Alnylam Submits Supplemental New Drug Application (sNDA) to U.S. Food and Drug Administration (FDA) for ONPATTRO® (patisiran) for the Treatment of the Cardiomyopathy of ATTR Amyloidosis

Rhea-AI Summary

Alnylam Pharmaceuticals has submitted a supplemental New Drug Application (sNDA) to the FDA for patisiran, an investigational RNAi therapeutic aimed at treating transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy. This follows positive results from the Phase 3 APOLLO-B study, which demonstrated significant improvements in functional capacity and quality of life at 12 months. The study also showed an encouraging safety profile, with most adverse events being mild to moderate. Patisiran is already FDA approved for polyneuropathy of hereditary ATTR amyloidosis.

Positive

• Submission of sNDA for patisiran to FDA for ATTR amyloidosis with cardiomyopathy.
• Positive Phase 3 APOLLO-B study results indicate significant improvement in patient functional capacity and quality of life.
• Encouraging safety profile observed, consistent with prior studies.

Negative

• None.

– sNDA Submission is Based on Findings from the APOLLO-B Phase 3 Study That Showed Patisiran Demonstrated Significant Improvement on Functional Capacity, Health Status and Quality of Life Compared to Placebo at Month 12 –

– Study Also Demonstrated Encouraging Safety Profile in Patients with Cardiomyopathy of ATTR Amyloidosis –

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced the submission of its supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for patisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy. Patisiran is the established name for ONPATTRO^®, which is currently approved by the U.S. FDA for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.

“We are excited by today’s announcement as the submission of our sNDA brings us one step closer to making patisiran available to patients with ATTR amyloidosis with cardiomyopathy. Patisiran has the potential to improve the functional capacity and quality of life of patients with ATTR amyloidosis with cardiomyopathy, an increasingly recognized cause of heart failure for which there are limited treatment options,” said Rena N. Denoncourt, Vice President, TTR Franchise Lead. “The positive results of the APOLLO-B Phase 3 study of patisiran validate the therapeutic hypothesis that TTR silencing by an RNAi therapeutic may be an effective approach to treating cardiomyopathy of both wild-type and hereditary ATTR amyloidosis. This is an important milestone as we work to build an industry-leading franchise for the treatment of ATTR amyloidosis.”

The application to the FDA was based on positive results from APOLLO-B, a Phase 3, randomized, double-blind, placebo-controlled multicenter global study that demonstrated the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The safety profile in APOLLO-B was consistent with what was observed in APOLLO and in postmarketing use of ONPATTRO. In APOLLO-B, the majority of adverse events (AEs) were mild or moderate in severity. The 12-month results from the study were presented at the 18^th International Symposium on Amyloidosis (ISA) on September 8, 2022.

ONPATTRO Indication and Important Safety Information
Indication
ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

Important Safety Information
Infusion-Related Reactions
Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation
ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).

Adverse Reactions
The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%).

For additional information about ONPATTRO, please see the full U.S. Prescribing Information.

About ONPATTRO^® (patisiran)
ONPATTRO (patisiran) is an RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. ONPATTRO is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR). It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues.

About ATTR Amyloidosis
Transthyretin-mediated (ATTR) amyloidosis is a rare, rapidly progressive, debilitating disease caused by misfolded transthyretin (TTR) proteins which accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal (GI) tract. There are two different types of ATTR amyloidosis – Hereditary ATTR (hATTR) amyloidosis, caused by a TTR gene variant, and Wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant. hATTR amyloidosis affects approximately 50,000 people worldwide, while wtATTR amyloidosis is estimated to impact 200,000 – 300,000 people worldwide.

About LNP Technology
Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.

About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding 20 years ago, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO^® (patisiran), GIVLAARI^® (givosiran), OXLUMO^® (lumasiran), AMVUTTRA^® (vutrisiran) and Leqvio^® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P⁵x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.

Alnylam Forward Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam’s views with respect to the safety and efficacy of patisiran for the treatment of ATTR amyloidosis with cardiomyopathy, the potential of treatment with patisiran to address multiple aspects of ATTR amyloidosis, including cardiac manifestations of disease, Alnylam’s commitment to develop impactful RNAi therapeutic options for patients living with all forms of ATTR amyloidosis, and Alnylam’s aspiration to become a leading biotech company and the planned achievement of its “Alnylam P⁵x25” strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylam’s business, results of operations and financial condition and the effectiveness or timeliness of Alnylam’s efforts to mitigate the impact of the pandemic; the potential impact of the January 2022 leadership transition on Alnylam’s ability to attract and retain talent and to successfully execute on its “Alnylam P⁵x25” strategy; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates, including patisiran and vutrisiran; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, including patisiran and vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its approved products globally; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to successfully expand the indication for ONPATTRO, AMVUTTRA or OXLUMO in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam’s ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the potential impact of a current government investigation and the risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

This release discusses investigational RNAi therapeutics and uses of previously approved RNAi therapeutics in development and is not intended to convey conclusions about efficacy or safety as to those investigational therapeutics or uses. Patisiran has not been approved by any regulatory agency for the treatment of ATTR amyloidosis with cardiomyopathy. No conclusions can or should be drawn regarding its safety or effectiveness in treating cardiomyopathy in this population. There is no guarantee that any investigational therapeutics or expanded uses of commercial products will successfully complete clinical development or gain health authority approval.

View source version on businesswire.com: https://www.businesswire.com/news/home/20221208005974/en/

Alnylam Pharmaceuticals, Inc.

Christine Regan Lindenboom

(Investors and Media)

+1-617-682-4340

Josh Brodsky

(Investors)

+1-617-551-8276

Source: Alnylam Pharmaceuticals, Inc.

FAQ

What is the recent sNDA submitted by Alnylam Pharmaceuticals?

Alnylam has submitted a supplemental New Drug Application for patisiran to the FDA for treating ATTR amyloidosis with cardiomyopathy.

What were the results of the APOLLO-B study for patisiran?

The APOLLO-B study showed significant improvements in functional capacity and quality of life for patients taking patisiran compared to placebo over 12 months.

Is patisiran already approved for any conditions?

Yes, patisiran is currently FDA approved for the treatment of polyneuropathy of hereditary ATTR amyloidosis.

What did the APOLLO-B study indicate about patisiran's safety?

The study indicated an encouraging safety profile for patisiran, with the majority of adverse events being mild to moderate.

What potential does patisiran have according to Alnylam?

Alnylam believes patisiran could significantly improve the quality of life for patients suffering from ATTR amyloidosis with cardiomyopathy.