Alnylam lumasiran NDA granted priority review from FDA

The award of priority review status to the company’s New Drug Application for lumasiran adds to the previous grants of Breakthrough Therapy and Pediatric Rare Disease Designations. The FDA has set a PDUFA action date of 12/3/2020, and also indicated that they are not currently planning an advisory committee meeting as part of the NDA review. 

Additionally, the company’s Marketing Authorisation Application (MAA) for lumasiran has been submitted to and validated by the European Medicines Agency (EMA). Lumasiran was previously also granted an accelerated assessment by the EMA, which potentially reduces the agency’s evaluation time from 210 to 150 days. 

Lumasiran has also previously received Orphan Drug Designations for the treatment of PH1 in the U.S. and Europe, and has received a Priority Medicines (PRIME) designation from the EMA. 

Lumasiran is an investigational, subcutaneously administered RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) in development for the treatment of primary hyperoxaluria type 1 (PH1). HAO1 encodes glycolate oxidase (GO).Thus, by silencing HAO1 and depleting the GO enzyme, lumasiran inhibits production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1. Lumasiran utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables quarterly subcutaneous maintainence dosing with increased potency and durability and a wide therapeutic index.

Alnylam Reports Q1 2020 Financial Results and Business Updates

  • Net product revenues were $71.9 million in the first quarter 2020 representing 174 percent growth from the first quarter 2019 as a result of the addition of new patients on therapy and expansion into new markets for ONPATTRO, as well as the U.S. commercial launch of GIVLAARI.
  • Net revenues from collaborations were $27.5 million in the first quarter 2020, an increase from $7.0 million in the first quarter 2019, primarily due to revenues recognized from our Regeneron and Vir collaborations.
  • Cash, cash equivalents, marketable debt and equity securities, and restricted investments were $1.37 billion at the end of the first quarter 2020 compared to $1.55 billion at the end of 2019. The decrease was due to cash used in our operations to support overall growth. Cash at the end of the first quarter excludes $600.0 million in proceeds from the Blackstone strategic financing collaboration, which closed in the second quarter.
  • A $2 billion strategic financing collaboration with Blackstone is expected to enable Alnylam’s achievement of a self-sustainable financial profile without need for future equity financings. 
  • Full year 2020 financial guidance revised down slightly to reflect the effect of the-virus. Product revenues expected upto $300M, while GAAP and Non-GAAP expenses estimated upto $1.25B and $1.075B respectively.
  • Completed New Drug Application and Filed Marketing Authorisation Application for Lumasiran, Advancing Another Alnylam Investigational RNAi Therapeutic toward Market.
  • Announced New Positive Initial Topline Results from Ongoing Phase 1 Study of ALN-AGT in Hypertension with Over 90 Percent Knockdown of Angiotensinogen and an Over 10 mmHg Mean Reduction of 24-hour Systolic Blood Pressure Relative to Placebo.
  • Entered into a broad strategic financing collaboration with Blackstone under which Alnylam will receive up to $2 billion that is expected to enable Alnylam to achieve a self-sustainable financial profile without the need for future equity financing.
  • Expanded collaboration with Vir to include the development and commercialization of RNAi therapeutics targeting the-virus and up to three additional targets focused on host factors for the-virus, including angiotensin converting enzyme-2 (ACE2), transmembrane protease, serine 2 (TMPRSS2), and potentially a third host factor target to emerge from Vir’s functional genomics work.
  • Entered into an agreement with Dicerna to develop and commercialize investigational RNAi therapeutics for the treatment of alpha-1 antitrypsin (A1AT) deficiency-associated liver disease, and completed a non-exclusive cross-licensing agreement with Dicerna regarding the companies’ respective intellectual property for Alnylam’s lumasiran and Dicerna’s nedosiran investigational programs for the treatment of primary hyperoxaluria.
  • Appointed Dr. Olivier Brandicourt, former CEO of Sanofi, to the Company’s Board of Directors, and announced the retirement of Dr. Paul Schimmel, an Alnylam co-founder, in May 2020 after nearly 18 years of service; Dr. Schimmel will remain a member of the Company’s Scientific Advisory Board.

Vir and Alnylam identify RNAi therapeutic development candidate for the treatment of the-virus

Vir Biotechnology, Inc. () and Alnylam Pharmaceuticals, Inc. () today announced the selection of a development candidate for the potential treatment and/or prevention of redacted. […]
The companies plan to soon meet with the U.S. Food and Drug Administration (FDA) and other regulatory authorities to discuss a potential accelerated path for filing an Investigational New Drug (IND) or IND equivalent application at or around year-end 2020, less than a year since program initiation. The companies plan to advance -2703 (also referred to as ALN-COV), an investigational RNAi therapeutic targeting the redacted genome, as an inhalational formulation for the potential treatment and/or prevention of redacted.

In its discovery efforts, Alnylam synthesized over 350 small interfering RNAs (siRNAs) – the molecules that mediate RNAi – targeting highly conserved regions of the redacted genome, which were then analyzed bioinformatically and assessed in in vitro potency assays. Multiple highly potent siRNAs were identified that demonstrated a 3-log reduction of viral replication in an in vitro redacted live virus model conducted by Vir. In dose-response assays, -2703 was shown to have an effective concentration for 50% inhibition (EC50) of less than 100 picomolar and an EC95 of less than 1 nanomolar in the redacted live virus model measuring inhibition of infectious virion production. Further, -2703 has predicted reactivity against greater than 99.9 percent of the over 4300 redacted genomes currently available in public databases that meet analysis requirements, and is also predicted to have reactivity toward the redacted-CoV genome from the 2003 redacted outbreak. With this DC selection, Vir and Alnylam will work closely together to generate the data required to enable rapid commencement of clinical studies.

-2703 is an inhaled redacted-targeting siRNA that may have utility for prevention or for treatment. It leverages Alnylam Pharmaceuticals, Inc.’s latest advances in lung delivery of siRNAs and may have applicability to other redactedes as well. -2703 is the first development candidate selected in the company’s expanded collaboration with Alnylam for up to four RNAi potential therapeutics for redacted.

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.