Relay Reports Positive Results of Experimental Therapy for Rare Vascular Anomalies

Rare Daily Staff

Relay Therapeutics said Tuesday that early clinical data suggest its experimental drug zovegalisib may offer meaningful benefit for patients with rare, PIK3CA-driven vascular anomalies, with signs of both tumor reduction and symptom improvement.

The company reported results from the ongoing ReInspire trial showing that 60 percent of evaluable patients achieved a reduction in lesion volume at 12 weeks. At the lowest tested dose of 100 milligrams twice daily, 29 percent of patients had a volumetric response at the time of analysis, with updated data after the cutoff indicating a higher response rate. All patients in the study remained on treatment, and none discontinued due to adverse events.

Investigators also reported that 89 percent of patients showed clinical improvement at 12 weeks based on clinician assessments, while 79 percent reported improvement themselves. Measures of pain and other symptoms improved in a majority of patients, according to interim data presented at the International Society for the Study of Vascular Anomalies World Congress in Philadelphia.

“The combination of robust volumetric responses, symptomatic improvement, and a safety profile that supports chronic dosing underscores the potential of zovegalisib to meaningfully change the treatment paradigm for this underserved population,” said Don Bergstrom, president of research and development at Relay Therapeutics. “These early results strengthen our conviction in zovegalisib’s differentiated profile and its potential to deliver lasting benefit for patients and families affected by vascular anomalies.”

Vascular anomalies are a group of rare disorders caused by abnormal development of blood vessels, lymphatic vessels, and surrounding tissues. These conditions can lead to chronic pain, swelling, disfigurement, impaired mobility, and bleeding, and can significantly affect quality of life. A subset of these disorders is driven by mutations in the PIK3CA gene, including PIK3CA-related overgrowth spectrum, lymphatic malformations, and venous malformations.

Zovegalisib is an experimental small-molecule therapy designed to selectively inhibit mutant forms of PI3K alpha, a signaling protein frequently altered in both cancer and vascular anomalies. Unlike earlier PI3K inhibitors that target the active site and can affect both healthy and mutated forms of the protein, zovegalisib is engineered to bind allosterically, aiming to improve selectivity and reduce side effects. The drug is intended for chronic use and is being studied across a range of doses to identify an optimal balance between efficacy and tolerability.

The trial enrolled 32 patients ages 12 and older across three dosing groups. Among the 20 patients evaluable for response, 95 percent experienced some degree of lesion reduction, and responses were observed across multiple disease subtypes and mutation types. Patients previously treated with other therapies, including sirolimus and alpelisib, also showed similar response rates.

Safety findings indicated that adverse events were generally manageable and increased with dose. Among patients receiving lower doses, 23 percent required dose reductions, but no patients discontinued treatment. Severe treatment-related adverse events were reported in 9 percent of patients in these groups, and common side effects associated with earlier PI3K inhibitors appeared less frequent and less severe.

Higher doses, such as 400 milligrams twice daily, were deemed less suitable for this patient population and are not being prioritized for further development. The company has opened expansion cohorts at 400 milligrams once daily and 300 milligrams twice daily, while pediatric dose-finding studies are ongoing.

Relay Therapeutics said it will continue enrolling patients in the study and refining dosing strategies, while also advancing zovegalisib in late-stage trials for breast cancer.