Alnylam Completes Enrollment of HELIOS-A Phase 3 Study of Vutrisiran for the Treatment of hATTR Amyloidosis with Polyneuropathy

“We are pleased to have reached another important milestone for our TTR program by completing enrollment of the HELIOS-A study,” said Rena Denoncourt, Program Leader, Vutrisiran Program at Alnylam. “We are committed to developing multiple therapeutic options for this progressive, life-threatening and multisystem disease, and believe that vutrisiran, as a low-dose, once-quarterly, subcutaneously administered investigational therapeutic, can be an attractive option for patients. We look forward to sharing topline results in early 2021.”

HELIOS-A is a Phase 3 global, randomized, open-label study to evaluate the efficacy and safety of vutrisiran in patients with hATTR amyloidosis with polyneuropathy. The trial randomized patients 3:1 to receive either 25mg of vutrisiran subcutaneously once every 12 weeks or 0.3 mg/kg of patisiran intravenously once every three weeks. For most endpoints, results from the vutrisiran arm will be compared to results from the placebo arm of the landmark APOLLO Phase 3 study, which evaluated the efficacy and safety of patisiran in people with hATTR amyloidosis with polyneuropathy. The co-primary endpoints of HELIOS-A are the change from baseline in the modified Neurologic Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) score, at 9 months. Secondary endpoints include the change from baseline in key clinical evaluations including the timed 10-meter walk test (10-MWT), modified body mass index (mBMI), and Rasch-built Overall Disability Scale (R-ODS). The percent reduction in serum transthyretin (TTR) levels in the vutrisiran arm will be compared to the within-study patisiran arm. Additional exploratory endpoints will be assessed to determine the effect of vutrisiran on other aspects of the multisystem nature of this disease, including manifestations of cardiac amyloid involvement.

Vutrisiran has been granted Orphan Drug Designation in the United States and the European Union for the treatment of ATTR amyloidosis. The safety and efficacy of vutrisiran are also being evaluated in the ongoing HELIOS-B Phase 3 clinical trial in patients with ATTR amyloidosis with cardiomyopathy. The HELIOS-B study was initiated in late 2019 and is currently enrolling at sites around the world. Together, the HELIOS-A and -B studies comprise a comprehensive clinical development program intended to demonstrate the broad impact of vutrisiran across the multisystem manifestations of disease and the full spectrum of patients with ATTR amyloidosis.

About Vutrisiran
Vutrisiran is an investigational, subcutaneously-administered RNAi therapeutic in development for the treatment of ATTR amyloidosis, which encompasses both hereditary (hATTR) and wild-type (wtATTR) amyloidosis. It is designed to target and silence specific messenger RNA, blocking the production of wild-type and mutant transthyretin (TTR) protein before it is made. Quarterly administration of vutrisiran may help to reduce deposition and facilitate the clearance of TTR amyloid deposits in tissues and potentially restore function to these tissues. Vutrisiran utilizes Alnylam’s next-generation delivery platform known as the Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform. The safety and efficacy of vutrisiran have not been evaluated by the U.S. Food and Drug Administration, European Medicines Agency or any other health authority.

About Transthyretin (ATTR) Amyloidosis
Transthyretin (ATTR) amyloidosis is a rare, progressively debilitating, and fatal disease caused by misfolded TTR proteins that accumulate as amyloid deposits in multiple tissues including the nerves, heart and gastrointestinal (GI) tract. There are two types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis and wild-type (wtATTR) amyloidosis. hATTR amyloidosis is an inherited disease resulting in intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy. It is estimated to affect 50,000 people worldwide. The condition can have a debilitating impact on a patient’s life and may lead to premature death within 4.7 years of diagnosis. wtATTR amyloidosis is a nonhereditary, progressive type of the disease with undefined etiology. It affects an estimated 200,000-300,000 people worldwide. It primarily manifests as cardiomyopathy, which leads to heart failure and mortality within 2 to 6 years.

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 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
Alnylam (Nasdaq: ALNY) is leading 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 genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam’s commercial RNAi therapeutic products are ONPATTRO^® (patisiran), approved in the U.S., EU, Canada, Japan, and Switzerland, and GIVLAARI^® (givosiran), approved in the U.S. Alnylam has a deep pipeline of investigational medicines, including five product candidates that are in late-stage development. Alnylam is executing on its “Alnylam 2020" strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines to address the needs of patients who have limited or inadequate treatment options. Alnylam employs over 1,300 people worldwide and 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 or on LinkedIn.

Alnylam Forward Looking Statements
Various statements in this release, including, without limitation, Alnylam’s views and plans with respect to the potential for RNAi therapeutics, including vutrisiran, its expectations with respect to the timing for reporting topline results from its HELIOS-A Phase 3 study, its commitment to developing multiple therapeutic options for the treatment of ATTR amyloidosis, the intended goals of the HELIOS-A and -B studies to demonstrate the broad impact of vutrisiran across the multisystem manifestations of disease and the full spectrum of patients with ATTR amyloidosis, and expectations regarding the continued execution on its “Alnylam 2020” guidance for the advancement and commercialization of RNAi therapeutics, 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: Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates, including vutrisiran; the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all; actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; intellectual property matters including potential patent litigation relating to its platform, products or product candidates; obtaining regulatory approval for its product candidates, including lumasiran, and maintaining regulatory approval and obtaining pricing and reimbursement for its products, including ONPATTRO and GIVLAARI; progress in continuing to establish a commercial and ex-United States infrastructure; successfully launching, marketing and selling its approved products globally, including ONPATTRO and GIVLAARI; Alnylam’s ability to successfully expand the indication for ONPATTRO in the future; competition from others using technology similar to Alnylam’s and others developing products for similar uses; Alnylam’s ability to manage its growth and operating expenses and achieve a self-sustainable financial profile in the future, obtain additional funding to support its business activities, and establish and maintain strategic business alliances and new business initiatives; Alnylam’s dependence on third parties, including Regeneron, for development, manufacture and distribution of certain products, including eye and CNS products, and Ironwood, for assistance with the education about and promotion of GIVLAARI; the outcome of litigation; the risk of government investigations; and unexpected expenditures, as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. 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.

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