Alnylam Pharmaceuticals

Last updated
Alnylam Pharmaceuticals, Inc.
Company type Public
Industry Pharmaceutical
Founded2002;22 years ago (2002)
Headquarters Cambridge, Massachusetts, U.S.
Key people
Yvonne Greenstreet (CEO)
RevenueIncrease2.svg US$219.75 million (2019)
Decrease2.svg US$74.91 million (2018) [1]
Number of employees
1,323 (2019) [2]
Website alnylam.com

Alnylam Pharmaceuticals, Inc. is an American biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics [3] for genetically defined diseases. The company was founded in 2002 and is headquartered in Cambridge, Massachusetts. [4] In 2016, Forbes included the company on its "100 Most Innovative Growth Companies" list. [5]

Contents

History

The company is a spin-off from the Max Planck Institute for Biophysical Chemistry. [6] In 2002, Alnylam was founded by scientists Phillip Sharp, Paul Schimmel, David Bartel, Thomas Tuschl, and Phillip Zamore, and by investors Christoph Westphal and John Kennedy Clarke; John Maraganore was the founding CEO. [5] [7] [8] The company was named after Alnilam, a star in Orion's belt. The spelling was modified to make it unique. [9] In 2003, the firm merged with the German pharmaceutical company, Ribopharma AG. The newly formed company also received $24.6 million in funding from private-equity firms. [10] [11] On February 27, 2004, Alnylam Pharmaceuticals filed for an IPO. [7] [12] The company raised $26 million and began trading as ALNY on the Nasdaq stock exchange. [13]

In 2005, the company partnered with Medtronic to develop drug-device combinations to treat neurodegenerative disorders, [14] and in 2006 with Biogen Idec to develop treatments of progressive multifocal leukoencephalopathy. [15] In 2007, it entered into a nonexclusive alliance with Hoffmann-La Roche, in which Alnylam received $331 million in exchange for access to its technology platform. [16] and also partnered with Ionis Pharmaceuticals to found the company Regulus Therapeutics, focused on microRNA therapeutics. [17]

In 2009, the company formed alliances with Cubist Pharmaceuticals and Kyowa Hakko Kirin to market a drug targeted at respiratory syncytial virus. [18] In 2010, it expanded its previous collaboration with Medtronic to include the CHDI Foundation in its Huntington's disease focused research. [19] In 2011, it partnered with GlaxoSmithKline to develop RNAi technology enhancing vaccine production. [20] [21] The company entered into a 10-year alliance with Monsanto in 2012, to develop biotech solutions for the farming industry by developing natural molecules for crop protection. [22] [23] [24] In 2012, it formed a partnership with Sanofi Genzyme to develop a treatment for transthyretin-mediated amyloidosis, a hereditary disease in Asia. [25] [ third-party source needed ] In February 2013, it formed a partnership with The Medicines Company to develop a drug to treat a genetic form of high cholesterol. [26]

In July 2013, during a Phase I trial Alnylam demonstrated statistically significant reduction of a protein called transthyretin, or TTR and demonstrated human efficacy with intravenous and subcutaneous modes of administration. [27] In 2014, Sanofi Genzyme acquired a 12 percent stake in Alnylam and increased its rights to several of the company's drugs for $700 million. In a separate transaction Alnylam announced that it had purchased Merck & Co.'s Sirna Therapeutics, for $25 million cash and $150 million in stock. [28] [29] In 2015, the company had $41 million in revenue and a market cap of $5.2 billion. [30]

In 2016, the company purchased land in Norton, Massachusetts to build a manufacturing facility. [31] [32]

In October 2016 the Phase III clinical trial of the company's lead product, revusiran, was halted due to increased deaths in the drug arm of the trial, and the company said it was terminating development of the compound. [33] [34]

In February 2020, Alnylam appointed former Sanofi CEO Olivier Brandicourt to its board of directors. [35] In 2021, it was announced that Maraganore would step down as CEO, to be succeeded by the company's chief operating officer, Yvonne Greenstreet, on January 1, 2022. [36]

In December 2021, Alnylam submitted a clinical trial authorisation (CTA) application to the Medicines and Healthcare Products Regulatory Agency in the United Kingdom to initiate a Phase 1 study of ALN-APP, an investigational RNAi therapeutic targeting amyloid precursor protein (APP) for the treatment of Alzheimer's disease and cerebral amyloid angiopathy. [37]

On December 22, 2021, Novartis announced that the US Food and Drug Administration (FDA) approved Leqvio (inclisiran), a small interfering RNA (siRNA) therapy to lower low-density lipoprotein cholesterol. Leqvio is indicated in the United States 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. The effect of Leqvio on cardiovascular morbidity and mortality is being explored in clinical trials currently underway. Novartis obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals. [38]

Alnylam still does not earn money, but writes losses. The losses ("GAAP Operating Loss") from Alnylam were around $650 million in the late 2020. Alnylam expects to achieve net profits financially in 2022 or 2023. [39]

In July 2023, Roche partnered with Alnylam Pharmaceuticals in a deal worth $2.8 billion for the development of a hypertension drug. [40]

Products

In 2016, Alnylam Pharmaceuticals had 18 potential treatments [41] in various development stages in genetic medicine, cardiometabolic disease and hepatic infectious disease.

In late 2016, the company's lead candidate in phase III studies was patisiran, a treatment targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR), in patients with the compromised nervous system condition of familial amyloidotic polyneuropathy (FAP). [33] In August 2018, with its commercial name Onpattro, patisiran received the U.S. regulatory approval to treat polyneuropathy in patients with hereditary ATTR amyloidosis. [42]

FDA on patisiran

In September 2023, the FDA raised doubts about the efficacy of patisiran for treating cardiomyopathy associated with transthyretin-mediated amyloidosis (ATTR-CM). The FDA's Cardiovascular and Renal Drugs Advisory Committee meeting is scheduled for September 13, 2023. Although the APOLLO-B study met key endpoints, the FDA questioned the clinical significance of the results particularly for patients not on background therapy with tafamidis. The FDA is seeking the committee's input on the clinical meaningfulness and patient populations for patisiran use potentially challenging Pfizer's tafamidis dominance in ATTR-CM treatment. A decision on Alnylam's application is expected by October 8, 2023. Patisiran was previously approved in 2018 for hereditary ATTR amyloidosis polyneuropathy, becoming the first RNA interference therapeutic approved by the FDA. [43]

Related Research Articles

<span class="mw-page-title-main">Amyloidosis</span> Metabolic disease involving abnormal deposited amyloid proteins

Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight loss, shortness of breath, palpitations, and feeling faint with standing. In AL amyloidosis, specific indicators can include enlargement of the tongue and periorbital purpura. In wild-type ATTR amyloidosis, non-cardiac symptoms include: bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, small fiber neuropathy, and autonomic dysfunction.

Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. The corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Synthélabo merged with Aventis and renamed to Sanofi-Aventis, which were each the product of several previous mergers. It changed its name back to Sanofi in May 2011. The company is a component of the Euro Stoxx 50 stock market index.

<span class="mw-page-title-main">Small interfering RNA</span> Biomolecule

Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20–24 base pairs in length, similar to miRNA, and operating within the RNA interference (RNAi) pathway. It interferes with the expression of specific genes with complementary nucleotide sequences by degrading mRNA after transcription, preventing translation.

Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-mRNA, direct steric blockage, and exon content modulation through splicing site binding on pre-mRNA. Several ASOs have been approved in the United States, the European Union, and elsewhere.

<span class="mw-page-title-main">Regeneron Pharmaceuticals</span> American biotechnology company

Regeneron Pharmaceuticals, Inc. is an American biotechnology company headquartered in Westchester County, New York. The company was founded in 1988. Originally focused on neurotrophic factors and their regenerative capabilities, giving rise to its name, the company then branched out into the study of both cytokine and tyrosine kinase receptors, which gave rise to their first product, which is a VEGF-trap.

<span class="mw-page-title-main">Familial amyloid polyneuropathy</span> Medical condition

Familial amyloid polyneuropathy, also called transthyretin-related hereditary amyloidosis, transthyretin amyloidosis abbreviated also as ATTR, or Corino de Andrade's disease, is an autosomal dominant neurodegenerative disease. It is a form of amyloidosis, and was first identified and described by Portuguese neurologist Mário Corino da Costa Andrade, in 1952. FAP is distinct from senile systemic amyloidosis (SSA), which is not inherited, and which was determined to be the primary cause of death for 70% of supercentenarians who have been autopsied. FAP can be ameliorated by liver transplantation.

<span class="mw-page-title-main">Quark Pharmaceuticals</span> Israeli pharmaceutical company

Quark Pharmaceuticals is a pharmaceutical company that develops RNA interference-based treatments for chronic and acute diseases.

The familial amyloid neuropathies are a rare group of autosomal dominant diseases wherein the autonomic nervous system and/or other nerves are compromised by protein aggregation and/or amyloid fibril formation.

Christoph Westphal is an American biomedical businessman.

<span class="mw-page-title-main">Tafamidis</span> Medication for transthyretin amyloidosis

Tafamidis, sold under the brand names Vyndaqel and Vyndamax, is a medication used to delay disease progression in adults with certain forms of transthyretin amyloidosis. It can be used to treat both hereditary forms, familial amyloid cardiomyopathy and familial amyloid polyneuropathy, as well as wild-type transthyretin amyloidosis, which formerly was called senile systemic amyloidosis. It works by stabilizing the quaternary structure of the protein transthyretin. In people with transthyretin amyloidosis, transthyretin falls apart and forms clumps called (amyloid) that harm tissues including nerves and the heart.

<span class="mw-page-title-main">Arbutus Biopharma</span> Canadian Bio Tech Company

Arbutus Biopharma Corporation is a publicly traded Canadian biopharmaceutical company with an expertise in liposomal drug delivery and RNA interference, and is developing drugs for hepatitis B infection.

Wild-type transthyretin amyloid (WTTA), also known as senile systemic amyloidosis (SSA), is a disease that typically affects the heart and tendons of elderly people. It is caused by the accumulation of a wild-type protein called transthyretin. This is in contrast to a related condition called transthyretin-related hereditary amyloidosis where a genetically mutated transthyretin protein tends to deposit much earlier than in WTTA due to abnormal conformation and bioprocessing. It belongs to a group of diseases called amyloidosis, chronic progressive conditions linked to abnormal deposition of normal or abnormal proteins, because these proteins are misshapen and cannot be properly degraded and eliminated by the cell metabolism.

<span class="mw-page-title-main">Ionis Pharmaceuticals</span> Biotechnology company

Ionis Pharmaceuticals, Inc. is a biotechnology company based in Carlsbad, California, that specializes in discovering and developing RNA-targeted therapeutics. The company has 3 commercially approved medicines: Spinraza (Nusinersen), Tegsedi (Inotersen), and Waylivra (Volanesorsen) and has 4 drugs in pivotal studies: tominersen for Huntington’s disease, tofersen for SOD1-ALS, AKCEA-APO(a)-LRx for cardiovascular disease, and AKCEA-TTR-LRx for all forms of TTR amyloidosis.

Inclisiran, sold under the brand name Leqvio, is a medication used for the treatment of high low-density lipoprotein (LDL) cholesterol and for the treatment of people with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk-equivalents, and heterozygous familial hypercholesterolemia (HeFH). It is a small interfering RNA (siRNA) that acts as an inhibitor of a proprotein convertase, specifically, inhibiting translation of the protein PCSK9.

<span class="mw-page-title-main">Intellia Therapeutics</span> American biotechnology company

Intellia Therapeutics, Inc. is an American clinical-stage biotechnology company focused on developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. The company's in vivo programs use intravenously administered CRISPR as the therapy, in which the company's proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellia's ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases.

<span class="mw-page-title-main">Patisiran</span> Pharmaceutical drug

Patisiran, sold under the brand name Onpattro, is a medication used for the treatment of polyneuropathy in people with hereditary transthyretin-mediated amyloidosis, a fatal rare disease that is estimated to affect 50,000 people worldwide.

Michael James Polydefkis is an American neurologist. He is a Professor of Neurology at Johns Hopkins University School of Medicine and Co-Director of the Cutaneous Nerve Laboratory. Polydefkis research focuses on treating hATTR amyloidosis and diabetic and HIV-associated peripheral neuropathy.

John Maraganore is an American scientist, entrepreneur, and life sciences industry leader.

Vutrisiran, previously known as (ALN-TTRSC02), sold under the brand name Amvuttra, is a medication used for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. It is a double stranded small interfering RNA (siRNA) that interferes with the expression of the transthyretin (TTR) gene. Transthyretin is a serum protein made in the liver whose major function is transport of vitamin A and thyroxine. Rare mutations in the transthyretin gene result in accumulation of large amyloid deposits of misfolded transthyretin molecules most prominently in peripheral nerves and the heart. Patients with hATTR typically present with polyneuropathy or autonomic dysfunction followed by cardiomyopathy which, if untreated, is fatal within 5 to 10 years.

Eplontersen, sold under the brand name Wainua, is a medication used for the treatment of transthyretin-mediated amyloidosis. It is a transthyretin-directed antisense oligonucleotide. It was developed to treat hereditary transthyretin amyloidosis by Ionis Pharmaceuticals and AstraZeneca.

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