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Edited Transcript of ALNY earnings conference call or presentation 6-Aug-19 12:00pm GMT

Q2 2019 Alnylam Pharmaceuticals Inc Earnings Call

Cambridge Aug 12, 2019 (Thomson StreetEvents) -- Edited Transcript of Alnylam Pharmaceuticals Inc earnings conference call or presentation Tuesday, August 6, 2019 at 12:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Akshay K. Vaishnaw

Alnylam Pharmaceuticals, Inc. - President of Research & Development

* Barry E. Greene

Alnylam Pharmaceuticals, Inc. - President

* Christine Regan Lindenboom

Alnylam Pharmaceuticals, Inc. - VP of IR & Communications

* Jeff Poulton

* John M. Maraganore

Alnylam Pharmaceuticals, Inc. - CEO & Executive Director

* Manmeet Singh Soni

Alnylam Pharmaceuticals, Inc. - Senior VP, CFO & Principal Accounting Officer

* Yvonne Greenstreet

Alnylam Pharmaceuticals, Inc. - Executive VP & COO

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Conference Call Participants

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* Alethia Rene Young

Cantor Fitzgerald & Co., Research Division - Head of Healthcare Research

* Anupam Rama

JP Morgan Chase & Co, Research Division - VP and Analyst

* David Neil Lebowitz

Morgan Stanley, Research Division - VP

* Edward Andrew Tenthoff

Piper Jaffray Companies, Research Division - MD & Senior Research Analyst

* Huidong Wang

Barclays Bank PLC, Research Division - Research Analyst

* Ritu Subhalaksmi Baral

Cowen and Company, LLC, Research Division - MD and Senior Biotechnology Analyst

* Vincent Chen

Sanford C. Bernstein & Co., LLC., Research Division - VP

* Whitney Glad Ijem

Guggenheim Securities, LLC, Research Division - Senior Analyst of Biotechnology

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Presentation

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Operator [1]

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Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals conference call to discuss second quarter 2019 financial results. (Operator Instructions) Please be advised that this call is being taped at the company's request.

I would now like to turn the call over to the company. Please go ahead.

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Christine Regan Lindenboom, Alnylam Pharmaceuticals, Inc. - VP of IR & Communications [2]

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Good morning. I'm Christine Lindenboom, Vice President of Investor Relations and Corporate Communications at Alnylam. With me today on the phone are John Maraganore, Chief Executive Officer; Barry Greene, President; Akshay Vaishnaw, President of R&D; Manmeet Soni, Chief Financial Officer; Yvonne Greenstreet, Chief Operating Officer; and Jeff Poulton, who will assume the role of Chief Financial Officer effective July 13 (sic) [August 13]. For those of you participating via conference call, the slides that are available via webcast can also be accessed by going to the Investor page of our website, www.alnylam.com.

During today's call, as outlined in Slide 2, John will provide some introductory remarks and provide general context. Barry will provide an update on our commercial and medical affairs progress, Akshay will review recent clinical updates, Manmeet will review our financials, Jeff will comment on some of his perspectives and priorities as our new incoming CFO, and Yvonne will provide a brief summary of upcoming milestones before we open the call to your questions.

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 those forward-looking statements as a result of various important factors, including those discussed in our most recent quarterly updates on file with the SEC. In addition, any forward-looking statements represent our views only as 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.

And with that, I'll turn the call over to John.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [3]

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Thanks, Christine, and thank you, everyone, for joining the call this morning. In the second quarter of 2019, we continued strong execution across both our commercial and R&D objectives. Barry will get into the details on our commercial and medical affairs progress but in a high level, as we approach the 1 year anniversary of the ONPATTRO launch and approval, we continue to be very pleased with the ONPATTRO uptake, with over 500 patients on commercial drug at the end of the second quarter. Importantly, we continue to see opportunity for steady and continued revenue growth in the quarters and years to come driven by new patient finding, global expansion and near to midterm evidence-generation activities. Moreover, advancement of Phase III development activities for fitusiran and vutrisiran into the entirety of hereditary and wild-type ATTR amyloidosis is expected to expand our opportunity significantly. And of course, our revenue growth is not just about our ATTR program alone since we have a broader portfolio of late-stage assets, including a program in registration.

We also made excellent progress against our R&D goals. Akshay will cover this in more detail, but with positive givosiran Phase III results and completed regulatory submissions, we believe we're poised for approvals in the U.S. and Europe and launches of our second product early next year, assuming positive regulatory reviews. Just yesterday, we announced that the FDA has granted givosiran a priority review with a February 4 PDUFA date and no need for an end term.

In addition, we're now positioned for 2 additional Phase III program readouts by the end of the year starting with inclisiran, our PCSK9 program licensed to the medicines company which we'll read out in the next few weeks; and then lumasiran, our wholly-owned primary hyperoxaluria RNAi therapeutic program. And to enable longer-term growth in a capital-efficient manner, we completed our largest ever partnership with Regeneron to build an industry-leading pipeline of innovative medicines focused on ocular and CNS diseases where we see significant opportunities for RNAi therapeutics. Furthermore, with the substantial funding from our Regeneron alliance, we believe our balance sheet has the stride to support a multiyear horizon for business execution.

Based on all our commercial and R&D progress and near-term prospects, we couldn't be more excited about Alnylam today, and we believe that we have a clear line of sight for our Alnylam 2020 goal of being a global, multiproduct, half-year biopharma company with a deep clinical pipeline to bolster continued growth and a robust product engine to fuel future innovation, a profile rarely, if frankly, ever, achieved in biotech. All this sets up an incredibly important period in the Alnylam story.

On the one hand, we believe that our modular reproducible and very importantly, organic platform for innovative medicines is hard to match, where, for many reasons, we believe our return on investment exceeds industry norms. And now having achieved a landmark approval of the first-ever RNAi therapeutics and having built a global and leverageable commercial capability to generate revenue growth, we have greater confidence than ever in our ability to deliver on the commercial promise of RNAi.

At the same time, we know that some of our stakeholders are eager to hear how revenue growth and continued investment in our innovative pipeline will support the path to a self-sustainable and attractive financial profile for Alnylam in the coming years. For these reasons, I'm very excited to have Jeff Poulton, our incoming CFO, join our team to help us navigate through this important transition growing Alnylam for the future. Jeff will make some comments later in the call. I'd also like to thank Manmeet Soni for everything he has contributed to -- for our company and the foundation that we built together to support our Alnylam 2020 aspirations.

Now before I turn the call over to Barry, I would like to mention that we are planning to hold an R&D Day in New York City on the morning of Friday, November 22, where we will plan to recap our latest progress in advancing our pipeline of RNAi therapeutics. We very much hope that you'll be able to join us in person or on the webcast.

So with that, I'll now turn the call over to Barry to review our commercial and medical affairs progress in more detail. Barry?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [4]

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Thanks, John, and good morning, everyone. I'll begin by reviewing ONPATTRO's commercial performance in the second quarter. We achieved $38.2 million in global ONPATTRO net product revenues in the second quarter. As in the first 2.5 quarters of launch, the majority of revenues stem from U.S. sales, and we're now pleased, for the first time, to provide more color on the geographic split, with $10 million from the EU and $28.2 million coming from the United States.

As of June 30, over 500 patients worldwide were receiving commercial ONPATTRO treatment. We're quite pleased with the overall growth and continued global demand this quarter, even with increasing product options from recent market entrants and the availability of investigational drugs through expanded access programs and investigational clinical trials. As a reminder, there have been 3 sources of patients in our launch to date: patients from our expanded access program or EAP, patients who are known to sites and new de novo patients. In the first couple of quarters of launch, we effectively captured the first 2 sources, and we're now very much into the de novo patient pool, particularly in the United States. Now when you include patients in clinical trials in our global EAP, that number increased to greater than 750 patients worldwide who are now being treated with patisiran. We believe that we're on track to have approximately 1,000 patients on ONPATTRO across commercial, clinical studies and our expanded access program by the year-end 2019, a very exciting milestone in our overall efforts.

Let me now turn to the U.S. market dynamics. On the physician front, we're seeing continued growth in both the number of new prescribers as well as repeat prescribers. In fact, over 50% of the prescriptions received in second quarter came from new prescribers. We believe new prescribers will continue to increase as health care provider disease awareness grows, fueled by multiple players engaged in disease state awareness and education.

Regarding the mix of prescribers, we continue to see about 50% of the U.S. start forms come from cardiologists, which we believe indicates strong recognition of the mixed phenotype and the awareness of polyneuropathy in this population. Additionally, we're seeing greater numbers of new prescriber specialties, like primary care and hematology, as disease awareness increases outside of the expert centers. Positive experience from patients and health care providers with ONPATTRO also continues to be a highlight and, of course, is the key predictor for future use. Speed-to-therapy also continues to improve, and overall persistence and adherence are very strong today.

Regarding U.S. market access. As reported by external coverage reports, we're very pleased that we now confirm the access to ONPATTRO and prescribe for more than 98% of U.S. lives across commercial, Medicare, Medicaid and other government payer categories. We continue to effectively partner with U.S. payers and have avoided the payer headwinds reported in this space and often reported with orphan disease launches. We're proud of this result in a very complex U.S. market access environment and believe it reflects a constructive, collaborative and productive approach, including the use of value-based agreements or VBAs we've adopted with the payer community.

Now turning to the EU and more broadly, our Canada, Europe, Middle East and Africa or CEMEA region, we're very pleased with ONPATTRO's performance in the region. As we noted earlier, we achieved $10 million in EU net product revenues during the second quarter. Some notable achievements during the quarter include favorable and competitively differentiating technology assessments in Germany, France and Italy. A highlight of the period was achieving the pricing agreements with NICE in England and with pricing authorities in Scotland. We also received marketing authorization approval in Canada where ONPATTRO is now available for commercial use. The direct reimbursement, named patient sales or reimbursement expanded access, we're now selling ONPATTRO in over 10 countries in the CEMEA region. Given the timing of pricing and reimbursement discussions in CEMEA, we expect continued market access-based growth in a number of commercial ONPATTRO patients for the rest of 2019 and into 2020. In addition to growth coming from patient finding and utilization where patients may experience inadequate response for other products for disease progression and tolerability.

Turning to our commercial progress outside the United States and CEMEA, we recently received marketing authorization approval for ONPATTRO in Japan. We're preparing for a launch in Japan and also advancing our plans to submit for regulatory approval in Brazil while exploring nonpatient sales in Latin America countries. Given the presence of endemic disease and a favorable reimbursement environment, we expect Japan, after the U.S., to be our second largest country in revenues and patients on drugs exiting 2020. As more countries around the world come online, we expect this to be an additional driver of future growth.

Our team also remains committed to addressing the challenge of raising disease awareness and improving diagnosis in ATTR amyloidosis. Improved medical education and diagnosis will help patients reach treatment options faster. The data are clear that when patients receive treatment earlier in the disease course, it improves their overall prognosis.

Now regarding patient diagnosis, as we've highlighted previously, our Alnylam Act program, available in the U.S. and Canada, is a third-party genetic screening initiative aimed at facilitating diagnosis of patients suspected of having hATTR amyloidosis. As of July, over 15,000 samples have been submitted and over 1,000 patients with pathogenic mutations have been identified with a sustained hit rate of 6% to 8%. Since there are other sponsored genetic testing programs and HCP is also a reimbursed genetic test, Alnylam Act represents only a portion of the genetic testing. We're also pleased now to partner with 23 [ME] health customers of their consumer genetic service learn more about their genetic risk of the 3 most common TTR variant in the United States.

In summary, with ONPATTRO achieving approval and access in more and more countries, with improving diagnosis and patient finding and with continued evidence-generating efforts highlighting the differentiated features of ONPATTRO, we're encouraged to see continuous and steady growth, and we're confident in our future commercial potential, even in an increasingly competitive environment. As I previously mentioned, with more companies in the ATTR amyloidosis market, we believe overall awareness will continue to accelerate, and we're enthusiastic about the benefits this will confer to patients. Moreover, as we look at the broader time horizon, we believe there are significant growth opportunities for our overall ATTR franchise, including through potential label expansion for ONPATTRO in both hereditary and wild-type ATTR amyloidosis patients with cardiomyopathy and also with the advancement of vutrisiran, our once quarterly subcu investigational RNAi therapeutic, into potentially all segments of the ATTR amyloidosis market. We're very committed to being the leaders in ATTR amyloidosis space, and we believe our efforts position us well in the future.

Finally, let me briefly turn to givosiran, which is now under active review by both U.S. and European regulators. This has been positive decisions by both agencies. We expect givosiran will launch in the U.S. and CEMEA in early 2020.

In the meantime, we're leveraging the capabilities built from ONPATTRO launch in commercialization and following the best practices developed country by country. Our team is focused on improving awareness and diagnosis of acute hepatic porphyria in the ATT and patient communities and laying the groundwork for a successful launch. As part of these overall efforts, we've launched our AHP physician and patient-focused websites to give patients resources and education materials about their disease and to provide HCPs with content and tools to help them recognize the signs and symptoms of AHP and to help them navigate the appropriate tests to arrive in an accurate diagnosis. The Alnylam Act can provide access to genetic testing at no charge for individuals in U.S. or Canada who may carry a gene mutation known to be associated with AHP. While this program for AHP is in the early stage, we can report 479 tests submitted and 51 patients with AHP mutations as of July, accounting for approximately 10% hit rate.

There's a very clear unmet need and significant burden of disease in acute hepatic porphyria. Assuming positive regulatory reviews, we're very excited with the new treatment options we can bring to patients and the associated commercial opportunity for givosiran. We look forward to the possibility of delivering this medicine to AHP patients early next year. As we've said in the past, it's our belief that this can be attractive, ultrarare orphan disease opportunity with over $500 million in global peak revenue potential. As with ONPATTRO and other orphan drug launches in underdiagnosed populations, we expect givosiran to show a consistent and steady pattern of revenue growth after launch.

With that, I'll now turn over to Akshay to review our recent R&D and pipeline progress. Akshay?

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Akshay K. Vaishnaw, Alnylam Pharmaceuticals, Inc. - President of Research & Development [5]

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Thanks, Barry, and good morning, everyone. In the interest of time, I'm going to limit my prepared remarks on our multiple Phase III clinical programs. We'll have a richer opportunity to touch on our broader pipeline later in the year and on R&D Day as John mentioned earlier.

Let me start with patisiran, which is the unbranded name for ONPATTRO. At the Peripheral Nerve Society meeting in June, we presented new 12-month interim results on the ongoing global open-label expansion study of patisiran showing sustained improvement in neuropathy impairment and quality of life for patients after 30 months of treatment. These promising new results also showed the importance of treating patients early as possible to minimize the advancement of disease. The newly presented data also in our view, showed what we believed to be a continued and favorable differentiation profile for patisiran, including the results in patients who experienced progression onto families prior to initiating treatment with patisiran, with the caveat, of course, that there be no head-to-head studies comparing patisiran with other agents. We now look forward to advancing the evaluation of patisiran in the APOLLO-B Phase III study aimed at expanding the ONPATTRO label to include cardiomyopathy in both the inherited and wild-type ATTR amyloidosis market. We're on track to start this study later this year and in positive, we will seek regulatory support for an expanded label for patisiran in the '21 to '22 time frame.

As you know, we're also advancing vutrisiran, which is delivered by quarterly subcutaneous injection, and is also a development for ATTR amyloidosis. While we've been enrolling hATTR patients with polyneuropathy in the ongoing HELIOS-A Phase III study with vutrisiran, we are pleased to announce today that we've obtained regulatory alignment on the design of HELIOS-B. HELIOS-B will be a Phase III study of vutrisiran in inherited and wild-type ATTR amyloidosis patients with cardiomyopathy. The primary end point will evaluate vutrisiran's impact on cardiovascular hospitalization and mortality. For competitive reasons, we'll await providing further details until the study starts later this year. If successful, HELIOS-B should allow vutrisiran to enter the very large wild-type ATTR amyloidosis market opportunity with clinical outcomes data.

Let's move on to givosiran, our investigational RNAi therapeutics in development for treatment of acute hepatic porphyrias. In April, we presented the complete positive results from the ENVISION Phase III study. Givosiran demonstrated robust treatment effect in significantly reducing the analyzed rate of composite attacks in AHP patients relative to placebo. Specifically, givosiran met the primary efficacy end point with a 34% mean and 90% median reduction relative to placebo in the analyzed rate of composite porphyria attacks in patients with AIP over 6 months.

Turning to safety and tolerability results. AEs were reported in 89.6% of givosiran patients and 80.4% of placebo patients in the pivotal study. Serious adverse events were reported in 20.8% of givosiran patients and 8.7% of the placebo group. While patients with givosiran, as previously mentioned, discontinued treatment due to an AE. Three assays in the givosiran group were reported as related to study drug, a single case each of pyrexia, abnormal liver function test and chronic kidney disease. We were very pleased in the second quarter to complete the rolling submission of the NDA with the U.S. FDA and to submit the MA with the European Medicines Agency. And we announced just yesterday that both applications had now being accepted and that the FDA has granted a priority review setting a PDUFA date of February 4, 2020. The FDA has also indicated that they do not foresee a need for an advisory committee meeting at this time.

Finally, with respect to givosiran, we've now enabled an expanded access program to potentially make givosiran available to qualified AHP patients following request from health care providers.

I'll now turn to recent progress with lumasiran, an investigational RNAi therapeutic in development for the treatment of primary hyperoxaluria type 1 or PH1. At the oxalosis and hyperoxaluria foundation meeting in June, we presented final results from a Phase I/II study and interim data from the Phase II OLE study of lumasiran. In these studies, we continue to see robust level of urinary oxalate to normal or near-normal levels and an encouraging tolerability profile. As you know, we're now conducting the ILLUMINATE-A Phase III study of lumasiran. This is a randomized, double-blind placebo-controlled study in PH1 patients ages 6 or older with mild to moderate renal impairment. We completed enrollment in this pivotal trial and remain on track to report top line results from ILLUMINATE-A in late 2019 and, if positive, to submit regulatory filings beginning in early 2020. Also in the second quarter, we initiated ILLUMINATE-B, a Phase III study of lumasiran in PH1 patients under the age of 6. We plan to start a third Phase III trial ILLUMINATE-C in PH1 patients with severe renal impairment later this year.

In addition to progress we've made with our wholly- and late-stage assets, our partners at The Medicines Company and at Sanofi have also been advancing our partnered Phase III assets. In May, The Medicines Company reported interim results from the ongoing ORION-3 OLE study of inclisiran, an Investigational RNAi Therapeutic Targeting PCSK9, demonstrating sustained lowering of LDL cholesterol by more than 50% with no material safety issues observed in the study. We now look forward to seeing top line results from the inclisiran ORION-11, then 9 and then 10 pivotal studies starting in the second half of the third quarter. And have been encouraged by the more than 3,500 patient-years of safety data from the Phase III program that have been reviewed on 7 separate occasions by the Independent Data Monitoring Committee with no recommended changes to study conduct. Notably, this is the largest human experience for an investigational RNAi therapeutic and positive results, if achieved, will be an important milestone for the entire field.

So with that, let me now turn the call over to Manmeet to review our financials. Manmeet?

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Manmeet Singh Soni, Alnylam Pharmaceuticals, Inc. - Senior VP, CFO & Principal Accounting Officer [6]

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Thanks, Akshay, and good morning, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the second quarter of 2019. I would like to take this opportunity to provide a brief overview of 3 key areas: our cash position, our second quarter 2019 results and our updated 2019 financial guidance.

Let me start with our cash balance. We ended the second quarter with a strong balance sheet of approximately $1.97 billion in cash, cash equivalents, marketable debt securities and restricted investments. Our cash balance includes proceeds of $800 million received in the second quarter attributed to our Regeneron collaboration.

Moving now to our revenues. Total second quarter revenues were $44.7 million. We recorded $38.2 million of ONPATTRO net product global revenue during the second quarter of 2019, which represents 45% growth from first quarter net product global revenues of $26.3 million. Our global gross-to-net or GTN percentage during the second quarter of 2019 was in mid-20s.

Cost of goods sold was $4.3 million for the second quarter, which is approximately 11% as a percentage of net product revenues. We recognized $6.5 million of collaboration revenue during the second quarter of 2019 as compared to $29.9 million during the second quarter of 2018. As expected, the decrease in collaboration revenues is primarily due to a decrease in reimbursed collectivities in connection with our collaboration agreements with Sanofi Genzyme and Vir.

Moving to other operating cost and expenses. GAAP R&D expenses were $163.9 million for the second quarter of 2019 as compared to $137.6 million for the second quarter of 2018. Non-GAAP R&D expenses were $148.6 million as compared to $126 million for the second quarter of 2018. The increase in non-GAAP R&D expenses was due to increased license fees related to our collaboration agreement with Regeneron and increased compensation expenses and facility expenses as a result of growth in the number of our late-stage programs and higher head count and clinical file expenses during the period as we continue to expand and advance our development pipeline. This increase was offset by a decrease in manufacturing expenses related to reduced batches of drug substance and raw materials.

Turning to SG&A. GAAP SG&A expenses were $112.8 million as compared to $84.7 million for the second quarter of 2018. Non-GAAP SG&A expenses were $97.4 million as compared to $74.1 million for the second quarter of 2018. The increase in non-GAAP SG&A expenses was due primarily to an increase in commercial and medical affairs head count in connection with the continued global launch of ONPATTRO. We are pleased today to have updated our 2019 annual non-GAAP R&D expense guidance to be in the range of $550 million to $575 million compared to our previously guided range of $550 million to $590 million. We are also pleased to have tightened our 2019 annual non-GAAP SG&A expense guidance to be in the range of $390 million to $400 million as compared to our previously guided range of $390 million to $410 million.

Finally, on a personal note, today is my last earnings call with the Alnylam team. I have thoroughly enjoyed my time as part of the team, and I'm proud of the many contributions made to the launch of the company as a commercial enterprise and support its global expansion across multiple geographies. I'm confident that the foundation created over the past few years will serve Alnylam well for many years to come. I've also enjoyed working with Jeff Poulton on the CFO transition.

I will now hand it over to Jeff to highlight some of his perspectives. Jeff?

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Jeff Poulton, [7]

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Thanks, Manmeet, and thanks to your help in the transition. I'd like to make just a few brief remarks as I prepare to formally assume the CFO role next week. I'm very excited to be joining Alnylam at this stage in its growth as it establishes its global commercial operations. I'm really impressed with Alnylam's technology and team and the company's potential to make a difference in patients' lives with this new frontier of medicine. I strongly believe that with its first commercial product today, prospects for many more commercial products in the coming years beginning in 2020, and a deep clinical pipeline and robust and organic product engine for the future, Alnylam is positioned to emerge as a top tier biopharmaceutical company.

Consistent with John's earlier comments, the key focus for me will be working with my new colleagues to create a road map, the financial self-sustainability, as Alnylam becomes a successful global commercial organization with significant top line growth fueled by a deep R&D pipeline. I look forward to this challenge and communicating our plans in the future.

With that, I'll now turn the call over to Yvonne to review our goals for the remainder of the year. Yvonne?

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Yvonne Greenstreet, Alnylam Pharmaceuticals, Inc. - Executive VP & COO [8]

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Thanks, Jeff, and welcome to the team. We couldn't be happier to have you on board.

I'm really thrilled to the progress we've made in 2019 so far, but we still have a number of exciting milestones to look forward to in the remainder of the year.

For starters, we plan to continue our global commercialization of ONPATTRO, including launching in Japan and other countries. We also look forward to initiating the APOLLO-B Phase III study in mid-2019, aimed at securing an expanded commercial label for patisiran to include wild-type and hereditary cardiac amyloidosis. With vutrisiran, we plan to continue enrolling the HELIOS-A Phase III trial throughout the year and expect to initiate HELIOS-B, an outcome study, in wild-type and hereditary ATTR cardiac amyloidosis patients in late 2019. With givosiran, we plan on having additional data from ENVISION presented at the ICPP meeting in early September.

Turning to lumasiran, with enrollment in the ILLUMINATE-A Phase III study now complete, we plan to report top line results from that study in late 2019. We will also continue enrolling pediatric patients in ILLUMINATE-B and plan to start the ILLUMINATE-C study in PH1 patients with severe renal impairment later in 2019.

With inclisiran, we expect our partners at The Medicines Company to report top line results from the ORIONs 9, 10 and 11 studies beginning later this quarter and assuming positive data to submit an NDA for inclisiran by the end of the year. And of course, we'll continue advancing our pipeline of earlier-stage clinical efforts as well as exciting pre-clinical efforts, and we'll highlight those milestones throughout the rest of the year as they occur. In particular, you should expect data readouts from a number of our early- and mid-stage clinical programs.

Let me now turn it back to Christine to coordinate our Q&A session. Christine?

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Christine Regan Lindenboom, Alnylam Pharmaceuticals, Inc. - VP of IR & Communications [9]

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Thank you, Yvonne. Operator, we will now open the call for questions. (Operator Instructions)

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question is from Alethia Young from Cantor Fitzgerald.

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Alethia Rene Young, Cantor Fitzgerald & Co., Research Division - Head of Healthcare Research [2]

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Congrats on the progress as you continue this launch. Just one from me, maybe and it has a little bit of a follow-on twist, but can you just talk a little bit about tafamidis and what you're seeing and hearing from how doctors make decisions and like 50% of your doctors are cardios? And then just kind of tagging onto that, can you talk a little bit more about how the presence of both the Amgen drug and the Pfizer drug have driven diagnosis? Can you give any top quantitive metrics or is there any other color you can give us around that?

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [3]

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Right. Thanks, Alethia. Barry, you want to handle it?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [4]

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Yes. So Alethia, we -- on the merging landscape, it's too early to give specifics around increased diagnosis and increased speed of diagnosis, other than the color that we are gaining more and more new prescribers every quarter, which is a sign that new people are learning about the disease, seeing the disease and then are comfortable diagnosing and holding onto their patient. So anecdotally, we're definitely seeing the increase of awareness. And having multiple players at every cardiology congress educate that there's the disease of hATTR amyloidosis has certainly been helpful for patients in raising awareness.

Now on tafamidis specifically, again, it's too early in their launch to understand the particular dynamics. What our market research is telling us is that physicians who understand hereditary ATTR amyloidosis, even in those mixed phenotype with polyneuropathy, ONPATTRO is the drug of choice, particularly in the United States. And then for those that are wild-type, clearly, tafamidis is a choice. In Europe, where tafamidis has been present for a number of years, physicians understand the progression of tafamidis and we're seeing a number of patients that are switched, hereditary patients from tafamidis onto ONPATTRO in the major markets where tafamidis has been used. So does that answer your question, Alethia?

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Alethia Rene Young, Cantor Fitzgerald & Co., Research Division - Head of Healthcare Research [5]

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Yes.

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Operator [6]

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We'll go next to Gena Wang from Barclays.

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Huidong Wang, Barclays Bank PLC, Research Division - Research Analyst [7]

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First one also regarding the ONPATTRO commercial question. For all the 500 patients on commercial drugs, how many were from XUS? And also following Alethia's question, 49% demand from cardiologists, how is the payer coverage for these patients?

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [8]

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Great. Let me quickly address the first one and then I'll hand it over to Barry for the second one. We're not breaking out patient numbers by region. We are, for the first time, breaking out revenues and we're reporting $28.2 million in the U.S. and $10 million in rest of world, CEMEA in this case. So that's unfortunate we're limited for really competitive reasons. Barry, you want to answer the second question?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [9]

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Yes. In terms of U.S. payer coverage, which we reported, I mean we remarkably have external reports saying that 98% of our patients who are prescribed ONPATTRO will be reimbursed ONPATTRO. It's actually quite remarkable. We have not, to date, had a patient rejected by a payer.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [10]

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And just to add to that, Gena, we're of the very strong belief that the proactive and high-quality approach that we took in engaging with payers as we introduced ONPATTRO to the market and continue to have discussions with payers, even to this day around value-based agreements, these are all elements of what has, I think, been a very successful market access story for this important medicine in the U.S. market.

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Operator [11]

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And moving on, our next question will come from Whitney Ijem from Guggenheim.

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Whitney Glad Ijem, Guggenheim Securities, LLC, Research Division - Senior Analyst of Biotechnology [12]

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The first one, I guess I'm going to ask on givosiran. So the first one, in terms of the greater than $500 million for givosiran opportunity, any color you can give us on what that assumes in terms of use in sporadic versus recurrent patients, either kind of in terms of how the drug will be used or relative breakdown of patients in either bucket?

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [13]

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Sure. Great question. Maybe just for the benefit of others on the call obviously the recurrent patient population that we have estimated to be approximately 1,000 patients in the U.S. and Europe and they're about -- estimated to be 5,000 patients with sporadic disease defined as 3 attacks or less. Keep in mind that any patient that experienced an attack can experience attacks, they can be life-threatening. So it doesn't lessen the importance of their disease if they're a sporadic patient. But with that, Barry, do you want to comment a little bit about how we get to the beliefs that around -- a greater than $500 million opportunity?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [14]

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Yes. And John, you outlined it very, very well. As with many ultrarare orphan diseases where patient journeys can last 13 to 15 years and patients show up with 3 to 4 unnecessary surgery or are misdiagnosed by about a dozen physicians in their journey, we believe that there are probably many more patients than the number that John highlighted out there. An interesting fact, as little as 3 years ago, the Porphyria Consortium, which has been studying this disease for 20 years, did not have the benefit of an industry partner doing natural history. And by working with them, we've all now understood that 2/3 of patients experienced debilitating chronic pain between attacks. So as John said, it's not just about attack rate number of attacks. It's about the overall devastating nature of the disease. So when you take the 1,000 and 5,000 likely growing and multiply that by an orphan price point, we think there's a very significant opportunity. Now of course, we're going to take the same proactive nature driven by our patient access philosophy with givosiran, as we've taken with ONPATTRO, we've been very proactive with payers to ensure that we put the right value-based agreements in place, so that the patients in the United States and, frankly, around the world, have access to an important medicine for their devastating disease.

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Whitney Glad Ijem, Guggenheim Securities, LLC, Research Division - Senior Analyst of Biotechnology [15]

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Great. And one quick follow-up on ONPATTRO, any color you can give on the relative XUS price versus U.S. at this point?

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [16]

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Yes. Barry, you want to comment?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [17]

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Well, as we've highlighted on previous calls, we've held the price band very, very tight on a per vial basis. And then of course, price varies because it is weight-based dosing. So in countries with bigger people, it's more dollars per patient per year and in smaller people, it's less. But the vial price is very, very tight.

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Operator [18]

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We'll go next to Anupam Rama from JPMorgan.

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Anupam Rama, JP Morgan Chase & Co, Research Division - VP and Analyst [19]

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Congratulations on all the progress here. In the U.S., like you've outlined here, you're getting about 50% of the ONPATTRO demand coming from cardiologists. Wondering if you could provide any color on some of the OUS prescribing trends and then maybe any color on the gating factors starting HELIOS-B for fitusiran.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [20]

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Right. So let's have Barry talk a little bit about the XUS trends on prescribers and then Akshay, you can handle the next -- the second question. So Barry?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [21]

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Yes. Thanks, Anupam. As you've highlighted, we said about 50% from the U.S. prescribers are cardiologists. And interestingly enough, the number of additional specialties, including primary care physicians, nurse practitioners, is growing. A real sign that as health care providers become familiar with the disease, see a patient, they understand how to diagnose and clearly what's prescribed, at least, in our case, with ONPATTRO. In XUS, it really depends on the country. There are some countries like France that are highly coordinated with centers, and there are named centers where neurologists or cardiologists takes care of those patients. And then in places like Germany, it's primarily neurology-driven. So it really depends XUS on a country and how the centers are established. Turning to Japan, which we mentioned earlier, we believe that the primary prescribers, at least, in the initial launch in Japan, will be neurologists because those are the folks that manage the overall disease symptomology. Now of course, dynamics back to the United States, really is the V122I patient populations. So in parts of the world where patients of Western African descent, we probably will see a bigger uptake in cardiology, at least, in the hereditary space.

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Akshay K. Vaishnaw, Alnylam Pharmaceuticals, Inc. - President of Research & Development [22]

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Just following up on the HELIOS-B question. Essentially, the main gating factor was getting aligned with regulatory agencies globally. And I think we're in great shape now as we reported this morning that we're looking forward to vigorous start for that program in the second half of this year now and as you know, we know all the TTR sites globally, and we're excited to start enrolling wild-type patients as well, of course, in that study.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [23]

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Did that answer your question?

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Anupam Rama, JP Morgan Chase & Co, Research Division - VP and Analyst [24]

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Yes. Great.

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Operator [25]

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Ritu Baral from Cowen has our next question.

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Ritu Subhalaksmi Baral, Cowen and Company, LLC, Research Division - MD and Senior Biotechnology Analyst [26]

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I've already gotten a few e-mails this morning on some concerns around U.S. specific growth. I think the assumption is that the Q1 number -- the Q1 revenue number of $26.3 million was largely 95% driven by U.S. Understanding you don't want to comment on patient numbers, can you give us a little more comfort around the U.S. growth rate? Can you comment on how things like HELIOS-A enrollment, how much of an impact that's having on the launch and things like persistence -- a little more color on persistence of treatment, especially given the steroid pretreatment?

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [27]

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Yes. Ritu. First of all, I mean the concern about U.S. growth is completely wrong, actually. We've had steady growth in the U.S. and in Europe. Manmeet, you want to comment more specifically to provide support for that?

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Manmeet Singh Soni, Alnylam Pharmaceuticals, Inc. - Senior VP, CFO & Principal Accounting Officer [28]

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Sure, John. So Ritu, as John mentioned, we had consistent growth, and you saw the global revenue grew over approximately 45% from Q1 to Q2. But if I split out U.S. and Europe, U.S. was going even higher rate. U.S. was growing at a 50% rate from Q1 to Q2. So to give you numbers, which were not there and you would see them in the 10-Q filing when we file later today -- this evening or tomorrow, for U.S., last quarter Q1 was approximately $18.8 million and this quarter is $28 million. So that shows a pretty strong growth of 50%. In Europe, we were, last quarter, at $7.5 million and now, this quarter is $10 million, so that also shows a 33% growth. But as you know, there are -- in Europe, the growth comes primarily as we launch new countries and we get the final pricing and reimbursement finalize. So as Barry and John mentioned, we are showing the steady and continuous growth in our revenue and there is no concern on both U.S., Europe and global revenue growth. I just want to give on...

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [29]

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Yes. Just...

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Manmeet Singh Soni, Alnylam Pharmaceuticals, Inc. - Senior VP, CFO & Principal Accounting Officer [30]

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Sorry.

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [31]

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Yes. Go ahead.

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Manmeet Singh Soni, Alnylam Pharmaceuticals, Inc. - Senior VP, CFO & Principal Accounting Officer [32]

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No, Barry. There were some more questions on persistence, on adherence...

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [33]

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Yes. Manmeet, I think you covered the growth incredible. And just to emphasize, we are seeing continuous and steady growth in the United States and believe it will continue, maybe even a particular uptake in the out quarters because of awareness. In Europe, as Manmeet highlighted, we're -- in countries we're launched, we continue to see growth, and a number of new countries will come on late this year into 2020. And then Japan is coming on late this year and into 2020. So we do see new market entrants and then within each country, steady growth within country. So that dynamic will continue. You asked about continuation, we see tremendous continuation of patients on ONPATTRO. Anecdotally, we hear tremendous reports about physician experience and patient experience, and the adherence rate remains very, very high. Still way early into our launch to give specific numbers, but it remains very high.

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Akshay K. Vaishnaw, Alnylam Pharmaceuticals, Inc. - President of Research & Development [34]

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And just to follow up on that, Ritu. The APOLLO study itself, the very low dropout rate there, the high conversion rate to the OLE -- the persistence in the OLE, it is all evidence that the risk/benefit is being well tolerated and patients are staying on drug. We know from OLE patients who've been on drug from 2013, '14 onwards actually from the original Phase II and then the Phase III, we're 5 years into it. So the earlier comment, I don't think applies, and we have very good evidence accumulating now that patients are tolerating this direct preregimen well, which, by the way, over the years, the dose has been considerably reduced as well.

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Ritu Subhalaksmi Baral, Cowen and Company, LLC, Research Division - MD and Senior Biotechnology Analyst [35]

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The impact of HELIOS-A on that as well, on the launch, enrollment of HELIOS-A on the launch.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [36]

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Yes. I mean look, I mean as we've said from the beginning obviously HELIOS-A patients are potential ONPATTRO patients. We know that. And there -- for every patient that goes into HELIOS-A, they could be a commercial patient, of course, we understand that. But we're investing in that program for the benefit of having a new product offering for patients in the future, in the not-too-distant future, that we think will continue to drive growth of the franchise. So it is obviously a very eyes-wide-open type of decision to do that. Now we are importantly expanding, just this past quarter, significantly the sites outside the U.S., and we are going to see the benefit of that in countries and markets where there is no reimbursement at the present time. So that will obviously dilute out any attack that might occur on the commercial ONPATTRO growth from clinical studies.

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Operator [37]

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We'll take our next question from Paul Matteis from Stifel.

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Unidentified Analyst, [38]

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This is Nate on for Paul. Maybe just a quick one on the 1,000 patients by year-end guidance. How are you getting confident in that number in terms of the de novo patient growth rate that you're seeing sequentially? And then quick to clarify, does that 1,000, is that commercial drug or does that include patients in expanded access programs?

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [39]

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Yes. It includes patients in our expanded access program and also in our ongoing open-label study. So we do believe that we're on track to achieve that. We're roughly, at this point, over 750 patients within that universe. And we're very much on track to hit that over 1,000 -- approximately 1,000 patient number by the end of the year. So that's encouraging.

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Unidentified Analyst, [40]

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Great. And then the de novo patient growth rate, just, I don't know if you can provide much detail on that subsegment.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [41]

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Well, I mean Barry can comment as well, but let's -- when we talk about growth, let's be clear we understand the buckets of growth. What is new patient finding, de novo patients being identified, and you could look at Alnylam Act. We're getting about a couple thousand samples per quarter, and we're finding roughly 150-or-so patients per quarter. And that's been very, very steady now for over a year of that program. Now those aren't necessarily ONPATTRO patients. This is just a number that you can look at as a surrogate marker, if you will, for patient finding. But patient finding is ongoing. And as Barry said earlier, it's not just Alnylam Act, it's other testing programs that are out there, some funded by companies, some that are not. So there really is a significant amount of new patient finding happening, and by the way, that's just in the U.S., right, in Canada as well. So it doesn't reflect new patient finding around the world, which is also getting better. So that's one source of growth.

The second important source of growth is our global expansion. And also in Europe, it's the expansion of market access on a country-by-country basis. And that's a very important source of growth. Barry commented earlier around Japan, which we believe by the end of 2020 will be our second largest market. And that's going to be an important source of growth, in addition to what's going on in the U.S. and what's going on in Europe and the rest of the world.

And the final source of growth, which I think it points to the -- what we believe to be a remarkable profile of ONPATTRO is the evidence-generation activities that our medical affairs team and for longer term, our clinical development team are engaged in to really strengthen the differentiation of ONPATTRO to help patients understand or physicians understand the best time to use ONPATTRO for their patients to help highlight some of the issues that may exist with other therapies that are out there, like disease progression where ONPATTRO can be very helpful. Those types of activities will have both near-term and midterm implications for growth. So let me pause there. Barry, anything else to add?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [42]

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No. You covered it completely.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [43]

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Right. Thank you.

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Operator [44]

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Next, we'll go to Vincent Chen from Bernstein.

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Vincent Chen, Sanford C. Bernstein & Co., LLC., Research Division - VP [45]

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Congratulations on the progress. I was just wondering if you could provide a little more color on the folks identified in Alnylam Act with TTR amyloidosis who don't go on ONPATTRO. What are the reasons for these, recognizing it's a third-party program, whether you're certainly very plugged in with the TTR community? Could you give us a sense for how these patients break out, what portion of mutations associated with neuropathy or mixed disease versus a more pure cardiomyopathy phenotype or some ending up in trials, et cetera? Or would you expect that many of them do eventually work their way onto ONPATTRO over time? And as a quick corollary, how do the pace of new start forms look in the second quarter?

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [46]

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Yes. So maybe just a couple of quick comments and then I'll hand it over to Barry. We don't have a lot of visibility on specific patients in Alnylam Act, and that's by design. This is a program that's aimed to help physicians diagnose their patients. It's not anything other than that. And obviously, we believe that by improving medical education, improving patient diagnosis, that if ONPATTRO is identified as the right choice for treatment for these patients by their physicians, then that will follow. So that has been the philosophy. We just don't have a lot of color other than that in terms of Alnylam Act. So that's the answer to that one.

And then our start forms, as we said last quarter, we moved away from reporting start forms as is common in drug launches because the fact that it's an imprecise measure of patients. We have patients in the U.S. that come into ONPATTRO therapy outside of start forms and of course, our forms are a U.S.-specific measure to begin with. So it's not even reflecting true patient growth. The patient number is what you should focus on and obviously revenues. Barry, anything else to add to what I just said?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [47]

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No. I think you covered it well. Just back to Alnylam Act, again, just to reiterate. Alnylam Act is a free third-party genetic test that we and other companies -- other companies offer other tests for the benefit of patients. And just to give you some color about, Vincent, what we often see is that a patient will come in after a multiyear journey, finally be diagnosed with hATTR amyloidosis, and through genetic counseling, identified that they have this disease to their siblings, children and others. And those people often then will visit a physician for a genetic test. So Alnylam Act really eases the burden for the benefit of patients to get these genetic tests. As John said, it's an arm's length relationship because we're there for the benefit of patients. Now some patients do not yet have penetrance of disease, but we believe that by raising awareness -- remember, this is not about a portion of the pie, it's growing the overall pie that will continue to benefit patients by raising awareness and speed to diagnosis.

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Operator [48]

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Our next question today is from Ted Tenthoff from Piper Jaffray.

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Edward Andrew Tenthoff, Piper Jaffray Companies, Research Division - MD & Senior Research Analyst [49]

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Congrats on the progress. I'm really, really impressed with the global launch. And just to comment, I love that you guys are breaking it out globally. It really gives us a sense of where the placements are coming from and the growth is coming from. So thank you for that. Kind of looking at vutrisiran and really considering sort of how this market could evolve, tell us a little bit more about where you think sort of IV versus subcu might be used and maybe even if there would be induction versus maintenance or just give us a little bit more of a sense of how you see all of that playing out.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [50]

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Yes. Thanks, Ted, and thanks for your comments earlier. I mean we're extremely excited about vutrisiran. It's a once-quarterly low-dose, low-volume subcutaneous injection that we think is an exciting expansion of the overall ATTR opportunity. I mean taking a step back, when you think about this market, you think about hereditary ATTR polyneuropathy where we are today and then in the future, expanding into cardiomyopathy if our studies are successful. And then you think about the wild-type setting, again, with studies like APOLLO-B and HELIOS-B, assuming those studies are successful, we've got a remarkable opportunity for the overall franchise for many, many years to come. And I think without getting heady or heighty in terms of numbers, I mean this really is a multibillion type of market opportunity where Alnylam is poised to be a significant leader. So vutrisiran really positions us with a product offering that really provides a great option for patients in HELIOS-A, will bring medicines to patients quickly, rapidly. That study is up and going and rolling, we expect that to read out in the '21, '22 time period. That will be important for patients to get access to a subcu alternative like vutrisiran. And then HELIOS-B, which will start up very shortly by the end of the year, that really addresses the larger commercial opportunity and the wild-type and hereditary cardiomyopathy setting, a very, very significant opportunity with a once-quarterly subcutaneous option that we think is extremely competitive. And we've done studies that show that it's even preferred over an oral agent, given once a day or even less excitingly, twice a day. So these are really opportunities for market growth and expansion for Alnylam that is not that far away at all and very, very exciting to look forward to. So Barry, anything else to add to that?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [51]

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No. I think you covered it well. I guess the only -- 2 things. One, an interesting analog to look at is how the MS market developed over the last 30 years. And if you think 30 years ago to today and project out the ATTR amyloidosis marker over the next 10 to 15 years, we can see a dynamic where more prescribers are getting interested. Diagnosis gets much earlier in the disease and patients benefit greater by an earlier diagnosis. So just in addition to what John mentioned, I see those same dynamics playing out with ATTR amyloidosis.

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Operator [52]

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And we'll go next to David Lebowitz from Morgan Stanley.

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David Neil Lebowitz, Morgan Stanley, Research Division - VP [53]

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Could you characterize the effort it takes to transition patients that are diagnosed in the Alnylam Act program to actually being patients on drug and noticing that there are certainly more patients that are from the cardio? And I guess given that the drugs approved for polyneuropathy are coming online for the drug, what would be driving the fact that so many cardio patients are coming on?

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [54]

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Sure. Let's -- Barry, you want to handle it?

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Barry E. Greene, Alnylam Pharmaceuticals, Inc. - President [55]

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Yes. I mean more broadly, just -- again I'll just say that there's a number of things we're doing to increase awareness in diagnosis. Hereditary transthyretin amyloidosis is unfortunately a disease where patients can bump into cardiologists, neurologists, other specialties who misdiagnosed the disease, and that dynamic continues until awareness is raised. Now specifically on the cardiology front, if a patient presents with cardiovascular symptoms, there are tools that cardiologists have that are using now more and more, echo technetium scanning, that helps point to amyloidosis and specifically, TTR amyloidosis, which is why we see the cardiology community so interested. And then of course, there are many, many wild-type patients, the segment that we're not yet penetrating commercially, we will in the future, assuming positive data. And because there are so many wild-type patients, cardiologists are becoming more and more aware. Now importantly, we're also seeing on the neurology side more awareness of TTR amyloidosis, hereditary. They're looking for the disease using the tools they have. So we see that all as positive signs of improved diagnosis and speeder diagnosis.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [56]

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Right. And Akshay?

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Akshay K. Vaishnaw, Alnylam Pharmaceuticals, Inc. - President of Research & Development [57]

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Yes. I mean just to build on what Barry was saying, if we look at the U.S. landscape, in many senses, V122I is the commonest mutation. But the other important thing to bear in mind is that there's increasing awareness that a very significant proportion of those patients have neuropathy. And certainly, what Barry is seeing, I've seen when I've spoken to doctors is cardiologists are looking increasingly for neuropathy, they're collaborating with their neurologist in multifunctional teams to fully characterize the multisystemic nature of the disease. And as appropriate, if they have neuropathy, then to prescribe a relevant drug like ONPATTRO. So Barry is actually right, it's a journey, the education awareness is increasing, and it's great that patients who have V122I and other mutations are getting more fully characterized so physicians and patients understand the full burden of disease. And as I said, where appropriate found neuropathy, then certainly ONPATTRO is an important choice for them.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [58]

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Does that answer your question?

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David Neil Lebowitz, Morgan Stanley, Research Division - VP [59]

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Thank you very much. Appreciate it.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [60]

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Great. Thank you. Okay. Go ahead, operator.

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Operator [61]

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That's all the time we have for questions. I'll turn it back to the company for closing remarks.

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John M. Maraganore, Alnylam Pharmaceuticals, Inc. - CEO & Executive Director [62]

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Great. Well, thanks, everyone, for joining us on the call. We're obviously very pleased with the R&D and commercial progress that we've been making. We are really excited about the company that we're building, the impact we're making on patients' lives. So with that, I look forward to updating you on our continued progress in the coming weeks and months. Have a great rest of the day, everybody. Bye-bye.

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Operator [63]

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And that does conclude our conference today. Thank you for your participation. You may now disconnect.