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MDx/CDx Focus: CHMP Positive Opinion on Exelixis' Cometriq; Kalydeco in R117H-Mutated CF

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Originally published Dec. 23.

EU's CHMP Issues Positive Opinion Exelixis' Cometriq for Medullary Thyroid Cancer

The European Committee for Medicinal Products for Human Use granted a positive opinion of the Exelixis' marketing authorization application for Cometriq (cabozantinib), which the firm is developing as a treatment for progressive, unresectable locally advanced, or metastatic medullary thyroid carcinoma.

According to the drug's indication as proposed by Exelixis, patients negative for the RET mutation or patients for whom the mutation status is not known, “possible lower benefit should be taken into account before individual treatment decisions.”

The European Commission will review CHMP's opinion on Cometriq and decide on the drug's MAA. If the European Commission approves Cometriq, Exelixis will launch the drug in EU countries next year.

Cometriq is a tyrosine kinase inhibitor that block the activity of RET, MET, and VEGFR2. In order to garner marketing approval in the EU for the drug, Exelixis submitted data from the Phase III trial EXAM, which showed that Cometriq improved progression-free survival compared to placebo.

The US Food and Drug Administration, which approved Cometriq at the end of November, also used data from EXAM. Medullary thyroid cancer develops in cells in the thyroid gland that make a hormone called calcitonin, which helps maintain a healthy level of calcium in the blood,the agency said in its approval announcement. This type of cancer may occur spontaneously or in families with certain genetic mutations that result in one or more cancers of the endocrine system, including the thyroid gland.”


Vertex Investigating Kalydeco in Cystic Fibrosis Patients with R117H Mutation

Vertex Pharmaceuticals has reported data from a Phase III study of its cystic fibrosis drug Kalydeco (ivacaftor) involving 69 patients six years and older with who have the R117H mutation.

“In the study, the mean absolute treatment difference in the change from baseline in percent predicted FEV1 between treatment with ivacaftor and placebo was 2.1 percentage points (p=0.20) and the mean relative treatment difference in percent predicted FEV1 was 5.0 percent (p = 0.06) through the 24-week treatment period among all patients (intent-to-treat analysis),Vertex reported in a statement. However, the study did not meet its primary endpoint of the change in FEV1 from baseline for the whole treatment period compared to placebo in the entire study population.

“Vertex believes that the results show a clinical benefit for patients age 18 and older with the R117H mutation, the firm stated. Vertex will meet with the FDA early next year to discuss a supplemental new drug application for CF patients with the R117H mutation.

The company plans to meet with the U.S. Food and Drug Administration (FDA) in early 2014 to discuss these data and the potential submission of a supplemental New Drug Application (sNDA) for people with the R117H mutation.

The US Food and Drug Administration approved Kalydeco in early 2012 for CF patients six and older who have at least one copy of the G551D mutation in the CFTR gene. The drug received approval from European regulators later that same year.

Meanwhile, the agency has accepted Vertex's sNDA and granted priority review for Kalydeco for people six and older who have CF and non-G551D gating mutations. Vertex is also conducting a Phase III trial for the drug in CF patients ages two and five who have a gating mutation. The firm is evaluating the drug in a proof-of-concept trial in patients ages 12 and older who have residual CFTR

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