FDA Grants Intravesical Immunotherapy Priority Review for Bladder Cancer

Michael J. Berendt, PhD

The FDA has assigned a priority review designation to the intravesical immunotherapy MCNA as a treatment for patients with high-risk non-muscle invasive bladder cancer following first-line bacillus Calmette-Guérin (BCG) therapy, according to a statement from the drug's developers, Telesta Therapeutics.

The priority review was based on findings from an open-label phase III trial, which demonstrated significant activity with MCNA, an immunotherapy that is comprised of mycobacterial cell wall fragments complexed with nucleic acids. Under this review program, the FDA will make a decision on the application for the treatment by February 27, 2016. Prior to this date, the agency announced plans to hold an advisory meeting to discuss the application.

In the pivotal open-label phase III study, 25% of patients treated with MCNA remained disease-free at 1-year, which missed the primary endpoint of the study. However, at 2-years, the disease-free survival (DFS) rate was 19%. In patients with papillary only tumors, the DFS rate was 35.1% and 32.2% at 1 and 2 years, respectively.

Telesta submitted the biologics license application (BLA) for MCNA to the FDA in June 2015. At this time, the FDA waived $2.3 million in user fees associated with the application. Certain waivers for fees exist under the Prescription Drug User Fee Act, specifically for small companies filing their first new drug application. A new treatment has not been approved for patients with high-risk bladder cancer since 1998.

"Today is a historic day for Telesta Therapeutics and for all of our staff and collaborators who have worked so diligently to advance our new treatment for non-muscle invasive bladder cancer towards potential regulatory approval early next year," Michael J. Berendt, PhD, chief executive officer and chief scientist at Telesta, said in a statement. "While we recognize that the FDA must complete its full review of our BLA filing before rendering its ultimate decision, we are working extremely hard, at all levels, to prepare for commercial launch in the United States."

In the phase III study, 129 patients were treated with an induction dose of MCNA at 8 mg weekly. After 3 months of induction therapy, those who remained disease-free went on to receive a maintenance dose from months 3 to 24. In this portion of the study, MCNA was given in 3 weekly installments every 3 months.

Of the patients enrolled, 91 had carcinoma in situ with or without papillary disease and 38 had papillary only tumors. Most patients had high-risk disease, 107 were BCG-refractory, and 68 patients had received 2 or more prior BCG induction courses. The primary endpoint of the study was a 40% DFS rate at 1 year.

At a median 34.7-month follow-up, the median disease-free duration in responders was 32.7 months. The progression-free survival (PFS) rate at 1-year was 87.3%. At year 2 and 3, the PFS rate with MCNA was 79.8% and 77.7%, respectively.

Adverse events (AEs) experienced by patients in the trial were mild to moderate in severity and did not frequently lead to treatment discontinuation. Only 2 serious AEs were considered to be treatment-related (hematuria and urinary tract infection).

Findings from the phase III study exploring MCNA were initially presented at the 2011 AUA Annual Meeting. At the time of this presentation, Endo Pharmaceuticals and Bioniche Life Sciences were developing the treatment. In 2012, Endo returned global rights for the medication to Bioniche, which later rebranded itself as Telesta in 2014.

As part of the submission process for MCNA, Telesta completed a number of upgrades and improvements to its manufacturing facility and operating procedures. These upgrades were completed in February 2015, prior to an FDA pre-approval inspection under their formal review process.

In June 2015, Telesta, which is based in Canada, received a patent for MCNA in the United States, providing intellectual property (IP) protection for the immunotherapy for 16 years.

"We are extremely pleased with the issuance of this US composition of matter patent, which provides strong IP coverage in the largest and most important commercial market for MCNA," Berendt said. "This patent is a key component of our IP portfolio and will provide intellectual property protection for at least 16 years, which is a major advantage as we look forward to commercial approval in 2016.”

Morales A, Herr H, Steinberg G, et al. Efficacy and safety of MCNA in patients with nonmuscle invasive bladder cancer at high risk for recurrence and progression after failed treatment with bacillus Calmette-Guérin. J Urol. 2015; 193(4):1135-1143.