Cemdisiran, an RNAi mono-therapeutic intended to treat IgAN is poised to enter Phase III clinical studies after positive Phase II topline results were shared Thursday morning.
Alnylam CEO Yvonne Greenstreet, Courtesy of Alnylam Pharmaceuticals
Alnylam Pharmaceuticals’ five-year strategy, “Alnylam P5x25,” is showing early signs of success just five months after it was first announced at the 2022 J.P. Morgan Health Care Conference.
Encompassed within this strategy is cemdisiran, an RNAi mono-therapeutic poised to enter Phase III clinical studies after positive Phase II topline results were shared Thursday morning.
Cemdisiran is a product of Alnylam’s Enhanced Stabilization Chemistry (ESC)-GaINAc delivery platform and was co-developed with pharma giant Regeneron. The investigational therapeutic is intended to treat patients with immunoglobulin A nephropathy (IgAN).
The Phase II study included 31 participants, divided 2:1 respectively amongst placebo and experimental groups. The experimental group receiving cemdisiran demonstrated an average 37% reduction in urine protein to creatinine ratio, relative to placebo, tracked over a 24-hour period. The change from baseline of the 24-hour urine protein to creatinine ratio is the primary endpoint of this study.
Sonalee Agarwal, Ph.D., vice president and leader of the cemdisiran program at Alnylam, commented on the topline results.
“We are encouraged by these topline results with cemdisiran demonstrating what we believe to be clinically meaningful reductions in proteinuria – an important prognostic factor in IgA nephropathy,” Agarwal said. “IgAN is the most common inflammatory disease affecting the glomerulus of the kidney. It can progress to end-stage kidney disease if left untreated. Given the limited treatment options and significant unmet need in IgAN, we, together with our partners at Regeneron, are formulating our plans for the Phase III clinical development of cemdisiran.”
Alnylam’s P5x25 strategy also features the development of several other investigational candidates. A few of these are expected to produce clinical data this year, including an RNAi therapeutic for Alzheimer’s Disease (AD), a candidate intended to treat Stargardt disease and a treatment for gout.
Yvonne Greenstreet, CEO of Alnylam, explained the five-year strategy as a roadmap for how the company will serve “at least half a million patients around the world, as well as bring forward more marketed medicines - six plus – and continue to build this rich clinical pipeline.”
As an investigational treatment for early-onset AD, ALN-APP will enter a Phase I clinical setting this year. The data from this trial is expected to be generated before 2023. Phase I study results are also expected to be shared later this year for Alnylam’s ALN-XDH, a potential treatment for gout.
Zilebesiran is the first RNAi therapeutic intended to treat a central nervous system disorder, AD. Positive Phase I study data for zilebesiran was shared in late 2021, with an update expected later this year. Participants in the trial demonstrated sustainable angiotensinogen and blood pressure levels for at least six months.
Vutrisiran, Alnylam’s multi-indicational candidate, is currently being developed as a treatment for Stargardt disease, a rare and hereditary illness presenting clinically as toxic levels of vitamin A accumulating in the patient’s retina and leading to blindness.
Plans for Phase III trials for vutrisiran indicated for Stargardt disease are expected to begin in late 2022. For the indication of ATTR amyloidosis, the U.S. Food and Drug Administration has scheduled a PDUFA review date in July.
