Shares of CinCor Pharma fell more than 50% in premarket trading Monday after its investigational blood pressure drug failed to meet the primary endpoint in a Phase II trial.
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Shares of CinCor Pharma fell more than 50% in premarket trading Monday after the company announced its investigational blood pressure drug, baxdrostat, failed to meet the primary endpoint in a Phase II trial.
Data from the HALO study showed baxdrostat did not meet the primary endpoint - change from baseline in seated blood pressure after eight weeks of treatment - in the intent-to-treat (ITT) population of patients with uncontrolled hypertension. These patients are already taking up to two blood pressure medications at the maximally tolerated doses.
Baxdrostat, a highly selective, oral small-molecule inhibitor of aldosterone synthase, did not demonstrate statistical significance in reducing seated systolic blood pressure from baseline, the company reported.
Despite missing the primary endpoint, the drug did show some efficacy in a subgroup of patients, CinCor noted. In the ITT population, a subgroup analysis of non-Hispanic patients, which made up about 47% of the study, saw a 12.6 mmHg reduction in seated systolic blood pressure after receiving the 2mg dose.
The HALO trial evaluated three active doses of baxdrostat: 0.5 mg, 1 mg and 2 mg, compared to placebo in 249 patients randomized across all four dosing cohorts. Patients on background antihypertensive therapy were to discontinue treatment with their medications after eight weeks.
Hispanic or Latino patients represented 53% of the ITT population of the study, while non-Hispanic patients represented 46%. The non-Hispanic population represents approximately 81-89% of the hypertensive population of the United States, CinCor noted. There are an estimated 30 to 35 million patients with uncontrolled hypertension in the U.S.
Baxdrostat continued to show a strong tolerability profile, the company reported. No HALO patient discontinued due to treatment-related adverse events.
In a conference call Monday, the company said it believes the Hispanic/Latino population subgroup was a “proxy for non-adherent patients.” CinCor noted that 20 of the 54 participants who completed the 2 mg dosing regimen were non-adherent based on their PK. All but one of those patients was in the Hispanic/Latino subgroup, the company disclosed in its presentation.
CinCor also noted that renin response differs in the Hispanic/Latino group.
Chief Medical Officer Mason Freeman, M.D., said the company still needs to learn more about the factors that drove the different responses in its subgroup analysis. However, based on the available data, he said baxdrostat generated double-digit seated blood pressure reductions in study sub-groups, which include African American patients.
Patients in the HALO trial were not pre-selected for inclusion on the basis of aldosterone, renin or other hormonal characteristics. This suggests baxdrostat’s utility in the uncontrolled hypertensive population may be broader than expected, Freeman added.
When combined with data from the BrigHtn study of treatment-resistant patients, Freeman said HALO provided “key insights needed to select patient populations and dosing of baxdrostat” which the company plans to propose to the FDA for a Phase III program.
Earlier this month, data from the Phase II BrigHtn study showing treatment with baxdrostat demonstrated clinically significant and dose-dependent reduction in blood pressure was published in the New England Journal of Medicine. The primary endpoint of this trial was the change in mean seated systolic blood pressure from randomization to trial end after 12 weeks of treatment.
The HALO study used the same three dose levels of baxdrostat as the BrigHtn study, Freeman noted Monday. CinCor intends to meet with the FDA to discuss its late-stage clinical plans and anticipates initiating a pivotal Phase III study in the first half of 2023, Chief Executive Officer Marc de Garidel said Monday. The company will continue to explore baxdrostat’s effects in the Hispanic/Latino population, de Garidel added. Baxdrostat’s clinical program remains on track for a potential NDA submission in 2025, he said.
While de Garidel expressed excitement about the understanding of baxdrostat in the HALO study, investors in CinCor were of an opposite mind. The stock rapidly fell in premarket trading and continues to fall after the opening bell. Shares were trading at $14.29 as of 10 am EST, down from Friday’s close of $26.53.
