Michael J. Berendt, PhD
The FDA has scheduled an advisory hearing to discuss the biologics license application (BLA) for the immunotherapy MCNA as a treatment for patients with high-risk non-muscle invasive bladder cancer following first-line bacillus Calmette-Guérin (BCG) therapy. The joint committee meeting is scheduled for November 18, 2015, and will include input from ODAC and the Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC).
The BLA for MCNA 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. In the study, 25% of patients treated with MCNA remained disease-free at 1-year. 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.
In late August, the FDA granted a priority review to MCNA for patients with high-risk non-muscle bladder cancer. The agency is currently scheduled to act on the BLA for MCNA by February 27, 2016. When accepting the submission, the FDA had announced plans to schedule an advisory meeting.
"This advisory committee is another critical step on our path towards potential approval of MCNA as the first new therapeutic for bladder cancer patients in decades," Michael J. Berendt, PhD, chief executive officer and chief scientist at Telesta Therapeutics, the company developing the immunotherapy, said in a statement. "We will continue to work with the FDA and their advisory committee in exactly the same fashion as we have conducted ourselves over the last 18 months, with full transparency, candor and scientific rigor."
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).
"We know that high-risk BCG-refractory and BCG-relapsing patients are in great need of a non-surgical option for bladder preservation, and we believe that this is exactly what MCNA will provide," Berendt said.
Findings from the phase III study exploring MCNA were initially presented at the 2011 AUA Annual Meeting. The FDA plans to make background material for the BLA available at least 2 days prior to the advisory meeting.
Endo Pharmaceuticals and Bioniche Life Sciences initially developed MCNA, as part of a joint collaboration. In 2012, Endo returned global rights for the medication to Bioniche, which later rebranded itself as Telesta in 2014. In June 2015, Telesta, which is based in Canada, received a patent for MCNA in the United States, providing intellectual property protection for the immunotherapy for 16 years.
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.
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.