The European Medicines Agency's Committee for Medicinal Products for Human Use has recommended conditional marketing authorization for Amgen's Vectibix (panitumumab) after re-examining the company's application.

In a final positive opinion adopted Sept. 20, the CHMP recommended approval of the biologic as monotherapy for the treatment of patients with EGFR-expressing metastatic colorectal carcinoma with non-mutated (wild-type) KRAS after failure on fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

The agency said it recommended marketing authorization on a conditional basis "since there is more information to come about the medicine, in particular its safety and efficacy in patients according to their KRAS status."

In May, the CHMP refused marketing authorization of the epidermal growth factor receptor inhibitor, citing concerns over treatment benefits compared to risks (¹ Also see "One-Two Punch For Amgen: EMEA Rejects Vectibix, Recommends Approval For Roche's Mircera" - Pink Sheet, 25 May, 2007.).

At the time, the agency said flaws in the design of the study used to support the application failed to show sufficient evidence of a benefit from Vectibix treatment because many patients who had received standard care alone in the start of the study were later treated with Vectibix after their disease had progressed.

Amgen subsequently requested the re-examination, for which the company provided additional analysis.

"As part of the re-examination, the Committee looked at the results of the main study separately in patients whose tumors contained KRAS that had not mutated, and those where the KRAS gene contained a mutation," the CHMP explained.

"The CHMP accepted that the additional methods of analysis allowed the main study's results to be treated with more confidence, despite the way the study was designed."

In the patients whose tumors contain KRAS without any mutation, treatment with Vectibix led to a "small increase in the time until the disease got worse or the patient died." In addition, the agency said the side effects from Vectibix were similar to those seen in other drugs in its class, and were not a major concern.

"Overall, the CHMP concluded that the benefits of Vectibix outweigh its risks in patients whose tumors do not have mutations in KRAS."

Although the CHMP's reversal is a positive development for Amgen, Wall Street does not appear overly impressed by Vectibix's prospects in Europe.

"While this might represent a minor psychological positive for [Amgen], we expect peak EU sales of Vectibix to be modest given intense competition from Erbitux [Bristol-Myers Squibb/ImClone's cetuximab]," Bear Stearns analyst Mark Schoenebaum maintained in a Sept. 21 note.

Panitumumab cleared FDA in September 2006 under the accelerated approval program for the treatment of EGFR-expressing metastatic CRC following chemotherapy, even though pivotal trial data failed to show evidence of an impact on overall survival (² Also see "Amgen Vectibix Approved For Metastatic Colorectal Cancer" - Pink Sheet, 27 September, 2006.).

The CHMP separately issued two opinions for Wyeth oncologics, one positive and one negative.

The committee recommended marketing authorization approval for Torisel (temsirolimus) as a first-line therapy for patients with advanced renal cell carcinoma who have at least three of six prognostic risk factors.

The agency refused marketing authorization for the acute myeloid leukemia agent Mylotarg (gemtuzumab). The CHMP said that the benefits of the drug do not outweigh the risks of side effects, which included severe and long-lasting bone marrow suppression causing low levels of white blood cells and platelets, liver problems, and side effects related to the infusion, such as chills, fever and low blood pressure.

The CHMP said that while some patients whose disease had come back after one previous course of treatment achieved complete remission, "it was difficult to compare the effectiveness of Mylotarg and other treatments used for this disease, in terms of how long remission would last, how long it would take until the disease got worse or what the medicines' effects would be on survival."

Wyeth said it will work with the CHMP to address its concerns and will ask for a re-examination in the next two weeks.

-Brooke McManus (b.mcmanus@elsevier.com)

EMEA Recommends Conditional European Marketing Authorization For Amgen's Vectibix

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