It was a good day for biosimilar manufacturers and a bad day for Roche and its Genentech unit. Following a broadly positive FDA staff review of the first products to directly treat tumors, the Food and Drug Administration’s Oncology Drug Advisory Committee took the expected step of unanimously recommending approval for agents from Amgen and Mylan.
In the morning session, Amgen and Allergan’s ABP-215 was convincingly presented as equivalent to Roche’s bevacizumab (Avastin®), based on pharmacologic, pharmacokinetic, efficacy, and safety evaluations. Clinical studies were performed in patients with non–small cell lung cancer. The Advisory Committee voted 17-0, recommending approval of the drug for all of the originator product’s nonprotected indications:
- As first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil-based chemotherapy
- Combined with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line ABP 215-containing regimen
- As first-line treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous non–small cell lung cancer in combination with carboplatin and paclitaxel
- For the treatment of glioblastoma with progressive disease in adult patients following previous therapy as a single agent
- For the treatment of metastatic renal-cell carcinoma in combination with interferon alfa
- In combination with paclitaxel and cisplatin or paclitaxel and topotecan for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix
Several questions brought up by the Committee involved the glioblastoma indication, and the drug’s passage over the blood–brain barrier. Progressive multifocal leukoencephalopathy was also mentioned, but this did not deter the Committee from its unanimous vote.
Amgen did not apply for approval for Avastin’s other orphan indications, which are “protected,” according to FDA. If they did want to obtain approval for those, an additional data package would need to be submitted.
Immunogenicity studies did not reveal any material differences between the biosimilar and originator product. In a minor twist, Amgen did the clinical testing of its biosimilar against the EU-licensed version of Avastin, and it had to conduct bridging studies to demonstrate the similarity between the EU version and the US-licensed originator drug.
In the day’s second session, Mylan’s MYL-1401O, a biosimilar version of Roche’s Herceptin (trastuzumab), was evaluated. The totality of evidence, according to the FDA staff review documents, supported the 351(k) application by Mylan. The Advisory Committee agreed, voting 16-0 to recommend the biosimilar for approval for use in Herceptin’s indications:
- For use as adjuvant treatment of HER2 overexpressing node- positive or node-negative (ER/PR negative or with one high risk feature) breast cancer (1) as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; (2) with docetaxel and carboplatin; or (3) as a single agent following multimodality anthracycline-based therapy
- In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer
- As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
- In combination with cisplatin and capecitabine or 5- fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.
The FDA usually accepts the recommendation of its Advisory Committees in issuing final decisions. However, in late June, the agency rejected Pfizer’s Retacrit despite a 14–1 Advisory Committee vote to recommend, based on potential problems at a manufacturing facility. Mylan’s manufacturing partner Biocon, has recently been cited by French inspectors in connection with its European approval application, for potential problems at its Bangalore plant.