Alnylam Submits Supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration for Vutrisiran for the Treatment of Transthyretin Amyloidosis with Cardiomyopathy

− sNDA is Based on Full Findings from the Positive HELIOS-B Phase 3 Study –

− Priority Review Voucher Utilized to Accelerate Review Period –

− Alnylam to Host and Webcast TTR Investor Day Event Today in New York City –

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 vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). Vutrisiran is the generic name for AMVUTTRA®, which is currently approved by the U.S. FDA for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults. As part of the submission, the Company utilized a Priority Review Voucher, which obligates the FDA to an accelerated review timeline.

“We are proud that with this first regulatory submission, we are a significant step closer to bringing vutrisiran to patients with ATTR amyloidosis with cardiomyopathy, which is a steadily progressive, debilitating, and ultimately fatal disease. HELIOS-B demonstrated rapid knockdown of TTR with vutrisiran and an improvement in death and cardiovascular events, as well as delays in disease progression, with vutrisiran as compared to placebo, with consistent effects across all pre-specified subgroups,” said Pushkal Garg, M.D., Chief Medical Officer, Alnylam. “We believe that, pending regulatory approval, vutrisiran has the potential to become a first-line therapy for ATTR amyloidosis with cardiomyopathy. We look forward to working with the FDA over the coming months on this application to bring this medicine to patients as rapidly as possible. Additional filings in other geographies are underway.”

The application to the FDA was based on positive results from HELIOS-B, a Phase 3, randomized, double-blind, placebo-controlled multicenter global study in patients with ATTR-CM with substantial background use of other effective therapies. The study demonstrated favorable effects of vutrisiran on outcomes of death and cardiovascular events, functional capacity and quality of life in patients with ATTR-CM. The safety profile of vutrisiran in HELIOS-B was consistent with the established profile of the drug. In HELIOS-B, rates of adverse events (AEs), serious AEs, severe AEs, and AEs leading to study drug discontinuation were similar between the vutrisiran and placebo arms.

Today, the Company will host its TTR Investor Day starting at 8:30 am ET in New York City. The event will feature presentations from the Company’s management team, including senior leaders from the commercial organization who will discuss launch preparation and highlight the potential for market leadership in ATTR-CM. The event will be webcast on the Investors section of the Company’s website, www.alnylam.com. A replay will be available on the Alnylam website within 48 hours after the event.

HELIOS-B Study Design

HELIOS-B (NCT: NCT04153149) was a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed and powered to evaluate the efficacy and safety of vutrisiran on the reduction of all-cause mortality and recurrent cardiovascular events as a primary composite endpoint in patients with ATTR amyloidosis with cardiomyopathy. The study randomized 655 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy. Patients were randomized 1:1 to receive vutrisiran 25mg or placebo subcutaneously once every three months during a double-blind treatment period of up to 36 months. After the double-blind period, all eligible patients remaining on the study to were able receive vutrisiran in an open-label extension period of HELIOS-B.

AMVUTTRA® (vutrisiran) U.S. Indication and Important Safety Information

Indication

AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

Important Safety Information

Reduced Serum Vitamin A Levels and Recommended Supplementation

AMVUTTRA® (vutrisiran) 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 AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A 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 AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).

For additional information about AMVUTTRA, please see the full Prescribing Information.

About AMVUTTRA® (vutrisiran)

AMVUTTRA® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of mutant and wild-type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, AMVUTTRA is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), which encompasses both wild-type and hereditary forms of the disease. For more information about AMVUTTRA, including the full U.S. Prescribing Information, visit AMVUTTRA.com.

About ATTR

Transthyretin amyloidosis (ATTR) 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 – hereditary ATTR (hATTR), which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant and impacts an estimated 200,000-300,000 people worldwide.1-4

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.5 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.6 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.5 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 in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. 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, Alnylam’s expectations regarding the safety and efficacy of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy; the potential for vutrisiran to obtain regulatory approval for the treatment of ATTR amyloidosis with cardiomyopathy; the safety and efficacy of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy, the potential of vutrisiran to including its potential to become a first-line therapy and a market-leading therapy for patients with ATTR amyloidosis with cardiomyopathy,; and Alnylam’s view with respect to the timing of regulatory review potential for a reduced review timeline by the FDA and any resulting approval(s) of vutrisiran for the treatment of ATTR amyloidosis in the U.S. and other countries Alnylam’s global regulatory submissions for vutrisiran 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, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its “Alnylam P5x25” strategy; Alnylam’s ability to successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates, including vutrisiran; actions or advice of regulatory agencies and Alnylam’s ability to obtain regulatory approval for its product candidates, including vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; and any delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2023 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.

1

Hawkins PN, Ando Y, Dispenzeri A, et al. Ann Med. 2015;47(8):625-638.

2

Gertz MA. Am J Manag Care. 2017;23(7):S107-S112.

3

Conceicao I, Gonzalez-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21:5-9.

4

Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.

5

Elbashir SM, Harborth J, Lendeckel W, et al. Nature. 2001;411(6836):494-498.

6

Zamore P. Cell. 2006;127(5):1083-1086.

 

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Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom (Investors and Media) [phone]

Josh Brodsky (Investors) [phone]