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FDA Actions for Abraxane, Arzerra, Generic Capecitabine, and Tafinlar/Mekinist Combination

doi: 10.1097/01.COT.0000436592.32336.bc


The U.S. Food and Drug Administration has expanded the approved uses of Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound) to treat patients with late-stage pancreatic cancer. Abraxane, a chemotherapy drug that slows tumor growth, is intended to be used with the chemotherapy drug gemcitabine in patients with pancreatic cancer that has spread to other parts of the body. Surgery is currently the only option to permanently remove or cure pancreatic cancer.

“Patients with pancreatic cancer are often diagnosed after the cancer has advanced and cannot be surgically removed,” Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research, said in a news release. “In these situations, and in situations when the cancer has progressed following surgery, options like Abraxane can help prolong a patient's life.”

The drug, which is marketed by Celgene, was reviewed under the FDA's priority review program, which shortens the time to complete a drug's review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act. Abraxane was also granted orphan product designation for pancreatic cancer because it is intended to treat a rare disease or condition.

Abraxane's approval was based on a clinical trial of 861 patients randomly assigned to receive Abraxane plus gemcitabine or gemcitabine alone. Patients treated with Abraxane plus gemcitabine lived 1.8 months longer than those treated with gemcitabine alone, on average, and progression-free survival for the patients receiving the drug combo was also 1.8 months longer than patients receiving gemcitabine alone.

The most common side effects for patients receiving the combination were neutropenia, thrombocytopenia, fatigue, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, pyrexia, vomiting, rash, and dehydration. The most common serious side effects were pyrexia, dehydration, pneumonia, and vomiting. Additional clinically important serious side effects included sepsis and pneumonitis.

Abraxane is also approved to treat breast cancer (OT 12/10/05) and non-small cell lung cancer (OT 12/10/12).

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Arzerra Granted Breakthrough Designation for Previously Untreated CLL

The agency granted breakthrough therapy designation for Arzerra (ofatumumab) to be used in combination with an alkylator-based therapy (such as chlorambucil) for the treatment of patients with chronic lymphocytic leukemia who have not received prior therapy and are not candidates for fludarabine-based therapy. Arzerra is a human monoclonal antibody that targets an epitope on the CD20 molecule encompassing parts of the small and large extracellular loops.

The breakthrough therapy designation, enacted as part of the FDA's 2012 Safety and Innovation Act, was created to expedite the development and review time of a potential new drug for serious or life-threatening disease where early clinical evidence suggests the drug may demonstrate substantial improvement compared with existing therapies.

The breakthrough therapy designation for Arzerra was based on the results from an international, multicenter, randomized Phase III clinical trial that included more than 400 patients with previously untreated CLL. Initial results from the trial were announced in May, and the full study results have been submitted for presentation at the ASH Annual Meeting in December.

Arzerra is being developed under a co-development and commercialization agreement between Genmab and GlaxoSmithKline.

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Approval for First Generic Capecitabine for Colorectal and Breast Cancers

Another recent FDA action was approval of the first generic version of capecitabine (Xeloda), an oral chemotherapy agent used to treat metastatic colorectal and breast cancers. The generic version is marketed by Teva Pharmaceuticals USA, and has been approved in 150 and 500 milligram strengths.

“Generic drugs are important options that allow greater access to health care for all Americans,” Kathleen Uhl, MD, acting Director of the Office of Generic Drugs in the FDA's Center for Drug Evaluation and Research, said in a news release. “This medication is widely used by people living with cancer, so it is important to have access to affordable treatment options.”

In the clinical trials for Xeloda, the most commonly observed adverse reactions included: diarrhea; vomiting; nausea; pain, redness, swelling, or sores in the mouth; hand-and-foot syndrome; and fever or infection.

Capecitabine has a boxed warning to alert health care professionals and patients about its ability to increase the effect of blood-thinning medications, such as warfarin, which potentially lead to serious side effects.

Generic drugs approved by the FDA have the same high quality and strength as brand-name drugs, the agency notes. Generic drug manufacturing and packaging sites must pass the same quality standards as those of brand-name drugs.

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Tafinlar/Mekinist Combination Granted Priority Review for Metastatic Melanoma

The FDA granted priority review designation for the combined use of Tafinlar (dabrafenib) and Mekinist (trametinib) for the treatment of adults with metastatic melanoma with a BRAF V600 E or K mutation. Both Tafinlar (a BRAF inhibitor) and Mekinist (a MEK inhibitor) were approved as single agents earlier this year (OT 6/25/13 issue).

The FDA's priority review designation shortens the time to complete a drug's review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA). The FDA has assigned a PDUFA target date of Jan. 8, 2014 for the Mekinist supplement and Jan. 9, 2014 for the Tafinlar supplement.

The applications for both drugs are based on data from a randomized Phase I/II study comparing combination therapy with dabrafenib and trametinib with dabrafenib monotherapy in adults with BRAF V600E and V600K mutation positive metastatic melanoma.

Use of dabrafenib and trametinib in combination is investigational and has not yet been approved elsewhere in the world. The combination therapy for adult patients with metastatic melanoma with a BRAF V600 mutation is also under review in Europe according to standard timelines for regulation and approval.

Both drugs are marketed by GlaxoSmithKline.

Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.
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