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. For more details, read our PDF. Be sure to bookmark this page and check back often for the latest updates.
Listen: Community Call
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.
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.
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.
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.
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.
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.
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?
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.
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?
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.
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.
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?
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.
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?
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.
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.
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.
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?
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.
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
... 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.
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.
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
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.
Hypoparathyroidism Community Call
Letter to HCPs
Letter to HCPs
Letter to HCPs
Letter to HCPs
Letter to HCPs
Letter to HCPs
Letter to HCPs
Letter to HCPs
Letter to HCPs
Letter to HCPs
Updated FDA Classification
Special Use Letter for HCPs
Special Use Program
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