in Europe. It's called NATPAR in Europe and that it's still available for patients in Europe.

The thing – the first thing to note is that the drug product is the same. And we did provide the same information to all the regulatory agencies where NATPARA or NATPAR as it's called in ex U.S. are available.

In the case of NATPARA, the U.S. regulatory authority, the FDA did request a voluntary recall, which we talked about earlier. While that option was not requested, I think as you all know by other regulatory authorities, including the European Medicine Agency.

So but in terms of the current supply interruptions, the interruptions for U.S. patients that are receiving NATPARA through the SUP are really influenced by the high number of cartridges that are required in the U.S. because of the single use requirements.

So that was the map that Tom shared with you a little bit earlier. And when you compare that to Europe the number of cartridges that are required for that population is actually much lower since we can use all 14 of those does in each cartridge for patients.

So just to give you a little bit of again, kind of an order of magnitude of what we're talking about here in Europe is there is just about as many patients outside of the U.S. on NATPARA as in the current U.S. SUP program.

So I think that's a little bit of a – kind of a misperception that exists was that – is that Europe population is the same – was the same as the pre-recall U.S. population. So it's a much smaller number. And so therefore one single release batch, we talked about batches earlier of product in Europe basically supplies enough cartridges with 14-day use to last a full year.

So one batch in Europe lasts a year for the number of patients that are currently taking it there. But by contrast with the single use requirements of the cartridges that are used in the SUP, that same one batch basically with the same number of cartridges because we're only using it one time, only provides about three to five weeks of supply coverage for SUP patients.

So that's why even though the underlying issues are the same, that's why we don't have the same consideration both on the regulatory front and on the supply front. And I know that's definitely something that we've received a lot of questions about and it can be confusing.

But I do think it just helps to understand the order of magnitude and really to just kind of dimensionalize what it means when you're using that one versus that 14-dose, and it's certainly a huge impact in terms of the supply implications.

Tony Frangie:

Thanks, Cheryl. Stefan, I didn't forget you – that you're on the line, so the next one is for you. This one is another question we received a few different variations of, so hopefully I've captured it correctly. Why haven't we offered patients a different device, or an alternative delivery option while we're working to fix the current device components of NATPARA?

Stefan Wildt:

Yes, so thank you for the question. Well, we want to assure you that since the beginning of the recall we've had a large cross functional team that spans regulatory, manufacturing, quality device, medical, and many other areas of expertise dedicated to trying to understand and address these issues.

So this team, as I described before has explored many different options, and just to be safe we also have engaged external consultants to pressure test and validate our findings.

And some of the options we explored were not technically feasible, while others are possible but would require extensive clinical or as we refer to them, human factor trials which are a regulatory requirement for medical devices to demonstrate that they are effective with a specific drug and in a specific patient population.

So you can see how all of this then can add also to – and result in even longer regulatory review timelines than the plan we outlined today. So we believe that the plan we've been working on offers the greatest likelihood of success and the fastest timeline, otherwise we would have picked something else.

That does not mean that we do not have other options that we are working on in parallel, but at this time we are focused on the approach we shared tonight which involves a new rubber stopper, and a new needle.

Thank you for that question.

Tony Frangie:

No, thank you, Stefan. We received it in a lot of different ways, whether it was can you mix NATPARA, draw out the doses into separate vials? Could you use some kind of pump to replace the device? But I think your answer is really appreciated there. So all of these things have been considered.

So Cheryl, I think this is our last question. So I'd like to come back to you with it. We received

...

Cheryl Schwartz:

Thanks.

Tony Frangie:

... several questions here as well in a few different formats – or forms. Really about our level of commitment to hypoparathyroidism as a category, to the patient community, and to bringing NATPARA back in the U.S.

Cheryl Schwartz:

Thanks, Tony. Again, I totally understand why we keep getting this question because I think that at the end of the day the result isn't yet where you all need it to be, right? And so it's a natural question, I think, to ask.

I want to assure you first and foremost that our commitment of Takeda to bringing NATPARA back, and to all of you – to the patient community, to your families remains really, really strong. I want to make sure that you understand that there is not a day that goes by that we don't talk about this program, that we don't work on this program.

The team has really kind of looked under every stone and I just want to reinforce kind of one other point which is that – that hasn't come up tonight, which is about Takeda itself as an organization.

And you know, we have something that we use as our kind of, our guiding principles, our core set of values, basically that we use to drive decision making at our company, we call it PTRB and it stands for patient trust reputation and business.

And really, that's how we make decisions, we start with patients, we think about trust, we think about reputation and then and only then do we think about business. And so the P in PTRB comes first really for a reason, and that's because all of us at Takeda are really committed to putting our patients first.

And so, really whenever we talk about NATPARA we always start with a discussion of all of you and the impacts of what's happening to you as we go through this process.

For example, Tom shared earlier some of the background that led us to propose the special use program to the FDA in the first place. When we set up the SUP and we continue to provide NATPARA to the enrolled patients in that program, which I said, there's now 430 patients that are enrolled that – who come with a direct request from healthcare providers to really meet critical patient needs.

And while that program was originally intended to address a short-term need, that would provide a bridge until we had NATPARA back, we've definitely remained committed to continuing the SUP as long as we have that supply, and that program is under very strict regulatory oversight.

So if obviously we can't predict exactly what the future holds, but it's certainly something that we talk about – again, every single day about the importance of that program, and we monitor it incredibly closely. It's also with the patient community in mind that we continue to commit the necessary – the time, the money, the resources, to bring NATPARA back to the U.S.

And so, I just want to assure you that that is happening on an ongoing basis. One other thing that we've heard quite a bit in terms of questions that's kind of related to the question you're asking Tony, and I know you've heard this one as well.

If Takeda is planning to sell NATPARA, and the answer to that is again, no. When Takeda acquired Shire and NATPARA came with that, we made the decision to continue to commercialize NATPARA as Takeda. And that decision was based on patient need.

We absolutely understand the critical nature of NATPARA to those who are suffering in this community, and we don't intend to sell it off now, or abandon our ongoing efforts that we've been committed to.

So I think that we can certainly all agree that we had hoped that the road to resupply in the U.S. would have been much shorter, and with far fewer curves and bumps. But we have stayed the course because we are committed to working to get NATPARA back to all of you.

So I hope that does help to address it. I think ultimately, it's going to come down to us continuing to prove to you that we're working on this, but it is something – as I said, we are very, very committed as an organization.

So maybe with that, Tony, thank you for the questions. I hope that we've been able to address many of the questions that you sent us. Before we close the call today, I do want to take time to thank you again for joining today, and let you know how much we appreciate all of your feedback. Sometimes it's hard to hear, but it's important to hear – and so we really, really do appreciate that.

And although, I hope that we've answered a lot of the questions that you sent us. I know that this new information might help you to understand why the delays are happening, but it certainly does not alleviate the suffering of the community, or help those of you who really continue to be so impacted by this terrible disease.

We said a few times tonight, we talked about all the different teams that are working on fixing this issue that are impacting our resupply timelines. And I know when you see our communications, and you see these letters that come out, or you see those of us on the screen today – you might just see like big corporation.

But I want you to know that Takeda is made up of all of these people. You know, the people that you see here today, the people on Tom, and Stefan, and Tony's team whose job it is to develop and bring medicines to patients who need it.

And you know, most of us got into this work because we're either scientists, or physicians, or actually a lot of us who work in this area were drawn to the field because we have direct personal experiences with rare diseases ourselves in our families. And so we do have a personal investment and commitment of people as well – above and beyond Takeda as a company.

So, kind of in closing today, above everything else that we've talked about today, we want you to know that we understand what this medicine means to you and to your families, and again, I want to just let you know that we remain committed to you, and to continuing to do everything in our power to bring NATPARA back.

So with that I'll thank Tom, Stefan, and Tony for joining me here today and for helping to answer, hopefully some or many of your questions. And a huge thanks to all of you for joining us this evening. We commit to staying in touch, we hope that you'll commit to keeping on giving us the feedback that we need to do better, and we hope to be able to provide you with additional updates soon.

So, thank you very much and hope you have a good evening.

Tom Koutsavlis:

Thank you.

Stefan Wildt:

Thank you.

Operator:

Thank you again for joining us today. This concludes today's web conference, you may now disconnect. Have a good day.

Thank you for listening to the recording of this call.  Please stay on to hear Important Safety Information about NATPARA.

Important Safety Information

What is the most important information I should know about NATPARA?

Warning: Possible bone cancer (osteosarcoma).

  • During animal drug testing, NATPARA caused some rats to develop a bone cancer called osteosarcoma. It is not known if people who take NATPARA will have a higher chance of getting osteosarcoma. Tell your doctor right away if you have pain in any areas of your body that does not go away, or any new or unusual lumps or swelling under your skin that is tender to touch.
  • NATPARA is only available through the NATPARA Risk Evaluation and Mitigation Strategy (REMS) Program. The purpose of the NATPARA REMS program is to inform patients about the potential risk of osteosarcoma associated with the use of NATPARA. For more information about this REMS program, call 1-855-NATPARA (628-7272) or go to www.NATPARAREMS.com.

NATPARA may cause other serious side effects, including:

High blood calcium (hypercalcemia)

  • NATPARA can cause some people to have a higher blood calcium level than normal.
    • Your doctor should check your blood calcium before you start and during your treatment with NATPARA.
    • Tell your doctor if you have nausea, vomiting, constipation, low energy, or muscle weakness. These may be signs that you have too much calcium in your blood.

Low blood calcium (hypocalcemia)

  • People who stop using or miss a dose of NATPARA may have an increased risk of severe low blood calcium levels.
  • Tell your doctor if you have tingling of your lips, tongue, fingers and feet, twitching of face muscles, cramping of feet and hands, seizures, depression, or have problems thinking or remembering.

Tell your doctor right away if you have any of these signs and symptoms of high or low blood calcium levels.

Who should not use NATPARA?

Do not use NATPARA if you are allergic to parathyroid hormone or any of the ingredients in NATPARA.

What should I tell my healthcare provider before using NATPARA?

Before you start using NATPARA, tell your doctor about all of your medical conditions. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of NATPARA?

NATPARA may cause serious side effects like allergic (hypersensitivity) reaction, including anaphylaxis. Tell your healthcare provider or get emergency medical help right away if you have any of the following symptoms of an allergic reaction:

  • swelling of your face, lips, mouth, or tongue
  • breathing problems
  • fainting, dizziness, feeling lightheaded (low blood pressure)
  • fast heartbeat
  • itching
  • rash
  • hives

The most common side effects of NATPARA include: tingling, tickling, or burning feeling of the skin, low or high blood calcium, headache, nausea, reduced sense of touch or sensation, diarrhea, vomiting, pain in joints, too much calcium in urine, and pain in limbs.

These are not all the possible side effects of NATPARA. For more information, talk with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see Prescribing Information, Medication Guide, and Instructions for Use available on NATPARA.COM.

Thank you!

Latest Updates

Sorted by Most Recent

Media Statement

October 4, 2022
Takeda announces that it will discontinue manufacturing of NATPARA at the end of 2024
Download PDF version of Letter to Patients

Hypoparathyroidism Community Call

March 31, 2022
Information for upcoming patient community call
Download PDF version of Letter to Patients

Letter to HCPs

March 23, 2022
Prior Approval Supplement Update
Download PDF version of Letter to HCPs

Letter to HCPs

December 20, 2021
2021 Year-End Update
Download PDF version of Letter to HCPs

Letter to HCPs

September 15, 2021
FDA Regulatory Filing Update - Prior Approval Supplement
Download PDF version of Letter to HCPs

Letter to HCPs

July 12, 2021
Special Use Program Supply Update 6
Download PDF version of Letter to Patients

Letter to HCPs

June 14, 2021
Special Use Program Dosing Plan
Download PDF version of Letter to Patients

Letter to HCPs

April 12, 2021
Recall Update 2
Download PDF version of Letter to Patients

Letter to HCPs

March 31, 2021
Recall Update
Download PDF version of Letter to HCPs

Letter to HCPs

February 5, 2021
Special Use Program Supply Update 5 - Resolved
Download PDF version of Letter to HCPs

Letter to HCPs

December 22, 2020
Special Use Program Supply Update 4
Download PDF version of Letter to HCPs

Letter to HCPs

December 16, 2020
Special Use Program Supply Update 3
Download PDF version of Letter to HCPs

Letter to HCPs

November 16, 2020
Special Use Program Supply Update 2
Download PDF version of Letter to HCPs

Letter to HCPs

October 20, 2020
Special Use Program Supply Update
Download PDF version of Letter to HCPs

Letter to HCPs

January 21, 2020
Update on timeframe for NATPARA® (parathyroid hormone) availability
Download PDF version of Letter to HCPs

Letter to HCPs

November 21, 2019
Commitment to Hypoparathyroidism Community
Download PDF version of Updated FDA Classification

Updated FDA Classification

October 9, 2019
FDA classifies NATPARA recall as a Class 1 recall requiring return of all unused product
Download PDF version of Updated FDA Classification

Special Use Letter for HCPs

September 24, 2019
Additional details about the NATPARA Special Use Program
Download PDF version of Letter to Patients

Special Use Program

September 24, 2019
Takeda announces NATPARA Special Use Program in the US
Download PDF version of Special Use Program

Recall Information

September 5, 2019
Takeda issues US recall of NATPARA due to the potential for rubber particulate
Download PDF version of Recall Information

NATPARA Special Use Program

Takeda has worked with the FDA to develop a Special Use Program for NATPARA. The program’s intent is to allow access to the drug by patients facing severe health consequences due to the inability to receive NATPARA. Physicians can submit a request to Takeda explaining the patient’s severe and/or life-threatening medical situation. An adjudication committee will review the requests on a case-by-case basis. Physicians who believe they have a patient meeting this criteria should email Takeda at NatparaSpecialUseProgram@Takeda.com. Download the PDF for full details.

Get Details

NATPARA®, OnePath® and Q-Cliq are trademarks or registered trademarks of Shire, a Takeda company.