Recently, the U.S. Food and Drug Administration (FDA) expanded the approved indication for Anktiva (nogapendekin alfa inbakicept-pmln) in combination with Bacillus Calmette-Guérin (BCG) to include adult patients with high-grade, papillary-only bladder cancer whose cancer has not invaded the bladder muscle layer and who are BCG-unresponsive. Anktiva thus becomes the first FDA-approved therapy specifically for patients with BCG-unresponsive, high-grade papillary-only disease.
A New Review Approach
This approval marks a new approach by FDA in evaluating therapies for BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC). FDA's decision was based both on evidence previously supporting Anktiva's approval for another type of NMIBC (i.e., adult patients with carcinoma in situ (CIS), with or without papillary tumors) and on the scientific similarities between CIS and high-grade papillary-only disease.
Comments from a Medical Expert
R. Angelo de Claro, M.D., Director of FDA's Oncology Center of Excellence, said: "We listen to patients, clinicians, and researchers, and act when science supports a new path. For Anktiva, our review of the similarities among these cancer types allowed us to build on the findings in patients with CIS and expand treatment options for patients with only high-grade papillary tumors. This approach may also help guide the development of future therapies."
Understanding NMIBC: CIS and Papillary Tumors
NMIBC refers to bladder cancer that has not grown into the bladder muscle layer and can include two forms: CIS and papillary tumors. CIS forms flat patches along the inner lining of the bladder, while papillary tumors grow from the inner lining into the bladder cavity as small finger-like projections. CIS is always high-grade, whereas papillary tumors can be low-grade or high-grade. Compared with low-grade cancers, high-grade cancers are more likely to grow and spread.
Treatment for high-risk NMIBC usually begins with BCG, which activates the immune system in the bladder to fight cancer. However, sometimes the cancer persists or recurs. Combining Anktiva provides the immune system with another anti-cancer pathway, and this combination can help some patients whose cancer was not controlled by BCG alone.
Efficacy Data Supporting This Expansion
Anktiva's CIS indication was approved based on a trial (NCT03022825) that evaluated efficacy in 77 adult patients, some of whom also had papillary tumors. Most patients achieved a complete response, meaning no high-grade cancer was detected at follow-up assessments; among these patients, more than half maintained response for at least 12 months and 40% for at least 24 months.
In the review for this expanded indication, FDA considered the above results and clinical and laboratory evidence showing that CIS and high-grade papillary tumors share multiple important characteristics: they often occur together, are often difficult to distinguish under the microscope, and both face a high risk of recurrence or progression after BCG treatment failure. These similarities support extrapolating the efficacy evidence for Anktiva in patients with CIS to patients with high-grade papillary-only disease.
To help developers apply this approach, FDA is working to finalize its draft guidance, "BCG-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment." The guidance is intended to include relevant discussion on how evidence from studies in patients with CIS can be used to support approval of therapies for BCG-unresponsive, high-grade papillary-only NMIBC.
Dosage and Safety
Anktiva and BCG are administered directly into the bladder via a catheter once weekly for six consecutive weeks; subsequent treatment depends on cancer response and can last up to 37 months. Treatment should be stopped if cancer persists after a second six-week course, or if recurrence, progression, or intolerable adverse reactions occur.
The most common adverse reactions and laboratory abnormalities include painful urination or urinary frequency, urgency, hematuria, urinary tract infection, muscle or joint pain, chills, fever, and increased blood creatinine and potassium. Anktiva's prescribing information warns that delaying surgery to remove all or part of the bladder may allow cancer to spread to other parts of the body and may be fatal.
