CinCor’s hypertension candidate flops a PhII test but plans to charge ahead with pivotal study
Toward the end of summer, Massachusetts-based CinCor Pharma was riding high with a $225 million raise, touting a positive data readout. But a closer look under the hood has revealed a few hiccups in its Phase II.
CinCor on Monday unveiled topline results from its Phase II trial, dubbed HALO, evaluating baxdrostat in patients with uncontrolled hypertension who are taking up to two blood pressure medications. The trial whiffed on its primary endpoint of evaluating change from the “baseline in mean seated” systolic blood pressure (SBP) in the intent-to-treat population in all dosage levels.
CinCor did try to salvage things by touting the safety of the candidate along with an analysis of non-Hispanic patients, which amounted to around 47% of the trial participants. Here, the biotech said around 81%-89% of the group had a reduction in SBP of 12.6 mmg, earning a p-value of p=0.001 in the high dose of 2 mg.
CinCor CMO Mason Freeman said in a statement:
While we still need to learn more about the factors driving different responses in our pre-specified sub-group analyses, it is clear that baxdrostat generated double-digit SBP reductions in study sub-groups, which include Black/African American patients, representative of approximately 81-89% of the hypertensive population of the US. The data also demonstrate a favorable safety profile and tolerability across the treated patient groups. Patients in HALO were not pre-selected for inclusion based on aldosterone, renin, or other hormonal characteristics, suggesting baxdrostat’s utility in the uncontrolled hypertensive population may be broader than expected.
CinCor is not looking to stop its work on baxdrostat, expecting the Phase III trials to still occur within the first half of next year. The program remains “on track” for a potential NDA submission in 2025. CinCor’s stock price $CINC has dropped around 43% since opening from around $26 a share down to under $15.
At least one analyst was left searching for answers from the data. Evercore’s Umer Raffat wrote to investors that “overall, this trial is impossible to interpret…not just the primary data, but also non-Hispanics [data].” He added there was a “really quite profound” placebo response that may have affected things.
“If we all agree that there is an odd pbo response in this trial, then we can also not trust the very basis of Cincor’s assertion that non-hispanics looked good,” Raffat wrote. “Said differently, if there are real trial conduct issues which makes it hard to interpret the trial, that same rationale applies to the 2 mg arm in non-hispanic subgroup as well.”
But while the biotech is facing a dip, some analysts are not throwing in the towel just yet. An analysis from Dennis Ding at Jefferies stated that while the HALO trial was missed and was not expected by Wall Street, the trials were not a core piece of the thesis.
“This could be perceived as a clearing event since investors were so nervous heading into HALO, and with the topline now behind us, investors could focus more on the path ahead including Phase III starting by mid-2023. Further, despite the negative topline, we’d argue the uncontrolled population was never going to be efficiently commercialized anyway nor core to the thesis and the blockbuster opportunity may still be intact in treatment-resistant patients,” Ding said.
Ding added that CinCor will meet with the FDA to discuss the upcoming Phase III, surmising that the biotech will run two separate Phase III trials and that it will be more “cautious and vigilant” on the design of the trial and may have more monitoring to reduce the effect of the placebo.
CinCor has gotten a lot of attention and funds over baxdrostat. In August, it garnered $225 million after touting initial Phase II data. And last year, the company scored a $143 million Series B round led by General Atlantic with a $100 million Nasdaq filing launching only a few weeks later.
CinCor’s Phase II also comes as it is facing stiff competition from other biotechs looking to get a hypertension drug into the market. Philadelphia-based Mineralys recently unveiled Phase II data for its aldosterone synthase inhibitor for treating hypertension and its associated cardiovascular diseases, which did reach its primary endpoint.