Regeneron and Alnylam Report Positive Interim Phase 1 Clinical Data on ALN-APP, an Investigational RNAi Therapeutic for Alzheimer’s Disease and Cerebral Amyloid Angiopathy
April 26, 2023 at 16:05 PM EDT
- Single Doses of ALN-APP Demonstrated Dose-Dependent, Rapid and Sustained Reduction of sAPPα and sAPPβ in Cerebrospinal Fluid, with Up to 90% at Highest Dose to Date -
- Encouraging Clinical Safety and Tolerability Profile Observed with Single Dosing to Date -
- Results Provide First Demonstration of Gene Silencing by RNAi Therapeutics in the Human Brain Using Alnylam's Proprietary C16 Platform -
TARRYTOWN, N.Y. and CAMBRIDGE, Mass., April 26, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) and Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) announced today positive interim results from the ongoing single ascending dose part of the Phase 1 study of ALN-APP, an investigational RNAi therapeutic targeting amyloid precursor protein (APP) in development for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy (CAA).
Twenty patients have been enrolled in three single-dose cohorts in Part A of the ongoing Phase 1 study in patients with early-onset Alzheimer’s disease. In this study to date, single doses of ALN-APP, which are administered by intrathecal injection, have been well tolerated. All adverse events were mild or moderate in severity, with available cerebrospinal fluid data for white blood cells and protein appearing similar to placebo. Early data for neurofilament light chain from a subset of cohorts (2 of 3 studied) looked comparable to placebo. Patients treated with ALN-APP experienced dose-dependent, rapid and sustained reduction in cerebrospinal fluid of both soluble APPα (sAPPα) and APPβ (sAPPβ), biomarkers of target engagement, with maximum reduction of 84% and 90%, respectively. Median decreases of both biomarkers of greater than 70% was sustained for at least three months at the highest dose tested. Detailed interim results from this study are planned to be reported at an upcoming scientific conference.
“ALN-APP, via its upstream targeting mechanism, has the potential to address the underlying cause of two devastating CNS diseases, Alzheimer’s disease and CAA, which affect many millions of people and their families around the world. Thus, we are excited by these interim clinical data for ALN-APP, which demonstrate rapid, substantial and sustained target protein reduction and encouraging safety and tolerability to date,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “We look forward to continuing to advance ALN-APP through the Phase 1 study, which will inform our future development plans in both Alzheimer’s disease and CAA.”
These early results establish the first human translation of Alnylam's proprietary C16-siRNA conjugate platform for central nervous system (CNS) delivery and are the first clinical demonstration of gene silencing in the human brain using an RNAi therapeutic.
“Establishing human proof of concept with ALN-APP is a major step in our efforts to expand our organic product engine to extrahepatic tissues like the CNS, a critical goal in our P5x25 strategy,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. “This further reinforces our belief that RNAi therapeutics have the potential to become a new class of medicines for silencing genes implicated in causing CNS diseases. Given these encouraging interim data, we are accelerating our efforts with Regeneron to bring forward additional genetically validated development candidates for other neurologic diseases, many of which have few or no therapeutic options for patients.”
“When we entered into this collaboration, the idea that you could profoundly silence disease-causing genes in the brain was simply a bold dream. The current data suggest that this dream is closer to becoming a reality, offering hope for the many patients suffering from incurable neurological diseases,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. “This approach to preventing production of amyloid precursor protein (APP) – as opposed to trying to clear amyloid plaques after they have already formed – provides a new way to potentially combat the scourge of Alzheimer’s disease, which has devastated so many families and proven historically difficult to treat.”
Further exploration of single-doses of ALN-APP is ongoing in Part A of the Phase 1 study (Canada, Netherlands, United Kingdom and United States) to evaluate longer term safety and duration of action and to identify the multi-dose regimen for Part B. Part B will include patients from Part A, and has received regulatory approval to proceed in Canada where the majority of the Part A clinical trial patients have been enrolled. Additional preclinical data, as well as the emerging clinical data announced today, will be shared with the FDA, which has placed a partial clinical hold on Part B in the U.S. due to findings observed in prior non-clinical chronic toxicology studies.
In addition to ALN-APP, Regeneron and Alnylam have named ten targets in the CNS as part of their exclusive collaboration established in 2019 to discover RNAi therapeutics for eye and CNS diseases.
About the Phase 1 Study of ALN-APP
The interim readout of the Phase 1 study of ALN-APP is focused on assessing safety, tolerability and levels of target engagement biomarkers, sAPP and sAPP.
About Alzheimer’s Disease
About Cerebral Amyloid Angiopathy
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
For more information, please visit www.Regeneron.com or follow @Regeneron on Twitter.
About Alnylam Pharmaceuticals
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Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website (https://newsroom.regeneron.com/) and its Twitter feed (https://twitter.com/regeneron).
Alnylam Forward Looking Statements
This press release discusses investigational RNAi therapeutics and is not intended to convey conclusions about efficacy or safety as to those investigational therapeutics. There is no guarantee that any investigational therapeutics will successfully complete clinical development or gain health authority approval.
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