Alnylam Pharmaceuticals, Inc. (ALNY) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by. Welcome to Alnylam Pharmaceuticals Conference call to discuss our approval of OXLUMO. [Operator Instructions] Please be advised that this call is being taped at the company's request. I'd now like to turn the call over to the company. Please go ahead.

Good morning. I'm Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications at Alnylam. With me today are John Maraganore, our Chief Executive Officer; Akshay Vaishnaw, our President of R&D; and Andy Orth, our Senior Vice President, Head of U.S. Business. Also joining us and available for Q&A are Yvonne Greenstreet, our President and Chief Operating Officer; and Pritesh Gandhi, General Manager of the Lumasiran program. For those of you participating via conference call, the slides that is made available via webcast can also be accessed by going to the Investor page of our website, www.alnylam.com. Now turning to our call, as outlined in Slide 2, John will provide some introductory remarks and offer context around approval of OXLUMO, the trade name for lumasiran; Akshay will review the label and the data that supported the approval of OXLUMO, and Andy will discuss our commercial plans for OXLUMO before opening the call for your questions. Before we begin, I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those in our most recent annual report, quarterly report and 8-K current reports on file with the SEC. In addition, any forward-looking statements represent our views only of the date of this reporting and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I will now turn the call over to John. John?

Thanks, Christine, and thanks to all of you for joining the call today. Last night, the FDA-approved OXLUMO for the treatment of primary hyperoxaluria type 1, or PH1, to lower urinary oxalate levels in pediatric and adult patients. This is a tremendous milestone for patients, families and the community affected by this life-threatening condition for which there were previously no approved therapeutic options. On this holiday week, the FDA approval for OXLUMO is such a wonderful gift for Thanksgiving for the PH1 community. Until now, the only intervention that could alleviate the profound oxalate burden in these patients was a dual liver/kidney transplant. OXLUMO has now become the first ever targeted treatment approved by both the FDA and the EMA to reduce oxalate overproduction and address the underlying pathophysiology of PH1 in patients of all ages. In addition, OXLUMO is now the first ever RNAi medicine approved for use in both adult and pediatric patients, including infants, a significant platform milestone that we believe further underscores the broad potential of Alnylam's RNAi medicines. For Alnylam, OXLUMO is our third commercial product to receive regulatory approval in just over 2 years. With this approval, we have now achieved our Alnylam 2020 goal that we set in early 2015, where we committed to having 3 approved medicines by the end of 2020. With another approval expected by year-end for inclisiran, our investigational RNAi therapeutic in development for the treatment of hypercholesterolemia in partnership with Novartis, we are well on track to actually exceed our original Alnylam 2020 goals. Of course, as you know, regulatory approval is just the first step in making OXLUMO available to patients. As Andy Orth will elaborate further, we are in the midst of proactive discussions with payers in the U.S. to help ensure that patients who may benefit from OXLUMO will have access to it. This approach continues to leverage our innovative value-based agreements, or VBAs, and is consistent with our patient access philosophy and the access track record we've achieved for our 2 previously launched commercial products, ONPATTRO and GIVLAARI. With regard to our global launch plans, we will leverage much of the commercial infrastructure that's already been built for ONPATTRO and GIVLAARI. With the European Commission granted marketing authorization for OXLUMO just days ago, we look forward to making OXLUMO available to patients in Europe as well and are also working on plans to bring on OXLUMO to patients in other parts of the world, including a recent filing for OXLUMO in Brazil. Now there's a lot more coming from Alnylam. By the end of the year, we expect regulatory decisions in the U.S. and Europe for inclisiran to be commercialized by Novartis. Then in early '21, we expect a top line readout from the HELIOS-A Phase III study of vutrisiran in hereditary ATTR amyloidosis in patients with polyneuropathy. This is a critical step in expanding Alnylam's TTR franchise. We're also excited to provide you with an update on our broader pipeline during our virtual R&D Day event next month. In closing, I'd like to take a moment here to express our sincere gratitude to [ patients impacted ] by PH1, caregivers and families, clinical investigators and study staff who have participated and continue to participate in the ILLUMINATE clinical trials. I'd also like to acknowledge the broader PH1 community, notably the Oxalosis and Hyperoxaluria Foundation, the OHF, and research consortia who work tirelessly on behalf of patients. Our ILLUMINATE program would not have been possible without all of you. Additionally, I'd like to acknowledge the FDA for recognizing the immense need for treatments in PH1 and for the agency's urgency in expediting the review of this file during an unprecedented public health crisis, no less, just ahead of our PDUFA date in order to bring OXLUMO to patients as rapidly as possible. Finally, I'd like to also recognize my Alnylam colleagues past and present, whose passion, dedication and unwavering commitment, especially during a pandemic, no less, have made this medicine a reality for patients. So with that, I'll turn the call over to Akshay to review the label and the data that supported it. Akshay?

Thanks, John, and hello, everyone. I certainly echo John's sentiments regarding the sense of pride and gratitude amongst all of us here at Alnylam for having the privilege to be able to bring this innovative therapy to patients, including young children suffering from PH1 as well as their families and health care teams. And to be able to bring our third medicine to market in just over 2 years is especially gratifying. Now to remind you, PH1 is an ultra-rare autosomal recessive disease caused by genetic defect in the liver enzyme, alanine-glyoxylate aminotransferase or AGT, which results in hepatic overproduction of an insoluble metabolite termed oxalate. Whilst the initial onset of disease is typically in childhood, including infancy, patients can present with symptoms at any stage in life and there's significant variability in clinical manifestations and rate of disease progression even amongst siblings. PH1 poses a tremendous physical, emotional and economic burden on patients and families impacted by the disease. We heard this loud and clear at the FDA patient voice meeting in early October. For most, PH1 is an inexorably progressive disease with patients often suffering from extreme pain due to recurrent episodes of kidney stones and grappling with the prospect of the inevitable deterioration of their kidney function. The unpredictable rate of disease progression adds to the angst of not knowing when the next acute stone event will occur or when it may be time to go on dialysis or have to go on a transplant waiting list. With regard to symptoms, whilst kidney stones are the most frequent, first symptom of PH1 and recur throughout life, most patients also experience deposition of calcium oxalate in the renal parenchyma referred to as nephrocalcinosis or calcification of the kidney. This results in progressive and irreparable damage to the kidneys and an accompanying decline in renal function, ultimately leading to end-stage renal disease or ESKD. However, the rate to ESKD, as I mentioned, can be entirely unpredictable and, unfortunately, a significant proportion of patients present with kidney failure. Once kidney function has been fully compromised, dialysis is the only means to remove the excess oxalate from the body. But even with an intensive regimen of several hours a day and upwards of 6 sessions a week, dialysis is inadequate in removing all of the oxalate that the liver continues to produce. This leads to systemic oxalosis with oxalate depositing and accumulating in extra-renal tissues, including the eyes, heart, bones, joints, resulting in vision impairment, cardiomyopathy and pathological bone fractures and, in some cases, even death. Those patients with advanced disease generally require a dual or sequential liver/kidney transplant to resolve the metabolic defect in the liver and to replace [ totally ] damaged kidneys. Complications of ESKD and transplantation are associated with high morbidity and mortality with transplant recipients having to live with lifelong immunosuppression and monitoring and the possibility of needing new organs in the future. Until today, mainstay management options in patients with intact kidney function included hyperhydration with patients including young children having to consume 3 to 4 liters of water per day, crystallization inhibitors and, for a select population of patients with a specific genotype, pyridoxine otherwise known as vitamin B6. Unfortunately, these strategies largely aim to reduce the risk of stones and are generally inadequate at curtailing oxalate overproduction. Let's now turn to the pivotal ILLUMINATE-A Phase III study that formed the basis of yesterday's FDA approval. ILLUMINATE-A was a global randomized 2:1 drug to placebo, double-blind, placebo-controlled trial evaluating the safety and efficacy of OXLUMO in adults and children with PH1. It is the largest interventional study addressing PH1 to date, enrolling 39 patients across 16 sites in 8 countries around the world. To be included, patients had to be at least 6 years of age and have relatively preserved renal function with an estimated glomerular filtration rate, or GFR, of greater than or equal to 30 mils per minute corrected for body surface area. The primary endpoint for the study was the percent change from baseline in 24-hour urinary oxalate excretion averaged across month 3 to 6 treated with OXLUMO as compared to placebo. In the ILLUMINATE-A, treatment with OXLUMO resulted in 53% mean reduction in urinary oxalate levels relative to placebo. In addition, all tested secondary endpoints achieved statistically significant positive results, including 52% of PH1 patients achieving urinary oxalate levels at or below the upper limit of normal at 84%, reaching at or below the upper -- 1.5x the upper limit of normal compared with no patients achieving this endpoint in the placebo group. With regard to safety in the ILLUMINATE-A study, there were no serious or severe adverse events. And the most common adverse event related to OXLUMO was injection site reaction, or ISRs, reported in 38% of patients. ISRs occurred at various time points during the study period, including erythema, pain, pruritus and swelling. The ISR-related symptoms were generally mild and resolved within 1 day of injection and did not lead to discontinuation of the treatment. The agency also took into consideration results from the ILLUMINATE-B pediatric study. ILLUMINATE-B was an open-label single-arm trial, evaluating the safety and efficacy of OXLUMO in PH1 patients under the age of 6, including infants with preserved renal function with GFR above 45. In the ILLUMINATE-B primary analysis, OXLUMO demonstrates a 72% mean reduction in spot urinary oxalate to creatinine ratio from baseline to month 6 averaged from month 3 to 6, at the primary endpoint of the study which -- that was the primary endpoint of the study. In terms of safety, there were no serious or severe adverse events related to the study drug. And the overall safety and tolerability profile of OXLUMO was consistent with that observed in the ILLUMINATE-A pivotal study. Let's move on to the OXLUMO label and review some of the prescribing information. OXLUMO has been approved for the treatment of primary hyperoxaluria type 1 to lower urine oxalate levels in pediatric and adult patients. We're pleased that OXLUMO has been approved without an age restriction, representing a broad initial label. The drug is administered by a health care professional via subcutaneous injection once-monthly for 3 months and thereafter as a convenient once-quarterly dose regimen. The dose is dependent on body weight. And for patients who weigh less than 10 kilograms, dosing remains monthly until they reach a weight of 10 kilograms. I also want to briefly mention that the safety and efficacy of OXLUMO continue to be evaluated in the ongoing ILLUMINATE-C Phase III clinical trial in PH1 patients of all ages with more severe renal impairment, including patients on dialysis. Together, the ILLUMINATE studies comprise a comprehensive clinical development program intended to demonstrate the safety and efficacy of OXLUMO across the full spectrum of patients diagnosed with PH1. We remain on track to report results from the ILLUMINATE-C study in 2021 and, assuming positive results, plan to file a supplemental NDA, including those findings to help inform treating physicians. With that, I will now turn the call over to Andy. Andy?

Thank you, Akshay, and hello, everyone. I'm thrilled to be here to discuss Alnylam's third product launch in just over 2 years, OXLUMO. We intend to leverage the learnings and infrastructure we've built for the commercial launches of ONPATTRO and GIVLAARI to help us successfully commercialize OXLUMO. We believe OXLUMO has the potential to be a very meaningful treatment option for patients with PH1. Let's begin with the overall market opportunity in terms of estimated prevalence of PH1 and the addressable population. Given the heterogeneity in the clinical presentation of this disease, ranging from asymptomatic patients to those who present with systemic oxalosis and ESKD and the significant delays in diagnosis, getting to an exact patient number is a challenge as with any ultra-rare disease. Nevertheless, we estimate the total genetic prevalence of PH1 to be in the range of 4 individuals per million in the U.S. and Europe, with up to 2,100 patients who may have a confirmed PH1 diagnosis. We believe a segment of that population, constituting approximately 1,000 to 1,700 patients in the U.S. and EU, would include patients who are diagnosed but not transplanted and are thus eligible to receive OXLUMO. We expect the initial commercial uptake to be primarily among diagnosed pediatric patients, where there is more urgency to treat and expect robust penetration in the remaining untransplanted patients with active and diagnosed disease over time. In addition, we see further growth opportunity with improved disease awareness and increases in diagnosis rates and as we expand the commercialization of OXLUMO to territories beyond the United States and Europe. We believe this is a commercially attractive ultrarare orphan disease opportunity with over $500 million in global peak revenue potential that we expect to be achieved with steady and continued growth over time. Now let's discuss pricing. Consistent with Alnylam's patient access philosophy, we price our therapies based on the value delivered to patients and the ability to continuously innovate for the benefit of patients. Our overarching access philosophy is grounded in helping patients, delivering value and being proactive. It includes a commitment to refrain from increasing the price of our medicines by more than the Annual Consumer Price Index for urban consumers, on measure of inflation, unless there is new innovation delivering value to patients. It also includes a commitment to proactive engagement with payers to identify innovative approaches for access, such as value-based agreements, or VBAs. We're very proud that across our 2 currently marketed products, we've now executed approximately 30 VBAs. We aim to demonstrate the value of our medicines objectively and transparently and to be a market leader in this regard. Let's now turn to the specifics of OXLUMO. In the U.S., the average price for OXLUMO, before mandatory discounts to government programs, is estimated to be about $490,000 per patient per year. This is based on patient need demonstrated in the ILLUMINATE-A and ILLUMINATE-B clinical trials. In a real-world setting, since OXLUMO was indicated for both pediatric and adult patients, actual costs will vary relative to patient use and weight. We believe the average effective net price for OXLUMO will be about $380,000 when taking into account expected discounts to government insurers and programs such as Medicaid. Patient affordability is a key focus for us. Similar to the patient experience with ONPATTRO and GIVLAARI, we expect commercially insured patients in the U.S. will pay little to nothing in how to pocket costs for OXLUMO if they enroll in our co-pay assistance program. Exact costs may vary based upon patients' individual insurance coverage. We will also offer support for uninsured patients who may be eligible to receive OXLUMO at no charge if they meet certain eligibility criteria. In addition, we've been working closely with the payer community on VBAs that include a new component called a patient need adjustment, or PNA, to ensure seamless access to therapy for patients and budget predictability for payers. Since OXLUMO is indicated for both pediatric and adult patients and is dosed according to body weight, individual need for patients taking OXLUMO will vary and may change over time. To address uncertainty with regard to cost predictability, a participating payer will qualify for a PNA rebate if the average number of vials utilized by a plan member exceeds an established threshold. To further address budget predictability for payers, Alnylam is also making available for OXLUMO its prevalence-based adjustment, or PBA component, which was first introduced last year for Alnylam's second approved therapy, GIVLAARI. There are often uncertainties in diagnosis rates and disease prevalence estimates in ultra-rare, poorly diagnosed orphan diseases, making it challenging for payers to predict the number of patients who will be covered within their plans. This PBA feature triggers a rebate to participating payers if the number of diagnosed patients they cover exceeds current epidemiological estimates for PH1. When determining the price of OXLUMO, we prioritize patient access and delivering value to payers and physicians. 5 factors also influence OXLUMO's price, including the following: First, we consider the debilitating and life-threatening nature of this inherited disease. Second, we consider the high burden of the current standard of care, which involves intensive management of kidney stone episodes with patients often having to endure extreme pain, undergo hospitalization and surgical intervention and, once the disease progresses, a ruling dialysis regimen. The third factor we considered is the ultra-rare nature of this condition with an estimated 1,000 to 1,700 patients in the U.S. and Europe who may be diagnosed and have not yet received a transplant. Additionally, OXLUMO is the first approved therapy to treat PH1 by substantially reducing urinary oxalate, a toxic metabolite responsible for the severe clinical manifestations of this disease. And finally, our enhanced VBA framework that incorporates innovations such as PNAs and PBAs that support access and give participating payers greater short-term and long-term budget predictability, thus reducing insurance barriers for adults and children with PH1 who are prescribed OXLUMO. Regarding timing for availability of OXLUMO, FDA approval came just ahead of our PDUFA date of December 3. Nevertheless, we expect to have OXLUMO available for shipment to health care providers in the U.S. by the end of the year. And beginning right now, health care providers can initiate the process for getting a patient on OXLUMO therapy by completing and submitting a start form through Alnylam Assist, our U.S. patient services program, which I'll touch on shortly. All key elements to support OXLUMO launch are in place. We have pivoted to digital-first in the current environment, and our OXLUMO educational and planned promotional efforts have been optimized for both use -- for use in both digital and in-person engagements. We have launched a number of educational websites specifically tailored to our patients, caregiver and HCP audiences. We're especially proud of our award-winning PH1 Of A Kind children's video animation series, a terrific educational resource that we co-developed with the Oxalosis and Hyperoxaluria Foundation for pediatric patients and their caregivers. Our core field-based roles are trained, in place and ready for launch. We will interact with our customers and the PH1 community using multiple engagement models and are having success educating on PH1 to further raise disease awareness and improve diagnosis. We've also been collaborating with patient advocacy groups, such as the OHF as well as other patient groups focusing on kidney health, who have very important capabilities and intimate knowledge of the needs of the patient community, and we plan to continue these collaborative efforts. Additionally, we continue to offer Alnylam Act, a third-party genetic testing initiative, sponsored by Alnylam, aimed at facilitating diagnosis to patients suspected of having PH1. We are also extending our in-house patient services capability, Alnylam Assist, to cover OXLUMO. Alnylam Assist is a comprehensive patient services program that offers support to patients throughout treatment and has consistently earned excellent patient satisfaction rankings for our ONPATTRO and GIVLAARI patients. The final piece is our continued proactive engagement with payers, as I mentioned earlier. We recognize that our efforts in advancing OXLUMO to market will only be successful if patients who may benefit from this new medicine have access to it. In closing, I'd also like to thank the patients, caregivers, patient advocates and study investigators and staff that continue to work extraordinarily hard for the PH1 community. I'll now turn the call back to Christine to coordinate Q&A. Christine?

Thanks, Andy. Operator, we will now open the call for questions. [Operator Instructions]

[Operator Instructions] We will take our first question from David Lebowitz from Morgan Stanley.

Congratulations on the approval. When you look forward to the launch, what is the typical diagnosis age of patients at this point in time? And what would you say is the ideal diagnosis age given the nature of lumasiran? And how do you, I guess, intend to push the diagnosis age down going forward?

Yes. First of all, thank you, David, and that's a great question. Obviously, and I'm going to hand it over to Andy. But obviously, as it is important for health that patients get treated as soon as possible. We know that as oxalate deposits in the kidney, as kidney stones are formed, there's damage. Some of it can be irreversible, that ultimately needs to be reckoned with. And so getting to patients as quickly as possible is a major priority from the standpoint of optimal therapy. Andy, do you want to answer David's questions?

Yes, sure. Thanks for the question, David. In the beginning here as we launch, the most obvious are going to be the young patients, David, who shouldn't be forming stones in any way, shape or form. They tend to be the easiest "to diagnose" as they get sent to centers or to specialists. As we continue to increase disease awareness across nephrologists, both adult and pediatrics, and urologists, we're going to see that age actually increase to folks who are forming these stones a little later in their life. So hopefully, that answers your question?

Moving on to our next question, comes from Maury Raycroft from Jefferies.

Congrats on the update. Question is just how many patients from your current clinical trials do you expect to convert to commercial drug? And can you talk about timing expectations around this?

Yes. Great. Thanks, Maury. I'll start -- I'll turn it over to Akshay in a second, but just remind you, Maury, that patients in the clinical studies go on to an open-label extension study for a period of time, and that's an important way to collect safety data. Akshay, do you want to talk about the specifics of when patients come off the open-label study?

Yes. So as with any rare disease, there's an expectation to continue patients onto label extension studies because, clearly, the number of patients studied is not as large as in prevalent diseases. So they'll continue for a number of years, and we'll accumulate safety information, which will be important for the further understanding of the drug. I've forgotten the precise number of years. Pritesh may -- you might want to drop in on that.

Yes. Thanks, Akshay, and thanks for the question, Maury. So as both Akshay and John had mentioned, we do have open-label extension studies. Outpatients do get followed up in our open-label extension studies for a period of 5 years. So once the patients have received clinical supply in the clinical trial of the open-label extension study for 5 years, that is when they will convert to commercial supply.

We'll now take it from Alethia Young from Cantor Fitzgerald.

Hello, Alethia?

Can you hear me? Can you hear me?

Now we can. Yes, you might have been on mute. Yes.

Congrats on your third one, and there's many more to come, but I wanted to ask about where -- if there's any kind of like potential founder effect or what might be your best markets around the world and kind of pockets for this PH1?

Yes. Thanks, Alethia. Akshay, do you want to handle that?

Yes. So Alethia, in contrast to some other genetic diseases, there is no enormous founder effect in the sense of a particular mutation being concentrated in a geographic area or country. One thing that does occur, and this is seen with other autosomal recessive disorders, is there tends to be a slightly higher incidence in areas where there's consanguinity. And so those parts of the world where there may be higher rates of consanguinity are associated with higher rates of this disease. But generally speaking, the mutations that result in this disease have been seen all in the world.

We'll now take it from Joel Beatty from Citi.

Congrats on the approval. Could you characterize the number of patients in the expanded access program? And any -- other patients that may be waiting to get on the drug in the near term?

Yes. Thanks, Joel, and thanks for your congrats at the beginning. I appreciate that. Well, we don't give out specifics on that for reasons, including competitive reasons. But we do have a very active global expanded access program in countries where we can make OXLUMO available for physicians to provide it to their patients. We don't give the numbers, but it's a double digit -- significant double-digit number around the world. And we look forward to converting patients on to active drug when P&R occurs. I mean, obviously, in some European countries, they won't be able to get out to commercial drug for 12 to 18 months until we get pricing and reimbursement. So -- but that does represent a pool of patients that will be available in the future for commercial drug on top of patients that will come out to commercial product without having gone through the expanded access program. I don't know, Akshay, anything to add on that from your perspective?

No. No, you covered it, John.

We'll now take it from Gena Wang from Barclays.

I also wanted to add my congrats as well on the early approval and the broad label.

Thank you.

Sure. So the question is for the value-based adjustment of patient need adjustment, just wondering if the threshold is a for patient per million? And is that the same across different programs? And similar for patient need adjustment, not sure if you can share what the numbers of the threshold or the values. But if not, can you give a little bit of direction on at which stage if we're using adult patient that will trigger that threshold? And then lastly, quickly on the WAC price and the net price, is that the maintenance price beyond the initial loading dose?

Yes. Thanks for that, Gena, and thanks for your congratulatory note. Before I hand it over to Andy, let me just say that, obviously, the value-based agreement framework that we've engineered for OXLUMO is something we're very proud of. We've been able to develop this in consultation with some members of the payer community. And we think it really helps address budget certainty for the payer community. And I expect it to be very well received by the payer community. And when we do these value-based agreements, of course, we also put them in place with certain commitments from the payers, in turn, to reimburse the product for the label to not put in place any step edits and so forth. So it really is a give-and-take arrangement that has been very successful in our other 2 brands. So with that as context, Andy, do you want to answer her specific questions?

Sure, sure. So with the VBAs, Gena, we engage in a dialogue with the payer, and it's highly data-driven. Some of the data is clearly ours, right, from the clinical trial nature, how much product are the individual patients consuming at various sizes and at various times, et cetera, as well as epidemiological data we find out in the academic research. So we bring that to the table and then go back and forth with the payer. So there are differing numbers between different diseases clearly on that front. And each one is a bit bespoke, but we don't release the specific numbers. And then for the question you also ended with, the prices we did cite are indeed maintenance dosing, right, are ongoing at that point in time. And was there one more question you had in the middle, Gena? I can't remember.

The vials, the threshold of vials.

The threshold, yes. And that's something we're not releasing at this point in time. Yes.

We'll now take our next question from Ritu Baral from Cowen.

I wanted to ask about the patients that are sort of left on the table with the current label. You mentioned the non-transplanted patients are about 1,000 to 1,700 per slide 14. But how should we think about those patients with impaired renal function that have not yet been transplanted and would be covered by the ILLUMINATE-C SMBA? And then just comparatively, very quickly, can you talk about how important patient identification and Alnylam Act and Assist are in -- for OXLUMO versus ONPATTRO and GIVLAARI?

Okay. That's a great question. Why don't we have the first question answered by Pritesh? And then Andy, you can answer the second question. Go ahead, Pritesh.

Thanks, John, and thanks, Ritu, for the question. In terms of the non-transplanted patients, right? So we're talking really about the patients here that are diagnosed in terms of the numbers that Andy provided, right? We also understand that about 50% of the patients are not diagnosed currently. And we will be working, of course, with clinicians and engaging clinicians in disease awareness efforts including the Alnylam Act to try and discover patients, identify patients so that we can accelerate the time to diagnosis. In terms of the impaired renal function, I mean, as we have seen in the label, we are currently -- we don't have data right now in patients with an estimated glomerular filtration rate less than 30 mils per minute, including dialysis patients. And those patients are being studied in the ILLUMINATE-C study, and we will see those data in 2021 and then we'll make a decision.

And then, Andy, do you want to answer the second question on patient finding? And how will it look versus ONPATTRO and GIVLAARI?

Sure, sure. Thanks, Ritu, for the question. So clearly, patient finding here is going to be critical, and it's something we've begun very skilled at through the launches of ONPATTRO and GIVLAARI. And we'll use all the same tools, techniques and technologies, we've had such great success with in both of those. On Alnylam Act specifically, clearly a little bit different here with the autosomal recessive population. But we are having success using this as a confirmatory tool out there when we do identify these patients with their health care providers.

Got it. So no good idea right now on that ILLUMINATE-C population yet? We'll understand more later.

Exactly. Yes, I think that's the [ protectionist ] answer. I think that's the safe thing to say right now.

We'll now take our next one from Anupam Rama from JPMorgan.

This is Tessa on the call this morning for Anupam. Congratulations from us as well on the approval. So just one from us. You also recently got approval for OXLUMO in Europe. What are some of the similarities and differences worth noting between the U.S. and EU in terms of market dynamics in PH1?

Yes. Thanks. And Tessa, we appreciate the congratulatory comments. Pritesh, do you want to talk a little bit about the U.S. versus Europe dynamics a little bit?

Yes. Sure. Thanks for the question. Really appreciate it. And thanks for your congratulations note as well. It's very different in the U.S. versus the EU as we had expected, right? I mean, in the EU, specifically in countries like France, there are already centers of excellence that are existing. And the patients do go to those centers of excellence and the diagnosis happens in those centers of excellence. In the U.S., in contrast, there are relatively few centers of excellence, and that is a little bit fragmented as expected. And we do anticipate that there will be patients in the centers of excellence in the U.S., but also that we will be able to find patients in the community as we have seen with our other rare diseases as well. So we -- with our disease state efforts -- disease awareness efforts, we will be able to find additional patients in the community [ and using us ].

Andy, anything else from your perspective on this question?

No. Just similar to -- you already mentioned it, John, right, the U.S. will be out in front with immediate reimbursement and patient finding and developing the market there. And then the reimbursement trends we're going to see throughout Europe and P&R will be much more similar to GIVLAARI.

Great. Tessa, does that answer your question?