Month: July 2017

Boehringer May Seek Interchangeable Designation for Adalimumab Biosimilar

The US Food and Drug Administration (FDA) announced earlier this year its draft standards for assessing the interchangeability of biosimilars with originator products. One biosimilar developer announced on July 27 that it is embarking on a study specifically to prove interchangeability of its biosimilar version of adalimumab.

Initial recruitment of the “VOLTAIRE-X Pharmacokinetics, Safety, Immunogenicity and Efficacy of BI 695501 Versus Humira® in Patients With Moderate to Severe Chronic Plaque Psoriasis: A Randomized, Double-Blind, Parallel-Arm, Multiple-Dose, Active Comparator Trial” was announced by Boehringer Ingelheim to provide evidence that its investigational biosimilar BI 695501 can be substituted for Humira without significant negative clinical or safety effects. The study will incorporate repeated switching between the originator and the biosimilar agent in 240 patients with plaque psoriasis.

Boehringer’s 351(k) application for BI 695501 was sent to FDA in January 2017. A decision is expected in the fourth quarter. The clinical studies supporting BI 695501 were conducted in patients with rheumatoid arthritis; another is underway in patients with active Crohn’s disease. The VOLTAIRE-X interchange study will not be completed until July 2019; therefore, any FDA decision regarding interchangeability on this biosimilar will be made at least 2 years from now.

FDA Advisory Committee Unanimously Recommends Approval for Avastin® and Herceptin® Biosimilars

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.

A final FDA decision is expected for Amgen’s bevacizumab biosimilar by September 14, and for Mylan’s trastuzumab biosimilar by September 3.

Biosimilar Rituximab Under FDA Review

Celltrion announced June 30, 2017 that it has submitted its 351(k) application to the Food and Drug Administration for approval of its biosimilar version of rituximab. This represents the first biosimilar application for rituximab, a monoclonal antibody to CD20.

The product, known during investigations as CT-P10, was approved in the European Union in February, and has been launched there as Truxima in late April. Clinical data have been presented on this biosimilar’s efficacy and safety in treating rheumatoid arthritis and advanced follicular lymphoma, a form of non-Hodgkin lymphoma

If approved, Celltrion will market this product with Teva in North America, which signed a partnership agreement with Celltrion in October 2016 for this biosimilar agent to treat cancer and for CT-P6 (trastuzumab). The FDA application for trastuzumab is expected to be filed this summer. It is currently partnered with Pfizer to market its product Inflectra® (infliximab-dyyb) in the US and Canada.

Also in June, Sandoz received approval from the European Medicines Agency to market its own version of rituximab, called Rixathon™.

In other biosimilar news…Coherus Biosciences, which took hits from the FDA and its investors in the rejection of its pegfilgrastim biosimilar in June, laid off 51 workers (about 30% of its workforce) in an effort to cut costs. Coherus is working towards addressing the issues outlined in FDA’s Complete Response Letter on pegfilgrastim. In its letter, FDA did not require additional clinical studies. In the meantime, Coherus still is seeking to file its biosimilar etanercept for approval in Europe later this year, and its version of adalimumab in the US in early 2018. However, John Carroll reported that Coherus’ clinical development partner on etanercept in Japan, Daiichi Sankyo, has decided to pull out because of concerns that Coherus will not be able to manufacture the product.