In further evidence that Roche’s $310 million metabolic therapy bet will pay off, the Big Pharma’s Alnylam-partnered hypertension drug has notched up another phase 2 win.
The KARDIA-2 study enrolled 672 adults with mild to moderate hypertension who received either a 600-mg dose of the RNAi therapeutic zilebesiran or placebo on top of one of three approved hypertension meds—namely Pfizer’s Norvasc, Daiichi Sankyo’s Benicar or indapamide.
Patients who received zilebesiran added to one of these standard-of-care meds “experienced a clinically and statistically significant reduction in systolic blood pressure” when assessed by 24-hour ambulatory blood pressure monitoring at a three-month assessment, Roche said in a March 5 release.
Additional blood-pressure-related endpoints will be measured at the six-month mark, while safety is being assessed throughout the study. In a release, Alnylam said zilebesiran has so far demonstrated an “encouraging safety and tolerability profile” in the study.
While today’s announcement was light on any actual data, the companies said they expect to unveil the full results at a conference next month.
“We are thrilled that a single dose of zilebesiran achieved clinically significant, additional reductions in systolic blood pressure when administered to patients who are not adequately controlled with commonly prescribed antihypertensives,” Simon Fox, Ph.D., who leads Alnylam’s zilebesiran program, said in the company’s release.
“These KARDIA-2 results, showing durable additional levels of blood pressure reduction on top of what is achieved by standard of care first-line antihypertensives with an encouraging safety profile, reinforce our confidence in zilebesiran’s differentiated profile,” Fox added.
Zilebesiran is a subcutaneously administered RNAi therapeutic that targets liver-expressed angiotensinogen. This morning’s top-line results are another sign that Roche made the right call to secure the full ex-U.S. rights and co-U.S. rights to the candidate from Alnylam for $310 million upfront back in July 2023.
“With twice-yearly dosing in combination with standard of care medication, zilebesiran has strong potential to sustain lower blood pressure and reduce the risk of stroke, heart attack and death that can result from inadequate treatment,” Roche’s chief medical officer Levi Garraway, M.D., Ph.D., said in the Big Pharma’s release.
Should zilebesiran reach the market, Alnylam will be in line for up to $2.8 billion in milestone payments. Roche retains the option to spearhead the development of the drug for any future indications beyond hypertension.
The two companies used today’s readout to announce that they have kicked off a new phase 2 study, KARDIA-3, to assess zilebesiran as an add-on therapy in patients with high cardiovascular risk and uncontrolled hypertension despite treatment with between two and four approved antihypertensive meds.
Zilebesiran already sailed through the midstage KARDIA-1 study back in September 2023, where both 300-mg and 600-mg doses of the drug produced a more than 15-mmHg mean reduction in 24-hour systolic blood pressure after three months when compared to placebo.
William Blair analysts acknowledged that today's announcement was “light on details,” but said they were “encouraged by reports of another positive midstage study and look forward to additional data in the coming weeks.”
However, when it comes to Alnylam's long-term prospects, investors are more focused on vutrisiran, the analysts stressed. The phase 3 HELIOS-B trial of the RNAi treatment in hereditary transthyretin-mediated (hATTR) amyloidosis is expected to read out in June or July.