Ladies and gentlemen, thank you for standing by and welcome to the Alnylam Pharmaceuticals Conference Call to discuss Fourth Quarter and Full Year 2020 Financial Results. There will be a question-and-answer session to follow. Please be advised that this call is being taped at the company’s request. .

Good morning. I'm Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications at Alnylam.

With me today on the phone are John Maraganore, Chief Executive Officer; Tolga Tanguler, Chief Commercial Officer; Akshay Vaishnaw, President of R&D; Jeff Poulton, Chief Financial Officer; and Yvonne Greenstreet, President and Chief Operating Officer. In addition, Andy Orth, Senior Vice President and Head of the U.S.

Business, is on the line and available for Q&A. For those of you participating via conference call, the accompanying slides can be accessed by going to the Events section of the Investors page of our website investors.alnylam.com/events.

During today's call, as outlined on slide two, John will provide some introductory remarks and provide some general context. Tolga will provide an update on our global commercial progress. Akshay will review recent clinical and preclinical updates.

Jeff will review our financials and Yvonne will provide a brief summary of upcoming milestones, before opening the call to your questions.

I would like to remind you that this call will contain certain 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 discussed in our most recently quarterly reports on file with the SEC.

In addition, any forward-looking statements represent our views only of the date of this recording 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'd like to turn the call over to John.

John?.

Thanks, Christine, and thank you everyone for joining the call today. Despite the challenges we all faced in 2020 with the COVID-19 pandemic, Alnylam had one of its strongest years ever as a successful global commercial organization with a highly productive R&D platform.

We delivered on our commercial expansion, growing top line product revenues by over 100%, driven by strong continued execution for ONPATTRO and GIVLAARI. We continue to advance the pipeline, which includes programs across both rare and common disease populations.

And we remained focused on financial discipline to help us reach our goal of achieving a self-sustainable financial profile..

Thanks, John and good morning everyone. I appreciate the warm welcome, and couldn't be more excited to join the Alnylam team. Let's get started with a review of our commercial performance.

For ONPATTRO, we achieved $90.4 million in global net product revenues in the fourth quarter, representing approximately 10% quarter-on-quarter growth compared with Q3. And we achieved $306.1 million in global ONPATTRO revenues for the full year 2020..

Thanks Tolga and good morning, everyone. I'll start with our efforts in ATTR amyloidosis where we're advancing our two product candidates patisiran and vutrisiran. ONPATTRO is currently approved in multiple markets around the world to treat the polyneuropathy associated hereditary ATTR amyloidosis.

We're committed to expanding the products label for the treatment of cardiomyopathy in both hereditary and wild-type ATTR amyloidosis patients..

Patient demand increased 13% driven by the addition of new patients on therapy, with patient compliance remaining consistent with Q3 when we returned to pre-pandemic levels. Inventory destocking during the quarter compared with modest stocking in Q3 reduced reported growth during the quarter.

We ended the quarter with just over one week of inventory in the channel in the U.S. We're really pleased with the continued strength in our U.S. results, with two consecutive quarters of double-digit growth, following a pandemic challenge Q2 and with Q4 sales representing the highest level since launch.

In our international markets, ONPATTRO performance remained strong with growth of 9% versus Q3 2020, primarily driven by increased patient demand broadly across Europe and Japan. Additionally, there was a modest benefit from inventory stocking in Japan at year-end. Turning to our results for GIVLAARI.

We had a strong fourth quarter, generating $22.1 million in global net revenue, representing 33% growth compared to the third quarter of 2020. Revenue in Europe during 2020, as expected, was primarily generated from two markets, Germany and France.

As we saw with ONPATTRO in year two of its commercialization, as we secure pricing and reimbursement, we anticipate additional markets for GIVLAARI coming online across Europe and Asia in 2021. Turning now to a summary of our full P&L results for the quarter and full year.

Total product sales for 2020 were approximately $362 million, which were more than double 2019 with ONPATTRO delivering more than 80% growth versus 2019 and GIVLAARI contributing $55 million in its initial launch year.

Net revenue from collaborations for the fourth quarter was $50.7 million primarily due to revenue recognized from our Vir and Regeneron collaborations and a $15 million increase around milestone from Novartis following the December EU approval of Leqvio.

Gross margin as a percentage of total revenue was 86% for the quarter, up from 83% in Q4 2019, primarily due to ONPATTRO inventory write-off that occurred in Q4, 2019.

Our non-GAAP R&D expenses in the fourth quarter 2020 decreased compared to the same period in 2019, primarily due to Q4 2019 having a high level of expense associated with clinical material manufactured for future clinical trials.

Our non-GAAP SG&A expenses increased in the fourth quarter of 2020 compared to the same period in 2019, primarily due to increased investment in commercial and medical affairs activities to support the ongoing launches of ONPATTRO and GIVLAARI and the launch preparation activity for OXLUMO.

Our combined non-GAAP R&D and SG&A expenses were $1,063 million in 2020, representing 11% growth versus 2019, which was significantly lower than the growth in combined at non-GAAP R&D and SG&A expense in 2019, which was 31%.

As I've noted on several occasions over the last year, this more moderate level of OpEx growth is one of the key levers supporting our path towards profitability.

Our non-GAAP operating loss for the quarter decreased by approximately $82 million compared to the same period in 2019, driven by strong top line growth and flat non-GAAP combined R&D and SG&A expense.

Full year non-GAAP operating loss ended at approximately $649 million, which is $116 million favorable to our full year 2019 non-GAAP operating loss, consistent with our past guidance that 2019 would be our peak loss year.

We ended the year with cash, cash equivalents and marketable securities of approximately $1.9 billion, up from $1.5 billion at the end of 2019.

Cash was favorably impacted in 2020 by the $2 billion Blackstone strategic financing collaboration that we announced in Q2, which contributed approximately $800 million in financing this year, including $200 million in Q4 related to the initial drawdown of the debt facility with GSO Blackstone's credit arm.

Now turning to our financial guidance for 2021. Starting with net product revenues, we are now transitioning to providing combined net product revenue guidance from ONPATTRO GIVLAARI, and OXLUMO.

We anticipate combined net product revenues for these three products will be between $610 million and $660 million with the midpoint representing more than 75% growth compared to 2020. Vutrisiran approval is not expected until early 2022, so it was not factored into our guidance for product revenues this year.

It is also worth noting that our guidance reflects the uncertainty related to the COVID-19 pandemic, which should decrease over time as the vaccine rollout progresses around the world.

Our guidance for net revenue from collaborations and royalties is a range between $150 million and $200 million with the midpoint of the range representing more than 30% growth from 2020. Growth in 2021 is expected to come primarily from our collaboration with Regeneron and royalties and milestones from Leqvio.

Our guidance for combined non-GAAP R&D and SG&A expense is a range between $1,175 million and $1,275 million. The midpoint of the guidance range represents a projected 15% increase compared with 2020.

We anticipate SG&A growth will be modest as we generate operating leverage from our existing commercial infrastructure to support our three commercial products.

We expect a higher rate of growth for R&D driven by investments in our two Phase 3 ATTR cardiomyopathy studies, APOLLO-B and HELIOS-B, as well as initiation of two robust Phase 2 studies in our AGT program for hypertension.

Finally, achievement of the top line and non-GAAP operating expense guidance we have provided today, 2021 will deliver another year of improvement in our non-GAAP operating loss, as we continue to make progress on our path to delivering sustainable profitability. With that, I'll now turn the call over to Yvonne to review our goals for 2021.

Yvonne?.

Thanks, Jeff and hello everyone. 2021 is shaping up to be a productive year for Alnylam, as we embark on a new five-year chapter of our journey outlines that Alnylam P5x25 guidance. This past year, we plan to continue our global commercialization of ONPATTRO, GIVLAARI and OXLUMO.

We look forward to major market approvals in Japan for GIVLAARI and Brazil for OXLUMO. We plan to continue advancing our ATTR franchise program with the ongoing ATTR cardiomyopathy study. For patisiran, we expect to complete enrollment in the APOLLO-B study early this year. For vutrisiran, enrollment is ongoing in the HELIOS-B study.

In following the HELIOS-A positive top line results, we look forward to filing an NDA and presenting nine months results at AAN in April. In 2021, we also plan to report additional data on the 18-month endpoint, which include a larger number of exploratory cardiac endpoints measures.

We expect to start studying our biannual dose regimen of vutrisiran in early 2021. For Lumasiran, the ILLUMINATE-C Phase 3 study is expected to have top-line results midyear and we look forward to initiating the KARDIA 1 and 2 Phase 2 studies for ALN-AGT in hypertension. And, of course, we're excited about what's our partners have in store this year.

Novartis will be executing on the initial launch of Leqvio and aiming for U.S. approval. And Sanofi will be advancing for fitusiran in the ATLAS Phase 3 program. Finally, you can expect additional data readouts from our pipeline during the course of the year.

2021 marks the starts the next chapter for Alnylam, with sights set on our new five-year goals become one of the most successful companies in the industry. We're eager to deliver on this ambition and look forward to updating you throughout the year. Let me now turn it back to Christine to coordinate our Q&A session.

Christine?.

Thank you, Yvonne. Operator, we will now open the call for your questions. To those dialed in, we'd like to ask you to limit yourself to one question each and then get back in the queue if you have any additional questions..

Our first question comes from the line of David Lebowitz from Morgan Stanley. Your line is now open. .

Thank you for taking my question. When you look at GIVLAARI performance thus far, it seems to be doing quite well.

Has this caused you to, number one, reevaluate what the size of the market is for GIVLAARI in general? And has it changed the way you look at markets for these types of diseases and what you think of what the ultimate opportunity for these types for PH1 porphyria and other diseases its nature might be..

Thank you, David. I think that was you David. I think that's a good question. Obviously, GIVLAARI was really off to a good start and had a very strong year, its first full year of launch last year and we look forward to its launch into -- continued launch in 2021.

And we do expect continued growth in 2021, driven not only by new patient finding, but significant geographic expansion that will be occurring by virtue of PNR. And also, approvals we expect in major markets like Japan in 2021. Let me turn it over to Tolga and Andy Orth maybe to comment further.

Let's start with Tolga, anything to add to that?.

Thanks, John. And hi, David. Good morning. No, John essentially -- I mean, it's good to be recognized with a good strong performance of GIVLAARI, especially during a pandemic era that says a lot about the capabilities of the organization and how we've been able to launch this both in the U.S. and ex-U.S.

And to your point, we do anticipate an approval in Japan. So, overall, I think the trends are good. It's also a good sign of the value of the medicine that provides to these patients that have not been properly treated..

Andy, anything to add to that?.

Yeah. I would just add that. We continue to be really excited about the opportunity. We still think this is a half billion dollar opportunity for the company globally. And the learnings we're gaining here, as we go through 2020, will hopefully allow us to accelerate that as we get into 2021 and 2022..

Right. Thank you.

David, does that answer your question?.

Thank you. Thanks for taking my question..

Great..

Thank you. Our next question comes from the line of Joel Beatty from Citi. Your line is now open..

Hi. Thanks for taking the question. I'm curious, could you share any insight into the ability to have combination therapy in TTR with any competing drugs in the U.S. and how that compares with ex-U.S.

markets?.

Yeah. That's a great question. A very important one and one that defines an important part of the dynamics of the ONPATTRO execution and market dynamics in the U.S. and rest of world.

So, why don't we go to Tolga to add some more color on that question?.

Yeah. Would you be able to repeat the question again? I wasn't quite sure if you were asking about the sort of the concomitant use..

Yeah. Concomitant use of ONPATTRO with competing TTR agent, is that different in the U.S.

versus ex-U.S.?.

Right. No, it is. It is different. What we see in the U.S. in particular is that there's about 20%, 25% of the utilization of current ONPATTRO patients are actually also on tafamidis. We do see that in ex-U.S., we tend to see a much rapid switch from TTR stabilizers to silencers. That's what we've experienced.

However, in some markets, we also see some minor level of concomitant use as well, when it comes to using a stabilizer than a silencer..

And just to emphasize the point, obviously, the use of ONPATTRO is for the treatment of the polyneuropathy that exists in these patients, which is where it's indicated. So, these are hereditary ATTR patients that have polyneuropathy and likely have a mixed phenotype, which is why they may be getting both drugs..

Absolutely. Yes..

Great. Thank you..

Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open..

Good morning. Thanks for taking my question. I'm just curious if we're going to see an interim analysis here on HELIOS-B and when we can expect that and what we should expect to see..

Yeah. Great question, Salveen. So, just as a reminder, and I'm going to hand this over to Akshay in a second. But as a reminder, HELIOS-B is our randomized double blind placebo controlled study of vutrisiran compared to placebo on top of standard-of-care for the treatment of ATTR amyloidosis with cardiomyopathy.

So that includes both hereditary as well as wild-type disease. The study is enrolling quite well. We are going to be enrolling throughout 2021, but we're really pleased with how well the enrollment is going. But your point about interim analysis, let's turn it over to Akshay..

Yeah. Thanks, Salveen. So, I think, we have a wonderful option to do an interim analysis in HELIOS-B. There are a number of approaches we can consider. But importantly, we want to use all data elements to inform that interim analysis. And we have data from the original patisiran APOLLO study itself.

We now have data from HELIOS-A, nine months to 18 in patients with mix the ATTR disease with cardiomyopathy, those were exploratory data on BNP, which we've shared showing improvement in BNP.

And we're going to get 18 months data later in the year that will encompass, not just BNP and echo data, but some technician's scan data and also can be to test another element. So there are a lot of datasets coming, that continue to inform us about the potential for RNAi based approaches for ATTR cardiomyopathy.

And most importantly, next year, as we've just guided, we'll get APOLLO-B data on the six minute walk distance. And so, these are the elements that will go into our thinking. There are lots of options. We're excited about it and we will update you when we have finalized the approach..

Great.

Does that answer your question, Salveen?.

Yes. Thank you..

Excellent. Thank you. Our next question comes from the line of Paul Matteis from Stifel. Your line is now open..

Great. Thank you much for taking my question. I wanted to ask just a broader pipeline one. Last year AGT really came into the forefront.

If you had to pick one of your earlier programs that you featured in R&D Day or in the CNS pipeline that you don't think it's discussed right now, but might be at the forefront of the conversation by the end of this year early next, which would you pick? And then one piece of that, I'm a little surprised you guys don't have anything in neuromuscular, given the amount of funding that's gone into conjugation approaches there.

Are there any -- is that all of interest of you with RNAi? Thanks a lot..

Okay. Great questions, Paul. So, I'm going to give you my view and then we'll go to Akshay and then we'll go to Yvonne. So you get three different perspectives on it. And then, we'll come back and Akshay will address the question on neuromuscular.

Look, from my perspective, a program in our pipeline that, I think, we'll get a lot of attention this year is ALN-APP. That's our RNAi therapeutic targeting amyloid precursor protein. It's our first CNS program. It's really going to be a defining moment for extra hepatic delivery of RNAi therapeutics.

And we're leading the way on the translation of this remarkable technology for the treatment of neurodegenerative diseases, where there's just enormous unmet need. And so, I think that's going to be a landmark program for the field and for Alnylam and for the future of our pipeline. So that's my pick. Let's go to Akshay next..

I was going to pick that. Okay. I'll pick something. I think we have the benefit of many, many interesting targets we're addressing -- to address a high unmet medical need. I trained as a rheumatologist, the SDH program, which we featured at R&D Day will address gout.

Gout is a hugely prevalent global disorder, not only the rheumatologic disorder, but it can impact the kidneys and kidney function. So very, very important disease and one that's rapidly increasing in incidents by the way. So we would love to make a bet that the animal data are very encouraging.

We can get over 95% knocked down at the target SDH, with over 50% reduction in peripheral blood urea levels. It be interesting, based on the Phase 1, which I think will be very informative and we can achieve a lot without Phase 1 to figure out how to position exactly and help the most patients.

But as part of our broadening into common disease, that's another element beyond AGT and the NASH programs like SDH. John's talked about APP and outsiders. So, I'd pick the SDH program.

Yvonne?.

Yvonne?.

Okay. Well, I'm going to pick the HBV program for three reasons. One, HBV is enormous opportunity. It's a disease that afflicts close to 300 million people around the world. So, incredibly important. Second reason is I think the encouraging base that we've had from our Phase 2 study with the one and a half log reduction in HB surface antigen.

And obviously, in partnership with Vir, that's now being studied in combination. And I think has the opportunity to affect functional cure for these patients, which would be absolutely tremendous. And then the third reason is the fact that we have a 50/50 three option and a right price to Phase 34.

So, I think this could start some kind of program that we spend a little bit more time talking about it as the year goes on..

Absolutely. And we're encouraged to -- by the progress that Vir has been making. And I'm sure there'll be quite a bit of new data this year on that program.

So, Akshay, do you want to handle the neuromuscular question?.

Yeah. Paul, so, I mean, I think we are doing a good amount of work actually in neuromuscular disease. If we think about it, that front center, we've got all our work in ATTR amyloidosis, the polyneuropathy there is -- it's a peripheral neuropathy and so it is squarely a neuromuscular disorder. Of course, it's impactful in the hereditary situation.

Increasingly we hear about neuropathy in wild type and I think that'll be an important area to think about as well. ONPATTRO is approved, of course, for the hereditary polyneuropathy in ATTR. So, that's one area.

We're going to do a study of HELIOS-C which we intend to kickoff later in the year with vutrisiran to prevent the onset of this syndrome, hATTR amyloidosis more to come on that. And separately, we've got programs in ALS.

There are a number of genetically validated targets in ALS that people are familiar with sort of one and others and that's under the basket or programs with Regeneron where we collaborate. So that's another neuromuscular disorder caused with Regeneron. We're also pursuing Myasthenia Gravis with the Cemdisiran and C5 anthropoid Pozelimab.

So more details on those. The Regeneron collaborative programs to come I'm sure later in the year, actually. And beyond that, we are doing work in lots of additional neuromuscular disorders at a research and preclinical stage, that we don't necessarily share until the data mature enough to discuss.

But I can assure you, there all programs ongoing in other disorders, including common inherited peripheral neuropathy, for example, we're interested in. So, lots going on in neuromuscular disease. And I think, we're pretty excited about the progress we've made and certainly the dent we've made in hATTR amyloidosis polyneuropathy..

Thanks, Akshay.

Paul, does that answer your question?.

Yeah. Thank you..

All right. Great..

Thank you. Our next question comes from the line of Tazeen Ahmad from Bank of America. Your line is now open..

Hi, guys. Good morning. Thank you for taking my question. Wanted to get your thoughts on, how you think the ATTR market in general is developing? Do you have a better sense of how much of being addressable patients have been diagnosed, and how the stabilizers are helping to develop that market? Thanks..

Well, that's a great question, Tazeen. And let me kick it off by saying that we have a multi-product multiyear perspective on the broader ATTR franchise at Alnylam -- a franchise we're we aim to be the leader across the industry, helping patients with the medicines and the innovation we bring forward.

Obviously, today we are approved with one product for the treatment of the polyneuropathy of hereditary ATTR amyloidosis. ONPATTRO is off to a terrific start. It is the market leading product for treating polyneuropathy with this disease. And we're really pleased with the performance that we've seen.

We expect continued growth in the polyneuropathy segment for ONPATTRO alone. At the same time, we just recently reported positive Phase 3 data with HELIOS-A which will open up the opportunity for vutrisiran once quarterly subcut drug, which with additional work we believe we can make it once every six monthly subcut drug.

And we should expect approval next year in ATTR polyneuropathy, which we believe will expand the polyneuropathy opportunity beyond even ONPATTRO. And then, of course, is as Akshay mentioned a minute ago, we open up the door with the APOLLO-B study mid next year, assuming positive data with cardiomyopathy both wild-type and hereditary.

So this is really a multiyear growth opportunity for the innovation that we're bringing forward for the treatment of this disease.

Tolga, do you want to comment a little bit further? Andy, you as well in terms of how we see this evolving over time?.

No, I think, John, you said it very nicely. We certainly see this category evolving as the time goes by. And as John indicated, obviously, we now have a one indication with ONPATTRO that's becoming -- that is the leader in the silencer market for polyneuropathy. But we know that there are tale of two cities almost.

You have the polyneuropathy, that's more of a rare disease with a lesser prevalence, given the hereditary condition. And then, obviously, there's the wild-type that we certainly don't have the indication yet with cardiomyopathy. But the diagnostics of that is probably going through the same route, which is really an inexpensive PYP scan.

That access -- having that access has significantly increased our ability to be able to diagnose with more polyneuropathy patients. And if, HELIOS-A as well as, -- sorry -- HELIOS-A as well as APOLLO-B, if they were to succeed, we certainly will be able to take advantage of much larger cardiomyopathy segment.

So, from Alnylam perspective, what we're already demonstrating with ONPATTRO and its leadership in polyneuropathy, I think is a great signal for us to be able to actually define how are we going to be able to play in this current segment, as well as be able to provide the right medicine for other segments, if our products were to be approved.

Andy?.

Yeah. And just to add, the hereditary and the wild-type markets are in the very early stages of their growth for what we expect them to be. And that's going to happen over the next one, two, five to 10 years. And as John and Tolga highlighted, our portfolio that we're going to bring to bear here, puts us in an excellent position.

So, we're really pretty excited about it..

And Tazeen, I agree with everything that Tolga and Andy just said.

I have often made the analogy of where the ATTR marketplace will go over time to what happened with multiple sclerosis, and with many products, many mechanisms of action and obviously major patient impact at the end of the day, along with obviously significant revenue and overall value of that market.

So, I think you will see that materializing in a way that will accommodate multiple opportunities for patients at the end of the day. And Alnylam is going to be a major leader in this space..

Okay. Thank you..

Thank you..

Thank you. Our next question comes from the line of Ritu Baral from Cowan. Your line is now open..

Hey, guys. Thanks for taking the question. I'm going to be upfront. It does have a couple of different parts, but it's all on ONPATTRO performance, which continues to be really strong.

One, how much does home infusion present a tailwind to what we've seen over, especially over Q4, and long-term, can you maintain coverage of home infusion? Are you planning on potentially expanding the sales effort with the vutrisiran approval in early 2022? And then lastly, just any color on a policy Akshay, you sort of threw it out there, prevention of symptoms, but anything else you can say about that?.

Okay. So, let's -- why don't we -- Akshay, why don’t you quickly answer the HELIOS-C question and then we'll go -- we'll give Tolga and Andy some time to reflect on the ONPATTRO questions and we'll go to them. So, Akshay..

Sure. Ritu, when we looked at the original APOLLO data is very clear that potent significant reduction of TTR 80% or so. It was associated with remarkable outcomes for polyneuropathy and for the cardiac aspects in those with mixed disease, we think. And the drug was labeled for the treatment of the polyneuropathy of hATTR, which is right and proper.

But as we looked at the detailed data, patients with very early disease with lesser disease burden did very well and all -- their M&A scores went down to single digit, so very close to zero, and that led to the hypothesis that what if you could give the drug even before the overt onset of disease in patients with very low or maybe no evident polyneuropathy and can we prevent the onset of symptomatic disease.

And I think we feel very optimistic about that. Similarly, we now know that patients are being diagnosed or being identified as having TTR deposits in the heart before the onset, despite by technetium scan before the onset of clinical disease. And so, it's a very reasonable hypothesis, and I think one with a highlighted success.

But if we can turn the tap off and substantially reduce TTR levels, that we can substantially reduce the occurrence of this disease and prevent its onset. So, that's what we're working on now. We intend to start the study, which will call HELIOS-C with vutrisiran later in the year, the subcutaneous injectable once every six months or so.

And more detail to follow. But I think it's a very, very exciting hypothesis and how often in a rare disease to be getting a chance to try and help patients by preventing the onset of disease..

Great. And let's go to Tolga first on the commercial questions on ONPATTRO, and then vutrisiran and the sales effort.

Tolga?.

Sure. And thanks, John. A great question, and you're right. We're very pleased with the growth of ONPATTRO quarter-over-quarter. And certainly that will be -- it will be driven by continuous patient finding. And if appropriate, the switch outs from the patient's current treatments.

Now, in regards to patient access, obviously, with the pandemic, what we've seen is a good steady increase of patients being able to access home infusion, particularly in the United States and Europe.

Those rates have gone up, but we also believe that patients have been actually able to -- as well as the healthcare systems been able to quickly pivot and provide alternative care sites for patients, as well as providing easy access to infusion clinics.

So, we're pleased that we have the ability to be able to either redirect those patients to alternatives site cares or provide the home infusion network that we have available, particularly in U.S. and Europe. That's certainly a tailwind. And we actually, frankly, have not seen any impact on our compliance rates.

Therefore, the pandemic didn't really impact the current patient retention and compliance rates at all and again, we have those services available. The second part of your question, in regards to, how would we see the expansion, obviously, when the cardiomyopathy indication is received.

Obviously, that's something we are always exploring and making sure that we have the ability to be able to communicate effectively to healthcare professionals about earlier indications. But that's something, obviously, we need to continue to plan for. Let me turn it over to Andy, if he has anything to add..

Yeah. Thanks. Thanks, Tolga. I think you got it right on the home infusion. We've got that essentially quote unquote running smoothly and maxed out on our commercially insured patients and where they choose. Many are taking advantage of that.

And then on the Medicare side, obviously, the rule that was passed last year, isn't exactly the favorite of hospitals and some physicians, but we've been able to take advantage of that where we can.

I will say our ability to get folks infused at the common locations infusion centers, hospitals, et cetera, is great, and many patients frankly choose that as a route of preference for the social dynamic, or they just don't want somebody in their house.

And on the second one -- was your question on HELIOS-A in neuropathy or HELIOS-B in cardiomyopathy?.

No, it's ….

Yeah. It actually was for HELIOS-A. I'm just wondering if you are planning any commercial expansion just for vutrisiran and FAP even before your cardiomyopathy labels that come online..

Got it. And as you know, right, overlapping labels with ONPATTRO, and while we're not exactly releasing any plans on that front. We love the promotional efforts we've got out there today and are really excited about what HELIOS-A is going to bring to our portfolio..

Great. Okay. Good. Thank you, Ritu. We should move on to the next question I think..

Thank you. Our next question comes from the line of Anupam Rama from JPMorgan. Your line is now open..

Good morning. This is Tessa on the call for Anupam. Thanks for taking our question. As you consider launch dynamics between GIVLAARI and OXLUMO, what are the similarities and differences worth considering here? And then second part of the question is on GIVLAARI, anything more granular you can provide on your assumptions around 2021 U.S.

versus the rest of world growth in 2021 versus 2020. Thanks so much guys..

Okay. Thank you, Tessa. Those are great questions. Obviously, I think we covered GIVLAARI as an introduction earlier. We're excited about this year as being the second full year of launch for that important medicine.

And then in the case of OXLUMO, which only got approved in November of last year for the treatment of primary hyperoxaluria, this will be the first full year of launch. So, that's an exciting milestone. So, let's go to Tolga to answer this great question..

Sure. Thanks, John. Yeah. I mean, look, if you look at those -- both of those products and what they are really addressing, both diseases are highly rare and both diseases are highly devastating. And as John indicated, we had an excellent full year of launch with GIVLAARI during the pandemic.

And we've been able to capitalize on a lot of patients that have been waiting for this therapy. And we look -- we're probably going to be looking at the same type of dynamic with OXLUMO, with obviously relevant prevalent number of patients across the world.

Therefore, from a business model perspective, the condition that those patients are in, we expect a very similar uptake when it comes to OXLUMO..

Great. And Andy ….

I was just -- Andy, I was going to add. I guess one of the main differences here is that OXLUMO is going to be treating a lot of pediatric patients. And I also see patients with different population that needs to be addressed. But sorry -- Andy, over to you..

Yeah. The only thing I would add here is the level of excitement we are seeing right now in the PH1 communities, physicians, patients, patient advocacy groups, et cetera, is just incredible and frankly matches that we saw with GIVLAARI a year ago. So, we're off to a really, really good start.

And as Yvonne mentioned here, this is a more so pediatric population than we saw with GIVLARRI early..

Terrific. So I think we have time for one more question..

Thank you. Our next question comes from the line of Gena Wang from Barclays. Your line is now open..

Thank you for taking my question. So, I have a one big picture question. For Alnylam, we know -- no doubt Alnylam is a clear leader in RNAi space. And you've done so much work identifying the best targets and candidates and some already come to fruition.

Would you be willing to leverage this knowledge to the other technology platform, such as gene editing space and things we could see some synergy there..

Yeah. Thanks, Gena. I mean, look, we are excited about the many, many prospects we have with RNAi for the foreseeable future. We have a ton of wood to chop with this science and this technology and the type of innovation that we can bring forward really is boundless.

Now, we're always going to look at other types of technologies and how they might complement what we're doing, especially for -- especially in areas where we have a commercial presence where we might want to -- obviously think about ways to strengthen and expand our leadership beyond maybe just an RNAi based approach.

So, we'll certainly look at that. But in terms of product engines to speak of, what we have in front of us right now is just boundless from the number of opportunities, and we're very flush with things. Let me turn it over to Yvonne also to provide some additional color on that question as well.

Yvonne?.

Yeah. No, that's great, John. Yes. So we do keep a careful watch on what's going on outside Alnylam as well, for sure. I think one additional point to make on gene editing that's probably where you were going, I think, this approach has a lot of potential for patients, I think it is still in the very early stages of clinical development.

There's a lot that we need to learn about long-term durability and efficacy and safety, et cetera. So, we continue to stay engaged and be aware of what's going on. But as John says, we have an awful lot to do with what we have in our hands at the moment..

Terrific. Thank you, Yvonne. Agree.

So I think that's the last question, right, Christine?.

Correct..

Okay. Good. All right. So, let me then just close. I want to thank everybody for joining us on the call. We're obviously very pleased with our results for the fourth quarter. And what we did in 2020 was a remarkable year, despite the headwinds from COVID-19.

But we're now on a new chapter with Alnylam P5x25, aiming to build the top five company in market capitalization over the next five years, with remarkable science and technology and innovation. So, thank you all and have a great day. Bye-bye now..

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. .