Dive Brief:
- A drug prospect from Relay Therapeutics has shown signs in a mid-stage clinical trial that it may be able to treat a cluster of conditions associated with the development of abnormal blood vessels.
- In 20 people with these “vascular anomalies,” a 12-week regimen of Relay’s therapy, zovegalisib, was associated with a 60% response rate across all doses tested, the company said Tuesday. Nearly all patients experienced an improvement in symptoms, and responses were observed in people with different disease subtypes and “PIK3CA” mutations driving their condition.
- Investigators did have to dial back dosing in 23% of people getting one of the doses Relay will take into further testing. But the company also said no patients discontinued treatment, most common adverse events were “low-grade, manageable, and reversible” and the drug appeared safe enough to envision the kind of “chronic use” that’d be necessary for these conditions. Company shares climbed by about 10% in early Tuesday trading.
Dive Insight:
Drugs that target alterations to the PIK3CA gene are coveted in the biopharmaceutical industry because of their potential to treat a wide range of cancers. These mutations are associated with a constellation of different tumors, giving therapies that can effectively target and treat those malignancies the chance to become lucrative products.
But these medicines have shown promise elsewhere, too. A few years ago, a retrospective study sponsored by Novartis proved blocking PIK3CA with a drug could treat “PROS,” a group of conditions that cause abnormal tissue growth. That study yielded a regulatory approval for what’s known as Vijoice, opening up a market Relay — and others chasing it — now hope to tap.
Zovegalisib gets after its target differently than Vijoice, a distinction Relay hopes might provide safety advantages over Novartis’ medicine. Relay’s also testing it on people not only with PROS, but other vascular anomalies such as malformations of the lymphatic vessels or veins. Investor interest in these disorders has been building of late because of the apparent need for a better, targeted treatment, wrote Leerink Partners’ Andrew Berens.
Novartis’ drug missed the main objective of a confirmatory trial, and other drugs are used off-label. In a Monday note, Berens predicted Relay’s candidate — which is being assessed in breast cancer as well — could generate a total of $2.8 billion in peak annual sales in vascular anomalies alone.
Novartis’ therapy was associated with response rates — shrinking overgrowths by a specific threshold — of anywhere from 11% to 27% in testing. Experts Berens spoke with viewed numbers at or above 20% to 25% at 12 weeks as “supportive of an initial signal” for zovegalisib. Differentiation could make Relay’s drug an “investigational leader” against these conditions,” he wrote.
While early, Relay claims to have hit that mark. In an email to BioPharma Dive, a spokesperson pointed to 9% rates of adverse events judged to be at least “Grade 3,” or “severe,” in Relay’s trial, versus anywhere from 30% to 71% across all studies of Novartis’ treatment. Response rates of 43% and 100% at lower and higher doses of zovegalisib, as well as an apparent impact on symptoms, also suggest the drug “has the potential to have differentiated safety and efficacy,” the spokesperson wrote.
Relay will take that twice-daily higher dose, plus a once-daily dose that’s even higher, into additional testing. “Finding the right balance” between potency and safety will be important, the spokesperson noted, but the results show there’s “a clear therapeutic window” to work with.
In a new note on Tuesday, Berens called the results “superlative” and indicated they may lead investors to view vascular anomalies as zovegalisib’s “main value driver.”
Relay will share another data update by the end of the year, the spokesperson said.
