KalVista’s oral drug succeeds in pivotal hereditary angioedema study
13 Feb 2024
Phase 3Clinical ResultPhase 2
After weathering an earlier-stage clinical setback last year, KalVista Pharmaceuticals reported Tuesday that its more advanced hereditary angioedema (HAE) candidate sebetralstat succeeded in a Phase III trial as an on-demand treatment.
CEO Andrew Crockett said the company plans to submit the oral plasma kallikrein inhibitorplasma kallikrein inhibitor for FDA approval in the first half of 2024, with applications in Europe and Japan to follow later this year. "We believe [the KONFIDENT results] position sebetralstat to become the first oral, on-demand therapy for the treatment of HAE," he added.
Last October, KalVista was forced to terminate the Phase II KOMPLETE trial of another oral plasma kallikrein inhibitorplasma kallikrein inhibitor, called KVD824, after seven patients given the drug had experienced high liver enzyme increases.
While both KVD824 and sebetralstat belong to the same drug class, KalVista has described sebetralstat as a "distinct compound" with no treatment-related liver enzyme elevations seen in any clinical studies, including the Phase III KONFIDENT trial top-lined on Tuesday.
Quicker recovery from attacks
That study included adolescents, patients using long-term prophylaxis, and all attack severities. A total of 110 had treated at least 1 HAE attack. KalVista said the results, which will be shared in more detail at the American Academy of Allergy Asthma and Immunology (AAAAI) meeting later this month, showed that HAE attacks got better significantly faster when treated with either 300mg or 600mg of sebetralstat compared to placebo.
The median time to beginning of symptom relief was 1.61 hours with sebetralstat 300mg and 1.79 hours with the 600mg dose, whereas it was 6.72 hours with placebo. While not powered to statistically test treatment effect within subgroups, KalVista said the benefit was "consistent" across various demographic cohorts, including adolescents.
Sebetralstat also succeeded on secondary endpoints such as time to reduction in attack severity, which was 9.3 hours and 7.8 hours with the low and higher doses, respectively, versus over 12 hours with placebo. The proposition of patients achieving complete HAE attack resolution within 24 hours was also significantly greater with sebetralstat, where the rates were 44% and nearly 52% for the low and high doses, respectively, compared with just over 28% for placebo.
But shares down
Nevertheless, despite the positive readout sending company shares up roughly 39% in pre-trade on Tuesday, the stock was down 13% when the markets opened. That may be due to results showing that about 40% of patients given sebetralstat need a second dose, while close to 14% in the 300mg and 9% in the 600mg groups required conventional treatment within 12 hours.
That could put the drug at a disadvantage with a potential rival from Pharvaris, which is due to enter late-stage testing. Last month, the company said it would be moving its deucrictibant programme into Phase III as a prophylactic treatment for HAE attacks after the FDA lifted a clinical hold on the oral bradykinin B2-receptor antagonist.
Clean safety profile
Meanwhile, KalVista said is drug did not appear to raise any flags that had scuttled its KVD824 project. The company said sebetralstat had "a safety profile similar to placebo" in the KONFIDENT study, with no patient withdrawals due to any adverse event and no treatment-related serious adverse events. Treatment-related adverse event rates were 2.3% for sebetralstat 300mg, 2.2% for the 600mg dose, and 4.8% for placebo.
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