Trial sets up filing for enGene bladder cancer gene therapy
enGene's president and chief executive, Ron Cooper.
A phase 2 trial of enGene's detalimogene voraplasmid in non-muscle invasive bladder cancer (NMIBC) has delivered a positive result, setting it on course for a filing with the FDA next year.
The LEGEND trial showed a 62% complete response (CR) rate with the non-viral gene therapy at six months in NMIBC patients who had not responded to standard BCG therapy and had carcinoma in situ, a high-grade form of the cancer confined to the bladder lining that has a high risk of disease recurrence and progression.
NMIBC accounts for more than 70% of new bladder cancer diagnoses, and around 10% of patients present with CIS.
The preliminary readout, which included data on 62 patients at three months and 37 at six months, showed consistent effects with a 56% CR rate at three months and 63% at any time, and suggests that detalimogene has the potential to become a first-line therapy for this form of bladder cancer, according to enGene.
The primary endpoint of the study – CR at any time – was amended recently to align more closely with American Urological Association (AUA) guidelines, added the company. Along with the clinical update, it announced that the study has completed a higher-than-anticipated patient enrolment of 125.
Detalimogene would not be the first gene therapy for NMIBC if approved by the FDA, as Switzerland's Ferring Pharmaceuticals got a green light in 2022 for Adstiladrin (nadofaragene firedenovec) in a similar high-risk NMIBC population.
It was joined last year by ImmunityBio's Anktiva (nogapendekin alfa inbakicep), and in September of this year by Johnson & Johnson's Inlexzo (TAR-200), an intravesical delivery system for chemotherapeutic drug gemcitabine. Meanwhile, other treatment options include MSD's PD-1 inhibitor Keytruda (pembrolizumab), which can be used in NMIBC patients with CIS who are ineligible for or have elected not to undergo surgery to remove the bladder.
enGene reckons ease of use and a good safety profile – with less than 1% of patients seeing dose interruptions due to side effects – could differentiate it in the marketplace.
"Based on the emerging clinical profile and detalimogene's differentiated ease of use, we continue to believe there is a substantial commercial opportunity for detalimogene if approved," said the company's president and chief executive, Ron Cooper.
