The FDA has extended its decision deadline by 3 months on a biologics license application (BLA) for MYL-1401O, a trastuzumab (Herceptin) biosimilar co-developed by Mylan and Biocon. Under the new timeframe, a final decision is expected on or before December 3, 2017.
The companies submitted the BLA to the FDA in November 2016, and the agency had set an action deadline of September 3, 2017. In July 2017, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 16-0 to recommend approval of MYL-1401O.
News of the delay was posted in a statement on Biocon’s website:
“The US FDA has notified our partner Mylan that they will extend the target action date for their Trastuzumab 351(k) application to December 3, 2017, in order to review some of the clarificatory information submitted to them as a part of the application review process. This 3-month extension has no impact on the anticipated timetable for commercialization of this product in the United States.”
Mylan and Biocon are looking to license MYL-1401O in the United States as a treatment for adjuvant breast cancer, metastatic breast cancer, and metastatic gastric cancer, the same indications as trastuzumab. Genentech, the manufacturer of trastuzumab, holds an exclusive license for the metastatic gastric cancer indication. The companies cannot market the drug for that purpose until the exclusive license expires.
The BLA includes phase III results from HERiTAge, a 2-part, multicenter, double-blind, randomized, parallel-group study. Patients with measurable HER2-positive metastatic breast cancer who had not received prior chemotherapy or trastuzumab for metastatic disease were randomly assigned to MYL-1401O (n =230) or trastuzumab with docetaxel or paclitaxel (n = 228).
Patients underwent a minimum of 8 cycles in Part 1 of the trial, with trastuzumab continuing until progression. Both forms of trastuzumab were administered with a loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg every 3 weeks.
In Part 2, patients who had stable disease or better could continue with MYL-1401O or trastuzumab. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival, overall survival, time to progression, safety, and tolerability.
MYL-1401O demonstrated an ORR after 24 weeks of 69.6% among women who received the biosimilar in combination with a taxane compared with a 64% ORR for patients who took trastuzumab plus a taxane. The ratio of ORR for MYL-1401O to trastuzumab was 1.09—both 90% CI (0.974-1.211) and 95% CI (0.954-1.237). The difference in ORR between the 2 arms was 6.0% (90% CI, -1.3%-13.2%). At the week 48 cutoff, the median duration of response was 9.7 months in both groups.
In the per protocol population, ORR was 70% for MYL-1401O compared with 67% for trastuzumab. The ratio of ORR was 1.06 (90% CI, 0.96-1.18).
Progression-free survival was nearly identical between the 2 groups (stratified HR, 0.95; 95% CI, 0.71-1.25). Median overall survival had not been met in either group.
Safety data also were comparable. Serious adverse events (AEs) occurred in 39.3% of the patients in the MYL-1401O arm compared with 37.0% in the trastuzumab arm, with neutropenia as the most frequently reported serious AE in both arms (57.5% vs 54.1%, respectively).
The BLA also included 2 nonclinical animal studies: a single-dose comparative pharmacokinetic study in cynomolgus monkeys comparing MYL-1401O to EU-trastuzumab, and a 4-week, repeat-dose toxicity and toxicokinetic study in cynomolgus monkeys comparing MYL-14010 to EU-trastuzumab.
Additional data were provided from the single-dose, randomized, double-blind comparative MYL-HER-1002 pharmacokinetic study. In the study, 120 healthy male subjects were given an 8 mg/kg infusion of MYL-1401O (n = 42), US-approved trastuzumab (n = 37), or EU-approved trastuzumab (n = 41). The predefined PK endpoints were AUC0-∞, AUC0-t, and CMax
In a briefing document used for the July ODAC meeting, FDA staff concluded that data from MYL-HER-1002 showed that MYL-1401O demonstrated a similar PK profile with US- and EU-approved trastuzumab (see table).