KVD900 Slows HAE Attacks, Quickens Symptom Relief in Phase 2 Trial

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by Steve Bryson PhD |

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Single, on-demand treatment with the investigational oral medicine KVD900 safely and significantly slowed the progression of swelling attacks and shortened the time to symptom relief and resolution in adults with hereditary angioedema (HAE), according to the latest data from a Phase 2 trial.

“HAE patients continue to seek an oral option for on-demand treatment of their disease, to fully manage their disease or for breakthrough attacks for those on prophylaxis,” Emel Aygören-Pürsün, MD, the trial’s principal investigator, said in a press release.

“As KVD900 halted attack progression and resolved attacks more quickly in patients with HAE, while demonstrating a good safety and tolerability profile, it could be a valued choice for physicians and patients in managing HAE,” she added.

The study’s results were recently presented in a poster, titled “A single on-demand treatment with orally administered KVD900 significantly slows progression and accelerates resolution of attacks in patients with hereditary angioedema (HAE): Results of a phase 2, placebo-controlled, double-blind cross-over trial,” at the European Academy of Allergy and Clinical Immunology Congress, held July 10–12.

HAE is often caused by inherited mutations in the SERPING1 gene, which contains instructions for making C1-inhibitor (C1-INH), a protein that controls the activity of an enzyme called kallikrein. Low levels of C1-INH cause kallikrein to be overactive, which in turn leads to the excessive production of bradykinin — a pro-inflammatory molecule that stimulates the dilation and leakiness of blood vessels, resulting in swelling.

KVD900 is a small molecule designed to block kallikrein’s activity and lower bradykinin levels, potentially reducing swelling.

The recently completed Phase 2 trial (NCT04208412) enrolled 68 adults with type 1 or type 2 HAE who experienced more than three swelling attacks in the three months before enrollment.

The first part of the study focused on evaluating how KVD900 moved into, through, and out of the body when given at a single dose of 600 mg.

In the second phase of the study, patients treated two swelling attacks with KVD900 or a placebo in an outpatient setting at home. Participants were randomly assigned to take KVD900 or a placebo as a treatment for the first attack.

A total of 53 patients treated two swelling attacks, occurring in the arms and legs, abdomen, or genitals, or a combination of the arm, legs, and abdomen.

The trial’s main goal was to evaluate the effects of treatment on the proportion of attacks requiring the use of rescue medications. In line with top-line data previously reported, when participants received KVD900, 84.9% did not need rescue therapies after 12 hours. In contrast, 69.8% of patients treated with a placebo achieved the same outcome.

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On-demand KVD900 Speeds Symptom Relief, Reduces Use of Rescue Medicines

After 24 hours, 79.2% of patients who took KVD900 did not resort to rescue therapies. This was achieved by 60.4% of those given the placebo.

With KVD900, the proportion of attacks that did not require rescue medicines and did not cause symptoms to worsen — as measured by the five-point patient-reported Global Impression of Severity — was 79.2% after 12 hours and 69.8% after 24 hours. With a placebo, this outcome was achieved in 54.7% of the cases after 12 hours and 50.9% after 24 hours.

The seven-point patient-reported Global Impression of Change showed that 83.0% of patients treated with KVD900 rated their attacks as “a little better” after 12 hours compared with 50.9% of those on placebo, and after 24 hours, 84.9% of treated patients reported this rating compared with 64.2% of those on placebo.

The median time to feeling “a little better” or “better” was achieved after 1.6 hours with KVD900 versus nine hours with a placebo.

In addition to alleviating attack symptoms faster, KVD900 also accelerated attack resolution, with 56.6% of KVD900-treated patients ceasing to experience symptoms within 12 hours and 66.0% within 24 hours. With a placebo, 30.2% of patients fully recovered from the attack within 12 hours and 37.7% after 24 hours.

Nearly all adverse events were single occurrences that were mild or moderate, with no serious or severe events observed. As previously reported, three participants (5.2%) treated with KVD900 experienced adverse events within 48 hours of treatment during the second, placebo-controlled phase of the trial. These included upper abdominal pain, back pain, and headache.

In addition to data from this Phase 2 trial, KalVista Pharmaceuticals, the therapy’s developer, presented four other posters at the congress focused on assessing the prevalence and management of HAE in the U.S., as well as preclinical data from other treatment candidates.