FDA Puts Hold on KalVista’s Phase 2 Trial of KVD824 for HAE Attacks

The U.S. Food and Drug Administration (FDA) has placed a hold on KalVista Pharmaceuticals’ proposed Phase 2 trial of KVD824 — which the developer had expected to launch by the end of June. 

The trial is intended to test KVD824 as a potential preventive treatment for hereditary angioedema (HAE) swelling attacks.

KalVista had submitted an investigational new drug application earlier this year, asking the FDA for permission to conduct the trial and assess the experimental oral tablet.

Now, in a response letter instituting the hold, the FDA requested that further analysis related to preclinical studies be made prior to the trial’s launch. The regulatory agency also wants refinements to the trial protocol. However, no new studies, nor new data were requested to support the study’s initiation, according to KalVista.

“We intend to fully comply with the requests and recommendations provided by the FDA,” Andrew Crockett, CEO of KalVista, said in a press release. “Although we no longer can confirm that the KVD824 Phase 2 trial will initiate this quarter, we are working to resolve their concerns in a timely fashion.”

The company also stated that the development of KVD900, its investigational oral on-demand treatment for HAE, will continue as planned. 

“Importantly, this letter relates solely to KVD824, and does not impact our activities or expectations with regard to KVD900, for which we continue to prepare for an end of Phase 2 FDA meeting and commencement of our Phase 3 efficacy trial,” Crockett said.

KVD824 is a blocker of the enzyme plasma kallikrein. Kallikrein increases the levels of bradykinin, an inflammatory molecule that causes blood vessels to widen and leak into the surrounding tissue, resulting in rapid bouts of swelling.

The therapy was first tested in a Phase 1 trial, in which participants received either a single dose of KVD824 — of up to 1,280 mg — or multiple doses of the therapy, up to 640 mg each. 

KalVista also conducted a formulation study involving 16 healthy individuals, which aimed to identify a preparation of the therapy that was both stable and acceptable to patients. In this study, therapy dose formulations ranging from 600 to 900 mg were given to participants twice daily, for 14 days. 

To date, a total of 121 people have received KVD824. In both studies, the rates of adverse events (side effects) were similar in those who received KVD824 as compared with a placebo. None of the participants withdrew, and no serious adverse events were reported.

Despite the clinical hold on the Phase 2 trial, KalVista ensured it will continue to work with the FDA on the development of KVD824, and will provide further updates as soon as possible.

The company also is planning to continue developing KVD900, its on-demand HAE therapy, which also blocks the activity of kallikrein. As an oral medication, KVD900 aims to replace the injectable on-demand treatments currently available.

KVD900 recently was tested in a Phase 2 trial (NCT04208412) in 53 adults with HAE who experienced three swelling attacks three months before entering the study. 

Top-line results showed that patients who received KVD900 within 12 hours of an attack needed rescue medications in 15% of the cases, while those given a placebo required rescue treatments in 30% of the cases. This benefit persisted for 24 hours. Moreover, the number of improved or stabilized attacks was significantly greater in KVD900-treated patients. 

Notably, the time it took for patients to report symptom relief was significantly shortened from nine hours with a placebo to 1.6 hours with KVD900. 

KalVista also is developing a new class of HAE oral therapies that block the Factor XIIa protein, which activates kallikrein. The company mentioned that several potent and highly selective Factor XIIa blockers that are able to enter the bloodstream when taken orally have already been identified.