Cretostimogene Grenadenorepvec

CG Oncology says its immunotherapy candidate that could help patients avoid surgery may deliver lasting responses in a certain form of bladder cancer based on late-stage trial data. The California biotech’s oncolytic virus therapy, named cretostimogene grenadenorepvec, has not yet reached median duration of response in a Phase 3 study in people with high-risk non-muscle invasive bladder cancer (NMIBC) who are unresponsive to the Bacillus Calmette-Guérin vaccine, which is usually part of a first-line regimen. That said, the median DOR exceeded 27 months at the Sept. 30 data cutoff, according to data presented Thursday at the Society of Urologic Oncology annual meeting in Dallas. For context, Merck’s Keytruda, which is often used in the second line, has a median DOR of around 16 months, CG Oncology CEO Arthur Kuan told Endpoints News in an interview. CG also reported that 97.3% of patients did not progress to muscle-invasive disease at 12 months. Also, just over half of the enrolled patients remained responsive to treatment at 24 months or more based on Kaplan-Meier estimations. Thursday’s durability data add to an interim readout in May that showed the asset cleared tumors in 75% of the 112 patients in the trial. The latest safety results were also consistent with the May data, with no reports of grade 3 or higher adverse events or treatment-related discontinuation. The most common side effects included bladder spasm, frequent urination and urgent urination. Cretostimogene “basically spares normal cells” because they don’t harbor RB/E2F1 mutations, Kuan said. Cretostimogene has the potential to become a “backbone bladder-sparing therapeutic” if it secures US approval, CG’s chief operating officer Ambaw Bellete said in a company release. Most patients in the Phase 3 did not have surgery to remove all or part of their bladder before joining the study. The biotech plans to file the treatment with the FDA in the second half of 2025. CG went public via a $380 million upsized listing on the Nasdaq in January. The company plans to launch cretostimogene alone in most markets, although it has a partnership with Kissei Pharmaceutical for Japan, South Korea, Taiwan and a number of other Asian countries except China. It had $540.7 million in cash and equivalents at the end of September, which should support it through 2027. Elsewhere, the biotech is also testing the treatment in the Phase 3 PIVOT-006 trial in intermediate-risk NMIBC. Market competition for NMIBC is steadily growing after the FDA greenlit ImmunityBio’s Anktiva plus BCG for a subgroup of patients in April. Johnson & Johnson is advancing a drug-device combination that it calls the “pretzel” for people with high- and intermediate-risk NMIBC.

A small US and Canadian gene therapy biotech has released a look at data from its experimental bladder cancer treatment, hoping to enter a field that includes CG Oncology, ImmunityBio, Johnson & Johnson and UroGen. EnGene said Thursday that its non-viral gene therapy led to a complete response in 71% of 21 patients assessed so far in the key cohort of its Phase 2 LEGEND trial. It’s one of several drugmakers testing treatments for patients with Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer, or NMIBC. Known as detalimogene voraplasmid or EG-70, enGene’s therapy is delivered to the bladder using a catheter four times during a 12-week cycle, for up to four cycles. EnGene said the treatment was “generally well-tolerated” and that no patients stopped the study because of drug-related safety concerns. Most side effects were grade 1 or 2 in severity, with two cases — peripheral edema and urosepsis — reaching grade 3. The biotech expects to collect data on about another 80 patients from the pivotal cohort portion of the open-label study before requesting regulatory approval. But enGene said it plans to package the data into a biologics license application in the middle of 2026 — about one year later than originally projected when the company went public by way of a SPAC combination last November. “The original guidance was more of an estimate, not based on experience. Now that we have a number of sites up and going, we see the enrollment coming in, we feel pretty confident about our [new] guidance,” Ron Cooper, who took over as CEO this summer , said in an interview. Merck’s product BCG is the standard treatment for patients with certain forms of the cancer, but the treatment is in shortage and doesn’t help all patients. Merck has said it expects to finish constructing a new facility to make BCG in Durham, NC, by late 2026. ImmunityBio’s IL-15 agonist Anktiva secured FDA approval in certain patients with the cancer in April, about 11 months after originally being rejected . The drug was approved in combination with BCG, however, meaning it doesn’t assuage concerns about the standard-of-care’s ongoing supply constraints. J&J is also working on a so-called “ pretzel ” drug-device combo. And UroGen is looking to treat patients with certain forms of NMIBC with a decades-old chemotherapy delivered as a gel . Last month, it asked the FDA for approval. CG Oncology, meanwhile, reported interim data from its Phase 3 in May, showing that 75.2%, or 79 out of 105 patients, had a complete response at any time to its therapy called cretostimogene grenadenorepvec. In enGene’s Phase 2 pivotal cohort, the complete response rate was 71% at any time, but it fell to 67% at three months and 47% at six months. For comparison, the complete response rate in CG’s Phase 3 was 63.6% at six months , but in a Phase 2 study, that rate was 44% . As it progresses with the rest of the pivotal trial, enGene said it is making protocol amendments to “reflect what’s done in clinical practice,” according to chief medical officer Raj Pruthi, a urological oncologist who joined the company in April after working on bladder cancer at J&J. “One of the amendments we’ve made recently is involving re-resection of T1 tumors,” Pruthi said. Another adjustment, at three months, is allowing for resection and reinduction of therapy for patients who have recurrence. “That reinduction of therapy is something that’s very familiar to us as urologists from the standpoint of that’s what we have done for years with BCG. And other late-stage agents and even ones approved by the FDA have also employed this reinduction paradigm.” CG has said it expects more data by the end of this year and plans to package the results for an approval request to the FDA. The biotech’s immunotherapy deploys a virus to infect and dismantle tumor cells. It had the first and biggest biotech IPO $CGON of the year, reeling in $380 million in January .