After facing an unexpected regulatory delay last month, KalVista Pharmaceuticals has leapt into the commercial realm with the FDA approval of its plasma kallikrein inhibitor sebetralstat.
The FDA has approved sebetralstat under the brand name Ekterly as a new, oral treatment option for acute attacks of hereditary angioedema (HAE) in adults and children ages 12 years and older, KalVista said in a July 7 press release. The nod came just a few short weeks after the agency missed its June 17 target date originally established for the decision.
At the time, KalVista blamed the delay on the “heavy workload and limited resources” at the agency, citing comments it had received from the FDA. The update fueled ongoing concerns from industry watchers that mass firings at the Department of Health and Human Services (HHS) and its constituent health agencies had hamstrung the FDA’s ability to keep its regulatory work on track.
Still, with the delay now behind the company, KalVista is pressing forward with plans to launch Ekterly in the U.S. “immediately," the company said in its release. Ekterly represents the small Massachusetts biotech’s first commercially approved product.
Ekterly’s green light marks a “defining moment for people living with HAE,” KalVista’s CEO, Ben Palleiko, said in a statement, stressing the drug’s ability to treat HAE attacks “the moment symptoms begin, wherever they are.”
HAE is a rare genetic disease that leads to deficiency or dysfunction in the C1 esterase inhibitor (C1INH) protein, KalVista explained in its approval announcement. The condition causes painful and debilitating attacks of tissue swelling at various points in the body, which can be life-threatening depending on the area affected, the company noted.
Prior to the approval of Ekterly, on-demand treatment for HAE attacks had to be administered via subcutaneous injection or intravenously, which can delay already time-sensitive intervention, the University of California, San Diego’s Marc Riedl, M.D., who served as an investigator on the pivotal trial that secured Ekterly’s approval, explained in KalVista’s release.
Though multiple drugs have already been cleared for HAE in the U.S.—both for acute attacks and prophylaxis—the simplified oral dosing of KalVista’s on-demand therapy has the potential to make Ekterly a “foundational treatment” for the disease, the company’s CEO Palleiko said.
The FDA gave Ekterly the thumbs up after reviewing data from KalVista’s phase 3 KONFIDENT trial, in which the drug demonstrated swifter symptom relief, reduction in attack severity and attack resolution versus placebo. The drug also appeared well-tolerated and had a safety profile on par with the dummy drug, KalVista said.
KalVista built on that body of evidence last fall with data from an open-label extension trial that found Ekterly helped patients treat HAE attacks within a median window of 10 minutes following attack onset. The latest data from that extension study, dubbed KONFIDENT-S, found that patients on Ekterly started experiencing symptom relief in a median of 1.3 hours for attacks involving the larynx or abdomen, and for breakthrough attacks in patients receiving long-term preventative treatment.
The FDA has struggled to meet several approval timeline targets this year and, in KalVista's case, the agency's Trump administration-appointed commissioner, Marty Makary, M.D., reportedly jockeyed for KalVista's drug to be rejected. Endpoints News reported about the agency's deliberations last month, citing internal communications at the regulator. An HHS spokesperson told the publication that the assertion Makary sought a Complete Response Letter for KalVista's drug was “totally false and untrue.”
Aside from KalVista, Novavax and GSK have also encountered delays at the regulator after their target decision dates came and went without approval verdicts. The FDA has subsequently approved both Novavax's and GSK's respective applications, which covered a protein-based COVID-19 vaccine and a new COPD indication for the antibody blockbuster Nucala.