Roche sees return on $310M investment with Alnylam’s Phase II hypertension win
Roche sees return on $310M investment with Alnylam’s Phase II hypertension win
Published: Sep 07, 2023
By Kate Goodwin
BioSpace
Alnylam Pharmaceuticals is already making progress on its July 2023 deal with Roche to co-develop and commercialize zilebesiran, the former’s investigational RNAi therapeutic. The Cambridge biotech reported positive topline Phase II results Thursday for its partnered gene-silencing therapy to treat hypertension.
In the KARDIA-1 trial, Alnylam’s zilebesiran met the primary endpoint of significantly reducing 24-hour mean systolic blood pressure (SBP) at three months for patients at high cardiovascular risk with hypertension. Zilebesiran helped lower patients’ blood pressure by more than 15 mmHg over placebo at the two highest doses tested. Key secondary endpoints for the trial were also met, according to Alnylam.
Most blood pressure drugs work by getting rid of excess water in the body to relax the blood vessels and make the heart pump with less force. Conversely, zilebesiran is a gene-silencing therapy that inhibits liver-expressed angiotensinogen (AGT), which plays a key role in the pathogenesis of hypertension. The RNAi therapeutic was associated with durable knockdown of serum AGT levels through month six.
The safety and tolerability profile were “encouraging,” according to Alnylam, with one death due to cardiopulmonary arrest that was considered unrelated to the drug. The adults enrolled in the study had untreated hypertension or who were on stable therapy with one or more medications.
A second Phase II study of the drug, KARDIA-2, is underway evaluating zilebesiran in combination with one of three standard antihypertensive agents. Topline results are anticipated in early 2024.
Cardiovascular disease remains the leading cause of death globally, with hypertension its most prevalent modifiable risk factor for premature cardiovascular death.
“Despite the availability of several classes of oral anti-hypertensive treatments, up to 80% of individuals globally remain uncontrolled, leaving them at an increased risk of cardiovascular, cerebrovascular and renal disease,” George L. Bakris, director of the American Heart Association Comprehensive Hypertension Center, said in a statement.
Roche inked a co-development and commercialization agreement with Alnylam for zilebesiran less than two months ago. Under the deal, Alnylam snagged $310 million upfront in cash with a potential $2.8 billion on the line in milestone payments. The two will share U.S. profits equally if the drug gets approved, while Roche holds the rights outside the country.
In January 2023, AstraZeneca scooped up cardiorenal disease biotech CinCor Pharma for its investigational hypertension treatment. A Phase II study of baxdrostat showed the drug was able to reduce SBP in patients with treatment-resistant hypertension by 11 mmHg over placebo. AstraZeneca is looking to combine the treatment with its blockbuster diabetes drug Farxiga.
Source: BioSpace
