The FDA approved Anktiva as the first treatment for one BCG-resistant form of bladder cancer

On October 14, the U.S. Food and Drug Administration announced that Anktiva (nogapendekin alfa inbakicept-pmln), used together with Bacillus Calmette-Guérin, is now approved for adults with BCG-unresponsive, high-grade papillary-only non-muscle invasive bladder cancer. The agency called it the first FDA-approved treatment specifically for that group of patients.

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The decision extends a drug that was already on the market for a related form of the disease, and it rests on evidence gathered in that earlier population.

The papillary-only indication and Anktiva’s earlier approval

According to the FDA announcement, the new indication covers adults whose bladder cancer is high grade, papillary only, has not invaded the bladder muscle and has not responded to BCG. Altor BioScience, LLC is listed as the approval holder. Anktiva is given with BCG directly into the bladder through a catheter, once weekly for six weeks, with further treatment based on response, and treatment may last up to 37 months.

The product is not new to the market. In April 2024, Pharmaceutical Executive reported that the agency approved Anktiva with BCG for BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ, with or without papillary tumors, on the strength of a single-arm, multicenter trial of 77 evaluable patients. Pharmafile’s coverage of that decision added that the drug had received Breakthrough Therapy Designation and that approval rested on complete response rates and the duration of those responses, with the duration analysis still ongoing at the time. Patrick Soon-Shiong, executive chairman of ImmunityBio, described that approval as the launch of a next-generation immunotherapy beyond checkpoint inhibitors. Karim Chamie, a University of California, Los Angeles urologist and principal investigator of the study, called the long duration of complete response, ranging over 47 months, “a game changer for NMIBC patients.”

The 62% complete response and what it measures

The FDA did not run a separate trial for the papillary-only group. Instead the agency relied on the earlier carcinoma in situ approval together with clinical and laboratory evidence that the two forms share key features: they frequently occur together, they are difficult to tell apart under a microscope, and both carry a high risk of recurrence or progression after BCG fails. The supporting study, trial NCT03022825, enrolled 77 adults, some of whom also had papillary tumors.

In that study, 62% of patients achieved a complete response, meaning no high-grade cancer was detected on follow-up, according to the FDA. Of those responders, 58% maintained the response for at least 12 months and 40% for at least 24 months. Those durability numbers matter as much as the top-line rate, because a complete response is only useful to the extent that it lasts.

R. Angelo de Claro, director of the FDA’s Oncology Center of Excellence, said in the agency’s announcement that the FDA listens to patients, clinicians and researchers and acts when the science supports a new approach. The approach here is regulatory as much as clinical: using evidence from carcinoma in situ to support approval in a neighboring disease form, rather than requiring a fresh trial for each. The FDA’s reasoning is spelled out in its announcement: because carcinoma in situ and papillary-only disease are hard to distinguish microscopically and fail BCG in similar ways, evidence from one form was judged applicable to the other. Whether that logic extends to further bladder cancer subtypes was not addressed in the announcement, which is limited to the high-grade papillary-only population.

Side effects, surgery and regulatory follow-up

Common side effects and lab changes listed by the FDA include painful or frequent urination, urgency, blood in the urine, urinary tract infections, muscle or joint pain, chills, fever, and elevated blood creatinine and potassium. The prescribing information also warns that delaying surgery to remove all or part of the bladder can allow cancer to spread elsewhere in the body, which can be fatal. Treatment should stop if cancer persists after a second six-week course, returns or progresses, or side effects become unacceptable.

The surgery warning reflects where this patient group stands. The National Cancer Institute describes intravesical therapy such as BCG as treatment placed directly in the bladder to lower the chance of the cancer coming back, and says radical cystectomy, removal of the whole bladder, may be done when non-muscle-invasive bladder cancer involves a large part of the bladder. For patients whose cancer returns after BCG, the choice between another drug and a more extensive operation is the setting in which the new approval will be weighed, and the FDA’s own warning makes clear that postponing surgery carries risk.

The FDA also said it is working to finalize its draft guidance on developing drugs for BCG-unresponsive non-muscle invasive bladder cancer, issued in August 2024 as non-binding recommendations, and expects the final version to cover using carcinoma in situ study evidence to support approval for high-grade papillary-only disease. The guidance is non-binding and not for implementation until finalized, so the approval itself, not the draft, is what governs use of the drug today, and the FDA’s description of the drug’s side effects and surgery warning is the safety information attached to the announcement.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.