Alnylam Reports Positive Results from Phase 2 Study of Investigational Cemdisiran for the Treatment of IgA Nephropathy

-Treatment with Cemdisiran Resulted in a Higher Proportion of Patients Achieving Clinically Meaningful Reductions in 24-Hour Urine Protein to Creatinine Ratio, as Compared to Patients on Placebo -

- Consistent Proteinuria Reduction Seen with Secondary Endpoints -

- Cemdisiran Was Generally Well-Tolerated in Patients with IgA Nephropathy -

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) today announced positive results from a Phase 2 study of cemdisiran, an investigational RNAi therapeutic targeting the C5 component of the complement pathway, in development in collaboration with Regeneron Pharmaceuticals for the treatment of adult patients with immunoglobulin A nephropathy (IgAN). The results were presented at the 18^th European Meeting on Complement in Human Disease (EMCHD) being held in Bern, Switzerland on August 26-28.

“We are pleased to present additional data from our Phase 2 study demonstrating that cemdisiran had favorable effects on different measures of proteinuria – a strong risk factor for disease progression in patients with IgAN,” said Sonalee Agarwal, Ph.D., Vice President and Program Leader for the Cemdisiran program at Alnylam. “IgAN is an inflammatory disease that can lead to severe loss of kidney function. Thus, given the persistent unmet need in the treatment landscape of this progressive disease, we, together with our partners at Regeneron, are working expeditiously to advance this investigational RNAi therapeutic into Phase 3 clinical development.”

The data showed that at Week 32, as previously reported, cemdisiran demonstrated a clinically meaningful reduction in 24-hour urine protein to creatinine ratio (UPCR) – the primary endpoint of this Phase 2 study – with a 37 percent (90 percent CI: -0.5, 61) reduction in 24-hour UPCR observed relative to placebo. New results that were presented demonstrated an equivalent (36 percent [90 percent CI: -6, 62]) reduction in 24-hour urine total protein and a higher proportion, 32 versus 13 percent, of patients treated with cemdisiran as compared to those on placebo, respectively, achieving greater than or equal to 50 percent reduction in 24-hour UPCR. Spot urine data were consistent with 24-hour urine data, with the initial onset of treatment effect emerging as early as Week 8 and remaining stable over time. Specifically, patients on cemdisiran achieved a 46 percent (90 percent CI: 26, 60) placebo-adjusted reduction from baseline in spot UPCR at 32 weeks.

Furthermore, the results showed that cemdisiran was generally well tolerated in patients with IgAN with no adverse events (AEs) leading to treatment or study discontinuation during the double-blind treatment period. One death occurred in the cemdisiran arm due to cardiorespiratory collapse; this was not considered related to study drug by the study investigator. AEs reported by greater than or equal to 10 percent of patients in the cemdisiran arm were injection site reactions (41 percent) and peripheral edema (14 percent). There were no drug-related serious or severe AEs.

To view all results presented by Alnylam and collaborators at EMCHD please visit Capella.

About the Phase 2 Study

The Phase 2 trial is a randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of cemdisiran in adult patients with immunoglobulin A nephropathy (IgAN). Thirty-one adult patients (≥18 years and ≤ 65 years of age) with a clinical diagnosis of primary IgAN were randomized in a 2:1 cemdisiran to placebo ratio. The study was conducted in three periods. The first was an observational 14-week run-in period during which patients’ blood pressure, kidney function, degree of hematuria, and proteinuria were measured, and the standard of care remained unchanged. Patients did not receive study drug (cemdisiran or placebo) during this time. The second period was a 32-week treatment period, during which patients were dosed with 600 mg of cemdisiran or placebo every 4 weeks in combination with standard of care (angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB)). The third period is a 52-week open-label extension (OLE) period to further evaluate the long-term safety and clinical activity of cemdisiran. During the OLE, all patients (including those initially on placebo) are treated with cemdisiran in combination with standard of care. The primary endpoint of the study is the percent change from baseline in 24-hour urine protein to creatinine ratio at week 32. Secondary endpoints include additional measures of proteinuria, changes in hematuria, percent of patients with partial clinical remission, and frequency of adverse events.

About Immunoglobulin A Nephropathy

Globally, IgAN is the most common inflammatory disease affecting the glomerulus of the kidney often progressing to kidney failure. IgAN impacts approximately 2.5 out of 100,000 individuals per year, with a peak incidence in the third and fourth decades of life. Proteinuria, particularly > 1 g/day, is a strong risk factor for disease progression, with 20-40 percent of patients progressing to end-stage kidney disease (ESKD). While the exact cause of IgAN is incompletely understood, biochemical, genetic, and clinical data suggest IgAN is an autoimmune disease that may originate from overproduction of aberrantly modified immunoglobulins (otherwise known as antibodies) that results in the activation of the complement pathway and subsequent promotion of inflammatory mediators.

About Cemdisiran

Cemdisiran (ALN-CC5) is a subcutaneously administered, investigational RNAi therapeutic targeting the C5 component of the complement pathway. It is being developed in partnership with Regeneron Pharmaceuticals for the treatment of complement-mediated diseases. Cemdisiran utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc delivery platform.

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) 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 results of the Phase 2 study of cemdisiran in patients with IgAN, the potential timing to initiate a Phase 3 study, Regeneron’s involvement in the research, development and commercialization of cemdisiran, 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 recent 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; the pre-clinical and clinical results for its product candidates, including cemdisiran; 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 current 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220829005243/en/