KalVista's persistence with sebetralstat pays off with Konfident phase 3 victory

KalVista Pharmaceuticals pushed a great many of its clinical chips towards sebeltralstat, and, now, the bet appears to have paid off. The oral, fast-acting hereditary angioedema (HAE) treatment hastened the time to symptom relief, meeting all primary and key secondary endpoints in a phase 3 trial. 

The biotech reported Tuesday that both the 300-mg and 600-mg doses of sebeltralstat experienced quicker symptom relief by roughly four hours each compared to placebo, the primary endpoint of the trial. No patients withdrew from the phase 3 KONFIDENT study due to adverse events, and no treatment-related serious side effects were reported. 

“These data show that sebetralstat may provide a compelling treatment option for physicians and patients as an effective and safe oral treatment with rapid relief for HAE attacks,” CEO Andrew Crockett said in a release. 

In addition to the time to symptom relief, sebeltralstat was found to more quickly remedy attack severity compared to placebo. KalVista also reports that treated patients “demonstrated a significantly faster time to complete attack resolution” than those given placebo. 

HAE is a genetic disease marked by low levels or dysfunction of the C1 inhibitor. Patients can be struck with bouts of severe swelling across the body, and attacks can be fatal if they impact the lungs.

Ionis Pharmaceuticals is on the precipice of asking the FDA to approve its candidate after reporting that it reduced the rate of swelling attacks compared to placebo in a phase 3 trial. And one of the CRISPR-wielding biotechs, Intellia Therapeutics, is working on an option that would knock out a gene thought responsible for producing a problematic protein associated with HAE development. 

As for KalVista, the results validate the prioritization of sebeltralstat after a previous oral option, KVD824, failed to impress. The company scrapped further development of that med back in October 2022 after reporting elevated liver enzymes in some patients. Sebeltralstat was made the sole focus from that point on, with no additional clinical programs in the pipeline. The data tee up an approval application to regulators, with KalVista previously guiding that it would submit those data to the FDA in the first half of 2024. 

The question now is whether any commercialization partners will come calling as the biotech manages cash and early assets. KalVista reported having $103.2 million in cash and equivalents as of the end of October 2023, down from nearly $150 million at the same point in 2022. The company is continuing to progress a preclinical, oral factor IIXA inhibitor to treat HAE prophylaxis, though KalVista has yet to guide on when an investigational new drug application may be submitted.