Black man getting his blood pressure taken to check for hypertension, a sign of cardiovascular disease, with a blood pressure cuff
Credit: Linda Bartlett/National Cancer Institute, via Wikimedia

Roche will partner with Alnylam to develop the U.S. biotech’s RNA interference (i) candidate therapy zilebesiran for treatment of hypertension in a deal worth more than $310M.

Zilebesiran is an RNAi therapy designed to reduce blood pressure by inhibiting hepatic angiotensinogen synthesis. It is long acting and currently being tested in Phase II trials by Alnylam.

Roche will partner Alnylam and help get zilebesiran to the clinic and commercialize the therapy, assuming positive late-stage results.

As part of the deal, Alnylam will receive $310M as an upfront cash payment and will then be eligible for future development, regulatory and sales milestone payments, which could result in a total deal value of up to $2.8B. The biotech will also be entitled to an equal profit share of zilebesiran sales in the U.S., although Roche will have exclusive rights to commercialize the therapy elsewhere.

Results from a Phase I study of zilebesiran, recently pushed in the New England Journal of Medicine, show good results for the therapy. Side effects were mild, mostly injection site reactions, with no reported cases of hypotension, hyperkalemia, or worsening of renal function resulting in medical intervention.

After a single dose of 200 mg or greater, the participants had sustained reductions in blood pressure (more than 10 mmHg systolic and more than 5 mmHg diastolic) for up to six months.

Safety and efficacy of zilebesiran are now being assessed by Alnylam at Phase II either as a monotherapy (KARDIA-1) or in combination with one of three standard-of-care antihypertensive medications (KARDIA-2).

Alnylam are pioneers of RNAi therapies and the company has several approved therapies already on the market such as patisiran, approved in 2018 to treat polyneuropathy of hATTR amyloidosis. Most of the company’s products focus on rare diseases, but it has one approved cardiovascular disease product, inclisiran.

Inclisiran is used to lower cholesterol and global rights for this therapy are owned by Novartis, which took over rights from The Medicines Company in 2019. It is rapidly moving towards blockbuster status, which may be a motivation for Roche to invest in Alnylam’s new hypertension candidate therapy.

While there are plenty of antihypertensive drugs on the market, a long-lasting therapy with minimal side effects that only requires one dose every few months has significant attractions for patients.

“We are thrilled to announce this collaboration, as it combines Alnylam’s proven track record in RNAi therapeutics with Roche’s global commercial reach, commitment to innovation and desire to transform the landscape for patients with severe cardiovascular diseases,” said Yvonne Greenstreet CEO of Alnylam.

“With this collaboration, we now can develop zilebesiran in a more robust way, allowing us to have cardiovascular outcomes data in hand at launch to ensure results relevant not only for health authorities but also for access and clinical practice in order to ultimately reach as many patients as possible.”

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