KalVista Pharmaceuticals’ oral plasma kallikrein inhibitor has reduced the use of rescue medication in patients suffering swelling attacks associated with a rare disease. The phase 2 results boost KalVista’s prospects of establishing KVD900 as an alternative to injectable treatments such as Takeda’s Firazyr and Pharming’s Ruconest.
KVD900 is designed to bring fast relief during the severe swelling attacks experienced by people with hereditary angioedema (HAE). Currently, HAE patients use injectable treatments to counter the attacks, but KalVista wants to give them a more convenient oral option.
The phase 2 clinical trial enrolled 53 adult HAE patients who had experienced three attacks in the 90 days prior to recruitment. All patients received a single, open label 600-mg dose of KVD900 in the first stage of the study, before being randomized to get the drug or placebo in the second crossover stage. The second stage tracked patients until they had two attacks to compare KVD900 to placebo.
Fifteen percent of attacks treated with KVD900 required rescue medication in the 12 hours after onset, versus 30% of attacks in the placebo arm. The difference was statistically significant, causing the trial to hit its primary endpoint. The trial also linked KVD900 to reduced use of rescue medication at 24 hours.
Median time to symptom relief in patients on KVD900 was 1.6 hours. The figure compares favorably to the nine hours for placebo. More importantly, the time to symptom relief with KVD900 is in line with that for the injectable Ruconest, which typically takes 1.5 hours to ease the effects of an attack. Time to symptom relief was the primary endpoint in the phase 3 that supported Ruconest approval.
On a different symptom score, namely the composite Visual Analogue Scale (VAS), KVD900 provided symptom relief in a median of six hours, versus more than 12 hours for placebo. Takeda’s Firazyr won approval with a median time to onset of symptom relief of two hours on composite VAS, suggesting, with the usual caveats about the unreliability of cross-trial comparisons, that it may act faster.
KalVista compared the KVD900 and Firazyr VAS data in a presentation. In KalVista’s view, the data show early intervention with KVD900 leads to lower severity. KalVista sees the effect as a key benefit of oral therapy and consistent with modern HAE treatment recommendations.
Related treatment emergent adverse events were rare. No patient suffered a serious adverse event in the clinical trial, nor did anyone withdraw due to adverse events.
KalVista is now planning to hold an end of phase 2 meeting with the FDA before moving quickly into phase 3. Investors cheered the progress signified by the phase 2 readout, sending shares in KalVista up more than 200% in premarket trading.