Agios Pharmaceuticals, Inc. (AGIO) Earnings Call Transcript & Summary

All right. It's 7:00, so let's go ahead and get started. Thank you, everyone, for joining our approval event today. We will -- we have some prepared remarks. We'll go through our label and commercial plans. And then at the end, we'll have time for Q&A. [Operator Instructions] So Jackie, I will turn it over to you.

Thank you, Holly. Good early morning, everyone, and thank you for joining us early this morning. It's a very exciting time for us at Agios today as we got our first genetically defined disease indication drug approval yesterday, and we're just thrilled with that and look forward to speaking with you about it today. Just as a reminder, less exciting, but necessary, this presentation will include forward-looking statements. Before we get started with the specifics of today's -- or yesterday, actually, announcement I want to start with one of the key ways that we differentiate ourselves at Agios with what we do. Clearly, we believe we have differentiated science and a very strong track record. But in addition to that, it's through the connections that we form with all of the people that we work with that includes internally and across our different functions, which is why we're so successful with how we discover, develop and then bring drugs to market. It's also with health care providers and other external parties. But the group that I want to speak about today are patients. We formed very strong connections with the PKD patient community over the many years now that we have been studying mitapivat for pyruvate kinase deficiency. And so it's really special to us to be able to celebrate our first approval for a genetically defined disease for one that, until yesterday, had no approved treatment options. And it is our third drug that we have discovered and developed internally at Agios which speaks to our strong track record and history, especially for a company of our size. We've learned over time that we can be even better and advance the promise of our science to develop great therapies if we listen to patients, connect with them and work with them to better understand their diseases and how they can potentially be treated. The pyruvate kinase deficiency community has been a key contributor to the news that we had yesterday in the approval milestone for mitapivat. They participated in our clinical trials over many years now. Mitapivat is a drug that's been in the clinic for over 7 years. They also participated in our natural history study. And these patients have been willing to maintain a continuous dialogue with our team to help us understand their lived experience with their disease and providing us very meaningful feedback, both on our clinical as well as our patient support and other commercial programs. So without you pyruvate kinase deficiency patients, this approval would not be possible, and I just want to thank all of you for everything that you've done in your collaboration with us at Agios. When we talk about just about being the pioneers and the leaders in PK activation, we say that from the basis of a tremendous amount of substance, some of that is shown on the slide up on the screen here. I'm not going to go through all the details on this slide, but it is designed to give you an idea of our pivotal clinical programs and our pediatric program will move into [ pivotal ] status this year as well. So we'll be adding to that. And we've studied mitapivat across 3 diseases now with the approval of PKD and a tremendous amount of publication that we've done on a PK activation over the years. And we're extremely proud of this. And there are a lot of firsts that Agios has brought to this area, and you can refer to those on the slide as well. The leadership that we have in PK activation has now materialized into the first approved PK activator. I'm very pleased to share with you the brand name and logo for PYRUKYND or mitapivat as you all know it. So here it is on the screen. And with that, I'm going to turn it over to Sarah, who will review the details from our label, and after that, Richa will talk to you about our launch plans and commercialization of PYRUKYND.

Thanks, Jackie. So I'm excited to be able to share with you the highlights of the U.S. prescribing information today. So of course, over the last 8 months, we've had a very productive collaboration with the agency, and this application was reviewed under priority review and now we're sharing the label. So PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency. So this label does not include exclusions for genotype, transfusion needs or hemoglobin range, and so we're very, very pleased with that. So the dose will -- it's very similar to what happened in the clinical trial. So the starting dose for PYRUKYND is 5 milligrams twice daily and then there is a dose escalation to gradually increase hemoglobin through sequential steps. So from 5 to 20 milligrams twice daily and then 50 milligrams twice daily, which is dependent on the review of the hemoglobin parameters. And then if by 24 weeks, no benefit has been observed and that is also defined by the totality of the data of hemoglobin and hemolysis laboratory results or transfusion requirements, then it's recommended to discontinue PYRUKYND. Warnings and precautions. So we have an acute hemolysis warning in the label that is based on those 2 cases of acute hemolysis that we've seen in the DRIVE PK study. And so -- it's -- when being on this therapy, I want to discontinue, its recommend to avoid interruption or abrupt discontinuation and to a dose taper. So the safety and the efficacy data that you'll see in the USPI are reflective of the ACTIVATE and ACTIVATE-T data. So in the efficacy section, it starts with the ACTIVATE data. So it calls out our primary endpoint. So 40% of patients achieved a hemoglobin response in PYRUKYND versus 0% in placebo. Then we have demonstrated statistically significant improvements on our secondary endpoints, and that's also reflected in the label. And then we're also very pleased with the PRO data that are described in the label, which highlights that we improved jaundice, tiredness and shortness of breath as measured via the pyruvate kinase deficiency diary. Serious adverse reactions that occurred in the trial are also summarized in the label. So in ACTIVATE, we had one patient experiencing atrial fibrillation, one patient experienced gastroenteritis, one had a rib fracture and musculoskeletal pain. The most common adverse reactions, which includes lab abnormalities in patients with PK deficiency, were estrone decrease in males, increased urate, back pain, estradiol decreased and arthralgia. And then we also have, of course, the ACTIVATE-T data because we have efficacy data across the entire population with and without transfusions. And so the ACTIVATE-T data summarizes our experience in regularly transfused patients. So 33% of patients treated with PYRUKYND achieved a transfusion reduction response, which is defined as a 33% reduction in comparison to the historical transfusion burden, and 22% of patients were transfusion-free. And then the adverse reactions are summarized in a sentence, highlighting that the pattern was very consistent with what was observed in ACTIVATE. So of course, we're very pleased with where we are today, but we realize we have a lot of work to do. And so we're -- 2022 is going to be an execution year for us. The review in Europe is ongoing and is on track. Of course, with this adult benefit risk profile that we have generated across ACTIVATE and ACTIVATE-T, we're now very excited to also move forward in our pediatric program with ACTIVATE Kids and ACTIVATE-Kids-T. And then, of course, alpha and beta thalassemia and sickle cell disease with mitapivat as well. And we really are also equally excited by 946 in MDS, so 2022 is a big year. And then lastly, of course, based on our approval here and all of the data we've generated, we really have a tremendous amount of confidence in PK activation as a mechanism -- as a therapeutic mechanism across all of these different disease spaces. We're excited to continue to generate data across our programs, and we'll continue to share that with you over time. So with that, I'm very excited to be able to hand it over to Richa to talk about our commercial launch.

Thanks, Sarah. The commercial team is very excited by the launch of PYRUKYND, the first and only approved treatment for adults living with pyruvate kinase deficiency. Our commercial strategy, which is informed by a deep understanding of the patient provider experience navigating to this disease has 3 pillars: enabling accurate diagnosis; ensuring eligible patients are prescribed PYRUKYND; and ensuring patients have access to treatment and can stay on therapy. As we've mentioned before, a lot of our prelaunch efforts were really focused around identifying patients. We did this through a variety of different channels. We [ data ] claims-based analysis. We use ICD-10 codes, mind electronic health records. We also have a partnership, as you've heard from us before, with 23andMe. We continue to add ID patients also with genetic testing efforts through PerkinElmer, which is coupled with genetic counseling. And then over time, we've also continued to raise disease awareness through our disease education efforts through myAgios as well as Know PK deficiency. We want to ensure that we are continuing to elucidate the burden of disease and creating an urgency to diagnose as yet undiagnosed pyruvate kinase deficiency patients because we know that diagnosis rate currently is quite low. These efforts, we expect will continue even in our post-launch world. As Sarah mentioned, we have very strong data from our pivotal registration trials with ACTIVATE and ACTIVATE-T. So we want to use that data, educate the patients and providers on this data, to highlight the value that PYRUKYND can bring to adult patients living with pyruvate kinase deficiency, not only given that it's the only approved therapy for this disease, but it also has the potential to change the course of chronic hemolysis, which is a hallmark of this disease. So we want to be able to use this clinical data and ensure that all eligible patients have the opportunity to benefit from PYRUKYND. We've designed an access and pricing philosophy to ensure access for our drug and it has 4 pillars: creating meaningful outcomes for patients, staying connected with the communities, emphasizing transparency and ensuring sustainability to help even more patients in the future. With this philosophy in mind, we've determined an average annual wholesale acquisition cost for PYRUKYND to be $334,880. We're also committed to not raising the price for 5 years. We've also designed a very robust patient support program called myAgios. myAgios will serve as a single point of contact for the patient as they navigate their treatment and is staffed by 2 clinically trained professionals, patient support managers with over 30 years of rare disease experience. They'll be working very closely with the patient one-on-one and customizing the program according to their needs. The offers that this particular program has includes disease education, which is connecting the patient with a broader PK deficiency community, helping them navigate conversations with their health care provider and helping them cope with their disease. This service is available to all patients irrespective of their treatment. We are also providing insurance coverage support where the myAgios patient support manager will work directly with the patient and the insurance provider to ensure access to treatment. For commercially insured eligible patients, we have a $0 co-pay program. And we also have free drug programs for those that might have gaps in their insurance coverage. We hope that this holistic approach to patient services results in a seamless experience for the patient. As we've indicated before, in the U.S., we anticipate approximately 3,000 patients are living with pyruvate kinase deficiency. Of those, 30% are diagnosed today. We're very excited about the approval, which is for the 80% of adult patients living with pyruvate kinase deficiency. Of these, about 9% to 15% have the double non-missense mutation, and about 30% of them have a hemoglobin greater than or equal to 10 grams per deciliter. As Sarah pointed out, these are not excluded per the label, which we're very excited about. But because they were not included in our pivotal registration trials, it is possible that some payers might impose some restrictions. The way we've designed our access program will allow for the broadest possible access so that patients who need our therapy and are eligible for our label have the opportunity to do so. We anticipate, based on our market research, that physicians will want to trial PYRUKYND in the majority of the adult patients. We expect reauthorization from a payer perspective in every -- around every 3 to 6 months, and Sarah has already covered how the response is worked out in our clinical studies. From payer standpoint, we've been having conversations with them prior to approval. Holly, if you could go to the next slide? Helping raise awareness about the disease as well as around the burden of disease, and all of these conversations have been quite positive. As a reminder, we do expect that early on, reimbursement will be through the medical exception process, which can take about 6 to 12 weeks until the drug gets on formulary. Optimal coverage for the commercial patients, which forms the majority of our covered lives here is expected to take about a year with Medicare and Medicaid lagging behind. We have a very seasoned field team with a lot of rare disease experience, and they've been in place since last year and this group of individuals has been working very closely both with each other but also with a broader PK deficiency community, establishing a very, very strong knowledge base and connections that will propel us towards success in this launch. This one Agios' team is formed with 6 medical science liaisons, 3 clinical nurse educators, 18 hemolytic anemia specialists, 2 patient support managers and 3 national account directors covering the U.S. nationally. The story, however, does not end there. We're very excited about our first launch in genetically defined diseases with PYRUKYND. The strong foundation that we've built and that Jackie and Sarah both referenced in their remarks. In PK activation and the lessons that we learned from this particular approval will hold us in really good stead for future hemolytic anemia indications like thalassemia and sickle cell disease. So the future is looking very promising, and we're very excited about that. With that, I'd like to hand it back over to Holly.

Thanks, Richa. [Operator Instructions] All right. So we'll start with a question from Greg Harrison at Bank of America. You mentioned that the diagnosis rate could increase due to disease-modifying drug becoming available. Where do you think it is now and where could it go? What are you expecting as far as the cadence of the increase?

Yes. So diagnosis rate today, we anticipate based on all of the work that we've done, is about 30%. Based on our understanding of other rare disease analogs and the evaluation of that market landscape, we think it can go up to as high as 70%, which is sort of seems to be the peak for rare diseases. It can take anywhere from 2 to 5 years, and there's a lot of factors that go into it, including how quickly, you can ID patients, how fast formulary coverage works. And then in our situation, we are also -- continue to monitor how the pandemic evolves. So all of those factors should determine the ramp, but that's -- the peak -- we're pretty confident about the peak based on everything that we've seen thus far.

Question from Anupam Rama at JPMorgan. Thinking about diagnosis rate, you said that it was 30% at launch, are there comps we should be thinking about for trends? Also, is it 30% in the EU? And is it similar trends in terms of time?

The trends are pretty similar between the U.S. and Europe. The patient population is also pretty similar between the U.S. and Europe. I think the one difference with Europe is that pricing and reimbursement takes longer. So from that perspective, the ramp can take a little bit longer because each individual market works a little bit differently. So in that context, it's pretty similar between the 2 in terms of diagnosis rate, but the ramp can take a little bit longer because of the pricing and reimbursement.

Question from John Newman at Canaccord. You saw good responses at low doses in DRIVE PK, what portion of patients do you think will only need the 5-milligram dose?

So just in DRIVE PK, we actually have 50 milligrams as the lowest dose, which is consistent with the maximum recommended dose in our current label. And so in ACTIVATE, we had a dose escalation of 5, 20, 50. The majority of patients have to go to 50 milligrams. So we are anticipating that, that would be the same.

Question from Alethia Young at Cantor. Can you talk about any notable differences between the discussions with the EU filing versus the process in the U.S.?

So the process in the U.S. requests for -- questions can come in at given any given time. There are very structured meetings along the review timeline that everything occurred on track there. And the questions came and we answered them as was requested. In the EU, it's much more structured in the sense that you get a bolus of question on specific date, and you have to answer those questions within a specific timeframe. So there also, everything is following the procedure as anticipated. We answered our day 120 questions, that's what it's called, on track. And so everything is proceeding as we've anticipated.

Great. A question from Mike King at H.C. Wainwright. What percent of patients are on CYP3A4 modulators? Are you using flat pricing amongst the different doses?

So for the first question, there are obviously some patients on these drugs. We have patients on these drugs in our clinical trials, but it is a minority of patients. So that's what we're anticipating as well for the market space. Now we -- for the drug-drug interactions there are very clear instructions in the label in what to do, what we recommend to do for each situation.

And then in terms of pricing across the doses, it's the same. So it's flat pricing.

Okay. Question from Marc from Cowen. What is the payer mix you would expect for the adult PKD population? What does this mean for likely gross-to-net discounts? And how does this shift as you eventually add pediatrics to the label?

Yes. So the payer mix is largely commercial, so about 55% with Medicare and Medicaid forming about 30% and then you have a mix for the remainder. And in terms of gross to net, we are not providing that information at this point and pediatrics, we can get back to you on that one. I'm not exactly sure how that would evolve.

Question from Kennen MacKay at RBC. The label recommends discontinuation of treatment at 24 weeks if no benefit is seen by hemoglobin, hemolysis or transfusion burden. How do you think the benefit will be defined by physicians and by payers? Should we assume similar to patients not achieving a response by the ACTIVATE and ACTIVATE-T criteria or is it more liberal?

So it's actually more liberal and that comes -- that criterium actually was put into place to allow for physicians to assess the totality of the data. So that's why it's not only hemoglobin, but also, for instance, the hemolysis parameters that are called out in that discontinuation criteria. And that is because we did see some patients reaching a threshold of the primary endpoint post 24 weeks, but we saw signals of improvement on, for instance, the hemolytic parameters before -- right before 24 weeks, and that's where that timeframe comes from.

Okay. Question from Danielle Brill at Raymond James. How many patients are in the OLE? And how quickly will they roll over to reimbursed drug?

So we have still a vast majority of patients actually in our open-label extension study. So for DRIVE PK has been stable for a while, and those patients are continuing. So in totality, the exact number, I think we're still around 70 patients in the open-label extension, but we can verify and check in that exact number. We will continue the open-label extension studies because we want to collect or continue to collect long-term efficacy and safety data. As you know, we've presented the first long-term view of the people in the extension study from ACTIVATE and ACTIVATE-T and have highlighted the impact on iron metabolism there. So we are continuing to collect data, both from an efficacy perspective and a safety perspective. So those patients will not be rolling over to commercial drug.

Question from Salveen Richter at Goldman. When in 2022, could you start recognizing revenue?

So I think we'll have to -- it will be limited in the first couple of quarters as we talked about because it will take a little bit of time before reimbursement kicks in, and it will be all through the medical exception process. So it all depends on how quickly things turn, how quickly we get the first script, how quickly it gets reimbursed. So I think we'll have to wait and see for the first couple of quarters, but it can -- I would say the first quarter since we're well into it, probably limited and then second quarter on, you can start seeing some movement.

Can you talk about the impact of reproductive hormone abnormalities observed in the adult trial, on the pediatric trial enrollment and potential label?

Sure. So as highlighted in the label right now, those are laboratory changes not linked to any clinically significant event that made it into the ADR table. So we, obviously, now based on the benefit-risk observed in the adults are moving forward in the pediatric population, and we'll be continuing to collect this data. And all of our efficacy data, other safety data over time in the pediatric population to update those sections of the label. The fact right now is that the majority of those changes that we've observed in the label have remained within the normal limits, the labs as presented are shift table. So if you get a point at a specific time point you were collected there. And we're going to collect that same data in the peaks. This is why you have to do pediatric trials for any drug, right? You can't assume that pediatric patients are mini adults and both from efficacy and safety, and that's why we're doing this program. We're very excited about it. I mean with the data that we have, it's really -- it's really great that we're about to start that program.

Another question from Greg Harrison. How do you expect the pricing to transfer to thalassemia and potentially sickle cell disease? Can you talk about your pricing approach with respect to the label expansion strategy?

So the way to think about price, at least based on all the research that we've done, first, we'll have to look and see how our clinical trial data reads out. So we've always taken a very holistic approach to price, and we expect to do the same with both thalassemia as well as sickle cell disease. We'll be taking input from the broader community, taking our clinical data package and understanding how we view the value for PYRUKYND in those disease states once we have the pivotal registration trials. That being said, based on what we assume we will get from our clinical studies. For thalassemia, we are expecting in the U.S., we can maintain the price for PYRUKYND in that particular indication. And then for sickle cell disease, we really consider that as optionality. So we have, as you may have heard from us before, 2 primary endpoints in the study, both an improvement in hemoglobin as well as an improvement in annualized rate of VOCs and we think that this is important from a competitive differentiation standpoint, but we'll have to wait and see how the data reads out. So depending on what we see from a data standpoint, we have the opportunity to consider price. Given the size of the patient population, we don't -- we can take a price discount, but still have overall value creation for PYRUKYND across all 3 indications. If we see only one of the endpoints like hemoglobin, seeing an improvement and meeting that endpoint and considering that we could go for a salvage patient population and maintain price across all 3 indications. So more to come once we have the clinical data, and we will continue to study the market and make decisions accordingly.

Another question from Kennen. Is there a companion diagnostic or standardized diagnostic for PKD? How will you approach discovery and diagnosis of the estimated 70% of the PKD population that is not currently diagnosed?

So it'll be the same combination of factors that we've been using today, right? So there is -- we now have ICD-10 code for PK deficiency specifically, which will really help with aiding in the diagnosis. We're continuing to look at claims-based analysis and electronic medical records as well to find patients that might look like PKD patients and could be PKD patients. And then we have genetic testing efforts. So PKD today is either -- it's used both enzyme tests as well as genetic testing, and we'll continue to use those efforts and drive the disease awareness to get more of those patients diagnosed. I think one thing to remember, though, is that prior to today, as Jackie mentioned in her opening remarks, since 1961 when the first PKD patient was identified, there has been no treatment options available. So PYRUKYND is the first one, and that in itself creates a need because you now have a treatment option for these patients to help diagnose even more patients with pyruvate kinase deficiency that were otherwise undiagnosed.

And Kennen you specifically also asked about a companion diagnostic, which there's not a requirement for that with this label. So -- and as Richa said, we are going to continue to work with health care providers on resources to support diagnosing this disease in a faster, better way over time. So...

How many PKD patients have been identified through anemia ID in the U.S. as of today? And how quickly can you get them on PYRUKYND?

So as we had -- I think we mentioned in our Q3 earnings call, we just saw -- we saw a huge uptick in anemia ID at that time. So it's still a little early to really tell you exactly how many patients are coming out of anemia ID. I think one thing to just remember, anemia ID is to help you diagnose your rare hemolytic anemia patients of unknown etiology. So it's much broader than just diagnosing PK deficiency. The value it brings is the fact that it is a very broad panel that can help you diagnose your rare hemolytic anemia of unknown etiology. So more to come on that. I think if -- the couple of considerations here is, one, we are not converting our clinical trial patients, and there is a degree of severity and symptoms that these patients present with. So they see their physicians in a very different dynamic than maybe some other diseases. So depending on that, we can see some pretty variable times when the patient shows up at the physician's office, gets their test and then they'll get prescribed PYRUKYND. So the lead times can be longer.

Great. One more from Mike King. Thoughts on timing of obtaining a J code?

So we have an ICD-10 code. We don't -- I mean, because we are an oral, we won't need a J code for our drug.

Great. Any last questions? I'm not seeing anything else in the chat. All right.

So I'm just going to jump in and say we're super excited about where we are today. First, the genetically defined disease approval as our newly focused genetically defined disease Agios, and the team is extremely enthusiastic to get out there and chomping at the bit, ready to go. And we're as optimistic as ever and believe as strongly as ever in the peak revenue potential for PYRUKYND in PKD with everything that we've seen to date and are very happy with the label that we got that we think is going to get us off to a great start there and really help these patients over a long, long, long time as they're living with this disease. So thank you very much patients for being with us on this journey today, and thanks to everybody else who joined us early this morning. And thank you, Agios' team. Go team.

Thank you, guys.