Alnylam Announces Positive Outcome of FDA Advisory Committee Meeting

– Cardiovascular and Renal Drugs Advisory Committee Voted 9:3 That the Benefits of Patisiran Outweigh its Risks for the Treatment of the Cardiomyopathy of ATTR Amyloidosis –

– Prescription Drug User Fee Act Target Action Date is October 8, 2023 –

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Sep. 13, 2023– Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced the positive outcome of the U.S. Food and Drug Administration’s (FDA) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) meeting to discuss the supplemental New Drug Application (sNDA) for patisiran, an investigational RNAi therapeutic in development for the treatment of the cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis. The CRDAC voted 9:3 that the benefits of patisiran outweigh its risks for the treatment of the cardiomyopathy of ATTR amyloidosis.

“We are grateful for the CRDAC’s thoughtful review and discussion, and thank the patients, physicians and advocacy community who shared their valuable insights today,” said Pushkal Garg, M.D., Chief Medical Officer at Alnylam. “The positive outcome of today’s meeting is supported by the efficacy and safety data observed in the APOLLO-B Phase 3 study, and is another step toward bringing patients with the cardiomyopathy of ATTR amyloidosis a novel treatment option that addresses the underlying cause of disease and has the potential to meaningfully benefit patients’ functional capacity and quality of life. We look forward to continuing to work with the FDA as they complete their review of our sNDA.”

ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the heart, resulting in cardiomyopathy and heart failure. The cardiac manifestations associated with ATTR amyloidosis can have a devastating impact on patients’ lives and treatment options today are limited, with many patients continuing to progress on, or unable to access, current standard-of-care.

The positive decision by the FDA’s CRDAC panel of independent experts was based on a discussion of the data supporting the sNDA for patisiran, which include positive results from the APOLLO-B Phase 3 study that demonstrate favorable effects on functional capacity and health status and quality of life in patients with ATTR amyloidosis with cardiomyopathy relative to placebo, as measured by the 6-Minute Walk Test (6-MWT) and the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score, respectively.

The CRDAC provides the FDA with independent, expert advice and recommendations on marketed and investigational medicines for use in the treatment of cardiovascular and renal disorders. The CRDAC’s vote, while not binding, will be considered by the FDA when making its decision regarding the potential expanded indication for patisiran. The FDA has set an action date of October 8, 2023, under the Prescription Drug User Fee Act.

Patisiran is the established name for ONPATTRO^®, which is approved by the FDA for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.

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 hereditary ATTR (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. Patisiran is also being evaluated for the treatment of the cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis; the safety and efficacy of patisiran in this indication have not been established or evaluated by the FDA, EMA or any other health authority.

About ATTR Amyloidosis

Transthyretin-mediated (ATTR) amyloidosis is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy, or both manifestations of disease. There are two different forms of ATTR amyloidosis – hereditary ATTR (hATTR) amyloidosis, which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant and impacts an estimated 200,000 – 300,000 people worldwide.

About APOLLO-B Phase 3 Study

APOLLO-B is a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed and powered to evaluate the effects of patisiran on functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy. The study enrolled 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy at 69 sites in 21 countries. Patients were randomized 1:1 to receive 0.3 mg/kg of patisiran or placebo intravenously administered every three weeks over a 12-month treatment period. After 12 months, all patients received patisiran in an open-label extension period.

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 Pharmaceuticals (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 in 2002, 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), AMVUTTRA^® (vutrisiran), GIVLAARI^® (givosiran), OXLUMO^® (lumasiran), 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 X (formerly Twitter) at @Alnylam, or on LinkedIn, Facebook, or Instagram.

Alnylam Forward Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, statements, express or implied, relating to the FDA Advisory Committee’s statements and recommendations regarding the potential benefits of patisiran for the treatment of the cardiomyopathy of ATTR amyloidosis in adults, Alnylam’s plans to continue working with the FDA as they complete their review of the patisiran sNDA; that the FDA is not bound by the advisory committee recommendation but takes its advice in consideration when reviewing applications; and expectations regarding Alnylam’s aspiration to become a leading biotech company and the planned achievement of its “Alnylam P⁵x25” strategy, should be considered forward-looking statements. 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 FDA may not approve the sNDA for patisiran by the application PDUFA date or at all, we may not be able to comply with all FDA requests, including with respect to our patisiran sNDA, in a timely manner or at all; Alnylam’s ability 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 Alnylam’s 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 Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; delays or interruptions in the supply of resources needed to advance Alnylam’s research and development programs, including as may arise from recent disruptions in the supply of non-human primates; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to successfully expand the indication for ONPATTRO or AMVUTTRA 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 Roche, Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the potential risks of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2022 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q 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/20230913147234/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.

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