Alnylam Comments on FDA Approval of Leqvio®, the First siRNA (RNAi Therapeutic) Approved to Reduce LDL-C

Rhea-AI Summary

Alnylam Pharmaceuticals announced the FDA's approval of Leqvio (inclisiran), the fourth RNAi therapeutic approved in the U.S., targeting LDL-C reduction in patients with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH). This therapy is the first RNAi treatment for high LDL-C, potentially benefiting up to 30 million Americans. The approval allows Alnylam to earn royalties on global sales by its partner Novartis, who holds commercialization rights.

Positive

• FDA approval of Leqvio opens access to a large market segment, with potential to significantly lower LDL-C levels.
• Leqvio can reduce LDL-C by up to 52%, making it a strong alternative for patients inadequately controlled by traditional treatments.
• Alnylam is set to receive royalties of 10-20% on global sales of Leqvio, enhancing revenue potential.

Negative

• Alnylam's royalty revenue from Leqvio will be split with Blackstone, impacting overall earnings.
• The effect of Leqvio on cardiovascular morbidity and mortality remains undetermined, raising questions about its long-term efficacy.

– Leqvio^® Becomes Fourth RNAi Therapeutic Approved by U.S. FDA and First and Only for Lowering LDL-C in Atherosclerotic Cardiovascular Disease (ASCVD) Which Can Affect Up to 30 Million Americans –

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today highlighted the significance of the U.S. Food and Drug Administration’s (FDA) approval of Leqvio^® (inclisiran), the fourth small interfering RNA (siRNA) therapy (or RNAi therapeutic) approved in the U.S., and the first and only to lower low-density lipoprotein cholesterol (also known as “bad cholesterol” or LDL-C). Leqvio is indicated in the U.S. as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. Alnylam scientists discovered inclisiran and published the first clinical data. Alnylam also supported early clinical development. As of January 2020, Novartis has obtained global rights to develop, manufacture and commercialize inclisiran under a license and collaboration agreement. Novartis AG continues to develop inclisiran and commercialize Leqvio worldwide, with Alnylam eligible to receive tiered royalties between 10 and 20 percent on global sales.

Leqvio is the fourth Alnylam-discovered medicine using its RNAi therapeutic platform to be approved to date. The Leqvio approval marks the first U.S. approval of an RNAi therapeutic indicated to treat a major risk factor for a highly prevalent disease. Alnylam launched its first RNAi therapeutic in 2018 with the FDA approval of ONPATTRO^® (patisiran) for treatment of the polyneuropathy caused by hATTR amyloidosis, a progressive and life-threatening, rare, genetic disease. Leqvio was approved to lower LDL cholesterol and has the potential to benefit millions of people with ASCVD and also those with HeFH around the world.

“The approval of Leqvio, a potentially transformational medicine for lowering LDL-C is a historic event for Alnylam and its RNAi therapeutics platform. The demonstrated ability of Leqvio to lower LDL cholesterol up to 52% versus placebo on top of maximally tolerated statins with just two doses per year after an initial dose and another at three months represents a breakthrough that carries the potential to treat millions of people with ASCVD who are struggling to control elevated LDL cholesterol,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “More broadly, we believe the approval of Leqvio validates the future potential of RNAi therapeutics in large population diseases, and facilitates Alnylam’s advancement toward its bold Alnylam P⁵x25 strategy and goals. We are proud to share in the significance of this milestone with Novartis who made this approval a reality.”

History of Leqvio (inclisiran)
Inclisiran was discovered by Alnylam and, in collaboration with The Medicines Company, advanced into clinical development in 2014. Upon successful completion of Phase 1 clinical studies, the ORION clinical program was launched in 2015. The FDA approval was based on results from the comprehensive Phase III ORION-9, -10 and -11 clinical trials, where all of the 3,457 participants with ASCVD or HeFH had elevated LDL-C while being on a maximally tolerated dose of statin therapy. This comprehensive Phase 3 program represents the largest clinical program conducted to date for an investigational RNAi therapeutic program. Two complementary Phase 3 cardiovascular outcomes trials, ORION-4 and the Novartis initiated VICTORION-2-PREVENT are currently ongoing.

“We believe that the creation of Leqvio was made possible by the development of our ESC-GalNAc conjugate delivery platform,” said Kevin Fitzgerald, Ph.D., Chief Scientific Officer of Alnylam, and scientist who led the initial development of Leqvio at Alnylam. “The U.S. approval of Leqvio will bring RNAi therapeutics to even more patients with elevated or inadequately controlled LDL-C. Moreover, this approval highlights the potential for additional Alnylam RNAi therapeutic programs in prevalent disease indications.”

In the U.S., Leqvio is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia HeFH or clinical ASCVD, who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality has not been determined.

The European Medicines Agency (EMA) granted inclisiran marketing authorization in December 2020 for adults with primary hypercholesterolaemia (heterozygous familial and non‑familial) or mixed dyslipidaemia, as an adjunct to diet in combination with a statin or statin with other lipid‑lowering therapies in patients unable to reach LDL‑C goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid‑lowering therapies in patients who are statin‑intolerant, or for whom a statin is contraindicated. Leqvio has now been approved in more than 50 countries.

As part of Alnylam’s strategic financing agreement with Blackstone, a leading private equity firm, 50 percent of Leqvio-related Alnylam royalties will flow to Blackstone.

About RNAi Therapeutics
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) 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), GIVLAARI^® (givosiran), and OXLUMO^® (lumasiran), as well as Leqvio^® (inclisiran), with Alnylam’s partner Novartis, which has obtained global rights to develop, manufacture and commercialize inclisiran under a license and collaboration agreement. Alnylam has a deep pipeline of investigational medicines, including six 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 expectations, plans, aspirations, and goals, including those related to the efficacy and safety profile of Leqvio and its potential to benefit millions of people with ASCVD and also those with HeFH around the world, the approval of Leqvio as a validation of the future potential of RNAi therapeutics in large population diseases which could facilitate the advancement toward its “Alnylam P⁵x25” strategy and goals, the potential for additional RNAi therapeutic programs in prevalent disease indications, and Alnylam’s aspiration to become a leading biotech company, 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 planned leadership transition at year end 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; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, 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 (and potentially vutrisiran, if approved) 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, 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211221005519/en/

Alnylam Pharmaceuticals, Inc.

Christine Regan Lindenboom

(Investors and Media)

617-682-4340

Josh Brodsky

(Investors)

617-551-8276

Source: Alnylam Pharmaceuticals, Inc.

FAQ

What is Leqvio and how does it work?

Leqvio (inclisiran) is an RNAi therapeutic approved by the FDA to lower LDL cholesterol in patients with ASCVD and HeFH, working by silencing mRNA associated with cholesterol production.

When was Leqvio approved by the FDA?

Leqvio received FDA approval on January 2020, marking it as the fourth RNAi therapeutic approved in the U.S.

What are the market implications of Leqvio's approval for Alnylam?

The approval of Leqvio allows Alnylam to earn tiered royalties that could significantly enhance its revenue, tapping into a large patient population.

What is the sales strategy for Leqvio following its FDA approval?

After FDA approval, Novartis is responsible for the global development, manufacture, and commercialization of Leqvio, while Alnylam receives royalties.

How many Americans could potentially benefit from Leqvio?

Leqvio has the potential to benefit up to 30 million Americans suffering from ASCVD or HeFH who require additional LDL-C lowering.