KVD900 for HAE

KVD900 is an oral plasma kallikrein inhibitor and the most advanced compound in our portfolio of candidates for the treatment of hereditary angioedema (HAE). In February 2021, we reported positive results for a Phase 2 clinical trial demonstrating statistically and clinically significant responses for KVD900 as an oral on-demand treatment for HAE attacks.

Early treatment of HAE attacks has been shown to be key in maximizing treatment efficacy. Dosing with approved injectable treatments is often delayed undermining treatment outcomes. As a result of its straightforward oral administration combined with its rapid uptake and encouraging safety profile, KVD900 has the potential to offer HAE patients an effective and convenient treatment option.

The KVD900 Phase 2 was a randomized, double-blind, placebo-controlled, crossover clinical trial evaluating the efficacy and safety of KVD900 as an on-demand treatment for hereditary angioedema (HAE) attacks. The trial completed 53 adult HAE patients from 25 clinical sites in the United States and Europe. The trial included type 1 and type 2 HAE patients who had three attacks in 90 days prior to enrollment. During the first part of the two-part trial, patients received a single, open label 600 mg dose of KVD900 to evaluate pharmacokinetic and pharmacodynamic properties. All patients then entered part two of the trial, which was a double-blind investigation to assess the efficacy of KVD900 compared to placebo in a two‑attack, crossover design. During part two of the trial, patients took a single dose of 600 mg of KVD900 or placebo within one hour of the start of the first attack. The second attack was dosed with the alternative crossover treatment. Patients were able to use their conventional rescue treatment, as required.

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Topline Phase 2 Results

  • Attacks treated with KVD900 significantly reduced use of rescue (p=0.001), with 15% of KVD900 treated attacks rescued compared to 30% on placebo at 12 hours. This efficacy benefit of KVD900 was maintained at 24 hours (p=0.0005).

  • KVD900 significantly reduced time to onset of symptom relief (p=<0.0001) on a Patient Global Impression of Change scale (PGI-C), with a median time of 1.6 hours versus 9 hours for attacks treated with placebo.

  • KVD900 treated attacks achieved symptom relief more quickly than placebo treated attacks (p<0.0001) when assessed using a composite Visual Analogue Scale (VAS) score.

  • Within 12 hours of oral administration, KVD900 significantly increased the number of stabilized or improved attacks when assessed by a Patient Global Impression of Severity scale (PGI-S) or use of rescue (p<0.0001).

  • Additional exploratory endpoints were also statistically significant and favored KVD900 treatment over placebo.

  • There were no serious adverse events reported in the trial and no patients withdrew due to adverse events. In the open-label phase, 8 on-treatment drug-related treatment emergent adverse event (TEAE) were experienced by 5 patients. In the crossover phase of the trial, 3 on-treatment drug-related TEAEs were experienced by 3 patients (5.2%) following administration of KVD900, and 2 on-treatment drug-related TEAEs were experienced by 2 patients (3.6%) following administration of placebo.