UPDATED: KalVista sees a win in PhII for the rare genetic disorder HAE as it continues to chart a post-Merck course
Roughly a year after Merck walked away from a partnership with KalVista following a flop in diabetic macular edema, the biotech is back with data from another program it hopes can put it back on the map.
KalVista reported topline Phase II results for its lead candidate KVD900, an oral therapy meant to stem the effects of swelling attacks caused by the rare genetic disorder hereditary angioedema. In the 53-patient trial, the program hit statistical significance across all endpoints, reducing the need for individuals to use further treatment in subsequent attacks and alleviating symptoms more quickly than placebo.
News of the results sent KalVista $KALV shares soaring more than 115% in pre-market trading.
KVD900 itself is a plasma kallikrein inhibitor that KalVista hopes can become the first widely available pill for HAE. The disease manifests as unpredictable swelling in various body parts and can become life-threatening if an attack occurs in the airways.
There are lots of treatments out there for HAE, all of which are self-administered injections or IV infusions. Normally, patients living with the disease are able to feel an attack coming on, but not how severe the attack is or how long it will last. Because the swelling can occur randomly, individuals often carry around two different types of treatment to be extra sure they’ll have something to stop the attacks.
That can be quite cumbersome on a patient’s quality of life, however, KalVista CEO Andy Crockett told Endpoints News. These treatments typically require cold storage, and it can be difficult to find a private spot for patients to give themselves the injections. And the administration process itself is already a burden given that they’re racing against the clock to tamp down swelling.
With their oral pill, KalVista is banking on the added convenience and discretion such an option will afford patients.
“What we think with oral therapy is we have an opportunity to really bring a paradigm shift, which is to remove those barriers,” Crockett said. “It can enable that type of treatment early when the attack begins that hasn’t been enabled so far.”
The Phase II study was randomized and double-blinded, and separated into two parts. Individuals received a single, open-label dose in the first part, and then were randomized into the second part. The trial was designed to encompass two swelling attacks — patients took either KVD900 or placebo within an hour after the first attack, and then used their normal treatment regimen following the second. KalVista enrolled patients who’d had three attacks in the 90 days leading up to the trial.
In the primary, KVD900 significantly reduced use of such rescue treatments, with 15% of patients needing treatment after 12 hours in a second attack compared to 30% on placebo. And in a key secondary endpoint, the candidate significantly reduced time to onset of symptom relief on a patient-reported scale, with a median time of 1.6 hours against nine hours for placebo. Both figures hit pristine p-values, notching p=0.0010 and p<0.0001, respectively.
Despite the relative ease of such oral treatment, Crockett said many patients were concerned that pills might be less efficacious than their typical injectables. But he said Tuesday’s data should alleviate those worries as the results, paired with KVD900’s rapid onset in the Phase II study, shows it can compete with the best of the rest.
“Patients in HAE, they want oral therapy. But the injectable therapies they’ve had for a number of years provide really good efficacy,” Crockett said. “They don’t want to have to, if you will, trade efficacy for the benefit of oral therapy. That’s the promise we look to deliver on now.”
Analysts were also impressed by the data, with SVB Leerink’s Joseph Schwartz writing that the results exceeded even the most bullish expectations.
“We believe that results could potentially strengthen in a Ph.3 trial of KVD900, as patients will have more confidence in an investigational treatment making them less likely to reach for their rescue medicine,” Schwartz wrote to investors.
The next steps will involve meeting with the FDA to determine what a pivotal trial might look like. KalVista isn’t offering any timelines on when that meeting or the trial will occur, but Crockett said future studies will probably look similar to this Phase II.
Tuesday’s results come almost one year to the day after Merck dropped out of a partnership with KalVista, one that had promised up to $760 million for a diabetic macular edema drug. Both doses of the candidate whiffed on the Phase II primary, sending shares stumbling and Merck packing.
Since then, KalVista has focused primarily on HAE, with KVD900 at the forefront. The company is also working on a preventative treatment with their KVD824 program, which is expected to see an IND submission sometime this quarter.