Novartis’ First CAR-T Cell Therapy Tisagenlecleucel (CTL019)

The FDA’s Oncologic Drug Advisory Committee (“ODAC”) held a public meeting on Wednesday, July 12, 2017, to consider Novartis’ biologic license application (BLA 125646) for tisagenlecleucel (CTL019), an investigational chimeric antigen receptor T cell (“CAR-T”) therapy. Novartis is seeking approval of CTL019 for the treatment of patients from three to 25 years old with relapsed or refractory B-cell acute lymphoblastic leukemia. Novartis announced last week that the committee unanimously recommended approval in a vote of 10-0.

Tisagenlecleucel is comprised of genetically-modified antigen-specific autologous T cells that have been reprogrammed to target cells that express CD19, an antigen that is expressed on the surface of B cells and tumors derived from B cells. As explained in the FDA briefing document, available here, “[t]he tisagenlecleucel chimeric antigen receptor (CAR) protein consists of an extracellular portion that has a murine anti-CD19 single chain antibody fragment (scFv) and an intracellular portion that contains T cell signaling (CD3-ζ) and co-stimulatory (4-1BB) domains. These intracellular domains play critical roles in tisagenlecleucel’s functions, including T cell activation, persistence in vivo and anti-tumor activity.” Additional meeting materials are available on the FDA’s website here.

CTL019 was originally developed by the University of Pennsylvania, and Novartis entered into a global collaboration with the university in 2013 to further research, develop, and commercialize CAR-T cell therapies, including CTL019. According to Novartis, if approved, CTL019 could become the first CAR-T cell therapy available.

Amgen and Allegan’s Proposed Bevacizumab Biosimilar (ABP 215)

On the morning of Thursday, July 13, 2017, FDA’s ODAC held a meeting to consider the approval of ABP 215, Amgen and Allergan’s proposed biosimilar to Roche/Genentech’s Avastin® (bevacizumab). As we previously discussed in this post, the FDA established a public docket for comments in advance of this meeting, and a total of nine comments (available here) were submitted to the agency prior to the meeting. The committee voted unanimously (17-0) in favor of approval.

Bevacizumab is an anti-vascular endothelial growth factor A (Anti-VEGF) specific monoclonal antibody that inhibits formation of new blood vessels and is used to slow the growth of tumors related to several types of cancers. Amgen and Allergan are seeking approval of ABP 215 for (1) metastatic colorectal cancer, with intravenous 5-fluorouracil–based chemotherapy for first- or second-line treatment; (2) metastatic colorectal cancer, with fluoropyrimidine-irinotecan- or fluoropyrimidineoxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line Avastin-containing regimen; (3) non-squamous non-small cell lung cancer, with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease; (4) glioblastoma, as a single agent for adult patients with progressive disease following prior therapy; (5) metastatic renal cell carcinoma with interferon alfa; and (6) cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease.

The FDA meeting materials including, inter alia, the FDA’s and Amgen’s briefing documents as well as draft questions are available directly from the FDA’s website here.

Mylan and Biocon’s Proposed Trastuzumab Biosimilar (MYL-1401O)

In the afternoon of Thursday, July 13, 2017, FDA’s ODAC held a meeting to consider the approval of MYL-1401O, Mylan and Biocon’s proposed biosimilar to Roche/Genentech’s Herceptin® (trastuzumab). A copy of the FDA briefing document for the proposed product is available from the FDA website here, and the other meeting materials, including a briefing document prepared by Mylan, are available here. According to Mylan’s announcement that same day, the committee voted unanimously (16-0) in favor of approval.

Trastuzumab is a monoclonal antibody that interferes with the human epidermal growth factor receptor (HER2)/neu. Mylan and Biocon are seeking approval of their proposed trastuzumab for the same indications approved for Herceptin®, including treatment of adjuvant breast cancer, treatment of patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens for their metastatic disease, and treatment of metastatic gastric cancer in combination with cisplatin and capecitabine or 5-fluorouracil.

Earlier this year, Mylan and Biocon announced that they entered into a global settlement and licensing agreement with Genentech and Roche regarding Mylan’s trastuzmab biosimilar, as we previously reported in this post. We will continue to keep you apprised of further developments with respect to all of these applications.