US FDA: Anktiva Expanded for High-Grade BCG-Unresponsive Papillary Bladder Cancer

• The FDA has expanded Anktiva's approval for BCG-unresponsive, high-grade papillary-only bladder cancer, marking the first specific treatment for this condition.
• This approval represents a new FDA strategy, leveraging scientific similarities between carcinoma in situ (CIS) and papillary tumors to expand indications.
• The decision was supported by efficacy data from the NCT03022825 trial for CIS, which showed a 62% complete response rate.
• Anktiva, given with BCG, is administered directly into the bladder via catheter, with treatment potentially lasting up to 37 months.
• The FDA is finalizing guidance on developing drugs for BCG-unresponsive NMIBC, which will include using CIS study evidence for papillary-only NMIBC approvals.

This strategic shift in the FDA oncology drug approval strategy could accelerate the availability of new treatments for challenging cancer populations.

The U.S. Food and Drug Administration (FDA) recently expanded the approved use of Anktiva (nogapendekin alfa inbakicept-pmln), in combination with Bacillus Calmette-Guérin (BCG), to include adult patients diagnosed with high-grade papillary-only bladder cancer that has not invaded the bladder muscle and has shown no response to prior BCG treatment. This marks a significant milestone as Anktiva is the first FDA-approved therapeutic specifically targeting patients with this form of BCG-unresponsive, high-grade papillary-only disease. This regulatory decision also signals an evolving FDA oncology drug approval strategy for evaluating treatments for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).

This expanded approval builds upon the existing authorization for Anktiva in adults with carcinoma in situ (CIS), another type of NMIBC, whether or not papillary tumors were also present. The agency's determination was informed by the scientific similarities identified between CIS and high-grade papillary-only disease, allowing for a novel approach to extending treatment options. R. Angelo de Claro, M.D., Director of the FDA’s Oncology Center of Excellence, highlighted that the review of these cancer similarities enabled the agency to leverage existing results from CIS patients to broaden treatment access for individuals solely presenting with high-grade papillary tumors, potentially guiding future bladder cancer drug development efforts.

The FDA's decision to expand Anktiva's indication was rooted in a careful assessment of clinical and laboratory evidence demonstrating shared characteristics between carcinoma in situ (CIS) and high-grade papillary tumors. These two forms of non-muscle invasive bladder cancer (NMIBC) frequently coexist, can be challenging to differentiate microscopically, and carry a substantial risk of recurrence or progression when initial BCG therapy proves ineffective. This scientific congruence allowed the agency to apply the efficacy data from Anktiva's initial approval for CIS to the high-grade papillary-only patient population.

The initial approval for Anktiva in CIS patients was supported by the NCT03022825 clinical trial, which enrolled 77 adult participants, some of whom also presented with papillary tumors. The trial results showed that 62% of these patients achieved a complete response, meaning no high-grade cancer was detected during follow-up. Furthermore, among those who achieved a complete response, 58% maintained this response for at least 12 months, and 40% sustained it for a minimum of 24 months. These compelling outcomes, combined with the established scientific similarities, provided the foundation for the FDA's current expanded approval.

Non-muscle invasive bladder cancer (NMIBC) refers to bladder cancer that has not penetrated the muscle layer of the bladder wall. This category encompasses both carcinoma in situ (CIS), which manifests as flat patches along the bladder lining, and papillary tumors, which are small, finger-like growths extending from the lining into the bladder. While CIS is inherently high-grade, papillary tumors can be either low-grade or high-grade, with high-grade cancers posing a greater risk of growth and spread. For high-risk NMIBC, Bacillus Calmette-Guérin (BCG) is a standard initial treatment, working by activating the immune system within the bladder to combat cancer cells. However, in some cases, the cancer may persist or return, leading to a BCG-unresponsive state.

Anktiva, administered in conjunction with BCG, offers an additional mechanism to stimulate the immune system against cancer. The combination therapy is delivered directly into the bladder via a catheter, typically once a week for six weeks. Subsequent treatment is tailored to the patient's response and may continue for up to 37 months. Treatment should be discontinued if the cancer persists after a second six-week course, recurs, progresses, or if side effects become intolerable. Common adverse effects and laboratory abnormalities associated with Anktiva include painful or frequent urination, an urgent need to urinate, blood in the urine, urinary tract infections, muscle or joint pain, chills, fever, and elevated blood levels of creatinine and potassium.

This recent FDA approval of Anktiva for BCG-unresponsive papillary bladder cancer sets a significant precedent for pharmaceutical companies and their regulatory counsel. It demonstrates the U.S. Food and Drug Administration's willingness to leverage scientific commonalities between distinct, yet related, cancer types to broaden drug indications, potentially streamlining future approval pathways. This strategic shift in the FDA oncology drug approval strategy could accelerate the availability of new treatments for challenging cancer populations.

Further emphasizing this evolving approach, the FDA is actively working to finalize its draft guidance titled "Bacillus Calmette-Guérin-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment." This forthcoming bladder cancer drug development guidance is expected to provide detailed insights into how developers can utilize evidence from studies in patients with CIS to support approvals for treatments targeting BCG-unresponsive, high-grade papillary-only NMIBC. This development signals a clear direction for drug developers to consider broader applications for their oncology therapies based on shared biological characteristics, offering a more efficient route to market for critically needed treatments.

For pharmaceutical companies and their legal/regulatory counsel, this approval signals a new FDA precedent for leveraging scientific similarities between cancer types (CIS and high-grade papillary-only NMIBC) to expand drug indications. This approach, and the forthcoming FDA guidance on BCG-unresponsive NMIBC drug development, should be closely monitored as it could streamline future drug approval pathways for similar oncology treatments.

Source: Original reporting via FDA press release.