Using oral KVD900 as an on-demand treatment for hereditary angioedema (HAE) attacks is safe and significantly reduces both the use of rescue medications and the time to symptom relief, according to top-line results of a recently completed Phase 2 trial.
Notably, the oral therapy significantly speeded up the time it took to ease patients’ symptoms — to less than two hours, as compared with about nine hours.
Such results are similar to those now achieved by injectable treatments, the researchers said.
“We are very excited to share this positive data which shows that KVD900 is the first oral therapy to achieve clinical efficacy results comparable to current injectable therapies, while also demonstrating a promising safety and tolerability profile,” Andrew Crockett, CEO of KalVista Pharmaceuticals, the medication’s developer, said in a press release.
People with HAE who lack a functional C1-inhibitor (C1-INH) protein overproduce the enzyme kallikrein, which results in an increase in bradykinin, an inflammatory mediator that causes blood vessels to dilate and tissue to swell.
KVD900 is a small molecule inhibitor that treats acute swelling attacks by blocking the activity of kallikrein, thereby reducing levels of bradykinin. As an oral therapy, KVD900 addresses an unmet need among people with HAE, whose current on-demand treatment options are injectable.
The Phase 2 trial (NCT04208412) investigated KVD900 as an on-demand treatment in 53 adults with type 1 and type 2 HAE — subtypes caused by a deficiency in C1-IHN — who had experienced three attacks within the three months prior to enrollment.
The trial was conducted in two parts. In the first, all participants received a single 600 mg dose of KVD900 in an inpatient setting, designed to monitor the patients for safety and drug metabolism.
All patients then crossed over to a second part, in which they received either KVD900 or a placebo within an hour of the start of an attack. For a subsequent attack, the patients were switched over to either the medication or the placebo, the opposite of the treatment they had received earlier.
For this part of the trial, treatment was administered in an outpatient setting, and participants could take their conventional rescue medication, as needed.
Top-line results demonstrated that, within 12 hours of an attack, patients who used KVD900 as a treatment required rescue medications in 15% of cases, compared with 30% of placebo-treated attacks. The significant benefit of KVD900 persisted for 24 hours.
After that 12-hour period, the number of improved or stabilized attacks — as measured by a Patient Global Impression of Severity scale or rescue therapy use — also was significantly greater with KVD900 than with a placebo.
Notably, KVD900 significantly shortened the time it took for patients to experience some symptom relief, from a median of nine hours with a placebo to 1.6 hours.
No serious adverse side effects were reported and no participants withdrew from the trial due to side effects. During the first part, five individuals experienced a total of eight treatment-related adverse side effects. During the crossover portion, three patients experienced three treatment-related adverse side effects to treatment with KVD900, while two drug-related side effects occurred in two individuals after they were given the placebo.
KalVista also reported that KDV900 outperformed a placebo in the measurement of additional statistically significant exploratory endpoints.
The company plans to report the study’s full results at an upcoming medical meeting. Meanwhile, it has submitted a plan to the European Medicines Agency to initiate clinical studies in the EU of KDV900, also in children.
“The rapid onset of symptom relief and significant reduction in the use of rescue medication show that patients can confidently take KVD900 at the earliest signs of an attack and avoid the burden and discomfort of injections,” Crockett said.
“We look forward to working with regulatory agencies to bring the many advantages of KVD900 to patients as quickly as possible,” Crockett said.
KalVista also is developing KVD824, another inhibitor of the kallikrein protein, for the routine prevention of HAE swelling attacks. A study in healthy volunteers has shown a promising safety profile.
In the coming months, the company is planning to submit an investigational new drug (IND) application to regulatory authorities, requesting approval for a Phase 2 trial investigating KVD824 in HAE patients.
“We remain committed to advancing our oral HAE franchise, with submission of an IND this quarter for KVD824 as a prophylactic treatment and ongoing preclinical work on our oral Factor XIIa program,” Crockett concluded.
We are sorry that this post was not useful for you!
Let us improve this post!
Tell us how we can improve this post?