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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Tuesday, July 28, 2015

The U.S. Food and Drug Administration has granted breakthrough therapy designation to Azedra (Ultratrace iobebguane I 131) for the treatment of patients with iobenguane-avid metastatic or recurrent pheochromocytoma and paraganglioma. Azedra is a radio-therapeutic agent.

 

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.

 

Azedra is currently being evaluated in a Phase IIb trial. The drug has also previously received orphan drug and fast track designations from the FDA.

 

Azedra is marketed by Progenics Pharmaceuticals, Inc.


Tuesday, July 28, 2015

The U.S. Food and Drug Administration has granted breakthrough therapy designation to lenvatinib (marketed under the brand name, Lenvima, by Eisai Inc.) for the treatment of patients with advanced or metastatic renal cell carcinoma who were previously treated with a vascular endothelial growth factor (VEGF)-targeted therapy. Lenvatinib is a receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor receptors VEGFR1-3.

 

Lenvatinib was approved earlier this year for the treatment of patients with differentiated thyroid cancer whose disease has progressed despite receiving radioactive iodine therapy (OT 3/10/15 issue).

 

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 new designation for lenvatinib was based on the results of a Phase II open-label, multicenter study of 153 patients who had previously been treated with a VEGF-targeted therapy. Patients were randomized to receive lenvatinib and everolimus, lenvatinib alone, or everolimus alone—and the combination therapy showed a clear benefit for patients in terms of progression free survival compared with the patients receiving either monotherapy (OT 7/25/15 issue). Median duration of response was longest in the patients receiving the drug combination (13.1 months), compared with the patients receiving only lenvatinib (7.5 months) or only everolimus (8.5 months).


Friday, July 24, 2015

The U.S. Food and Drug Administration has approved Kyprolis (carfilzomib) for Injection in combination with lenalidomide (Revlimid) and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior lines of therapy.

 

The approval is an expanded indication for Kyprolis, which was first approved to treat patients with multiple myeloma who have received at least two prior therapies, including treatment with bortezomib (Velcade) and an immunomodulatory therapy (OT 8/25/12 issue). Kyprolis also received priority review designation for the treatment of patients with relapsed multiple myeloma who have received at least one prior therapy (OT 4/25/15 issue).

 

The latest approval is based on data from the international, Phase III ASPIRE study of 792 patients with relapsed multiple myeloma following treatment with one to three prior regimens who were randomized to receive Kyprolis, lenalidomide, and low-dose dexamethasone used in combination, or lenalidomide and low-dose dexamethasone alone. The results, which were presented at the American Society of Hematology Annual Meeting in December, showed that patients treated with the three-drug combination had a median progression-free survival of 26.3 months, compared with 17.6 months for the patients treated with lenalidomide and low-dose dexamethasone (OT 1/10/15 issue).

 

The rate of deaths due to adverse events within 30 days of the last dose was balanced between both arms of the study. The most common causes of death occurring in patients in the three-drug arm versus patients in the two-drug arm of the trial were: cardiac disorders (3% vs. 2%), infection (2% vs. 3 %), renal (0% vs. less than 1%), and other adverse events (2% vs. 3%). The most common serious adverse events reported in the three-drug Kyprolis arm of the study compared to the two-drug arm were: pneumonia (14% vs. 11%), respiratory tract infection (4% vs. 1.5%), pyrexia (4% vs. 2%), and pulmonary embolism (3% vs. 2%). Discontinuation due to any adverse occurred in 26 percent of patients receiving the Kyprolis combination versus 25 percent of patients receiving the two-drug combination. Adverse events leading to discontinuation of Kyprolis occurred in 12 percent of patients.

 

Kyprolis is marketed by Onyx Pharmaceuticals, Inc.


Friday, July 24, 2015

The U.S. Food and Drug Administration has approved Odomzo (sonidegib, formerly LDE225) for the treatment of patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or for the treatment of patients with the disease who are not candidates for surgery or radiation therapy. Odomzo is a pill taken once a day that works by inhibiting the Hedgehog pathway, which is known to be active in basal cell cancers.

 

“Our increasing understanding of molecular pathways involved in cancer has led to approvals of many oncology drugs in difficult-to-treat diseases for which few therapeutic options previously existed,” Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a news release. “Thanks to a better understanding of the Hedgehog pathway, the FDA has now approved two drugs for the treatment of basal cell carcinoma just in the last three years.”

 

Vismodegib (Erivedge, marketed by Genentech) was the first drug approved to treat locally advanced and metastatic basal cell carcinoma (OT 2/25/12 issue).

 

Basal cell carcinoma accounts for approximately 80 percent of non-melanoma skin cancers; and rates of these cancers are increasing each year, according to statistics from the American Cancer Society.

 

Efficacy

The efficacy of Odomzo was established in a multi-center, double-blind clinical trial of patients with locally advanced basal cell carcinoma. Sixty six patients were randomized to receive Odomzo 200mg daily and 128 patients were randomized to receive Odomzo 800mg daily. Results showed that 58 percent of the patients who received the 200mg dose had their tumors shrink or disappear with the effect lasting 1.9 to 18.6 months (with approximately half of those responses lasting at least six months or longer). Response rates were similar for the patients receiving the higher dose, but side effects were more common for the patients.

 

The evaluation of tumor response for the trial was based on a composite assessment of modified Response Evaluation Criteria in Solid Tumors (mRECIST) that integrated tumor measurements obtained by radiographic assessments of target lesions (per RECIST 1.1), digital clinical photography (World Health Organization adapted criteria), and histopathology assessments (via punch biopsies). All modalities used must have demonstrated absence of tumor to achieve a composite assessment of complete response.

 

Side Effects

The most common side effects for Odomzo (for patients receiving the 200mg dose) were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus. Odomzo also has the potential to cause serious musculoskeletal-related side effects, including increased serum creatine kinase levels (with rare reports of rhabdomyolysis), muscle spasms, and myalgia.

 

Boxed Warning

Odomzo carries a Boxed Warning alerting healthcare professionals that Odomzo may cause death or severe birth defects in a developing fetus when administered to a pregnant woman. Pregnancy status should be verified prior to the start of Odomzo treatment, and both male and female patients should be warned about these risks and advised to use effective contraception.

 

Odomzo is marketed by Novartis Pharmaceuticals Corporation.


Friday, July 24, 2015

The U.S. Food and Drug Administration has granted priority review designation to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation. The drugs are oral agents used to block signaling in different sites of the same molecular pathway that promotes cancer cell growth—Tafinlar is a BRAF inhibitor and Mekinist is a MEK inhibitor.

 

Tafinlar and Mekinist had been approved as single agents in 2013 (OT 6/25/13 issue); and the drug combination therapy has been approved since last year under the FDA’s Accelerated Approval program (OT 2/10/14 issue). The approval for the combination was contingent on the results of the COMBI-d study, which was designed to evaluate the clinical benefit of the Tafinlar/Mekinist combination therapy in patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

 

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 action date for the drug combination is November 2015.

 

The double-blinded, Phase III COMBI-d study included 423 patients with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma, who were randomized to receive the Tafinlar/Mekinist combination or therapy with Tafinlar and placebo. The updated results showed that patients receiving the Tafinlar/Mekinist combination had a median survival of 25.1 months compared with 18.7 months for patients receiving Tafinlar and placebo. Seventy four percent of patients receiving Tafinlar and Mekinist were alive after one year of receiving the combination and 51 percent of the patients in that study arm were alive at two years, compared with 68 percent and 42 percent respectively for patients in the Tafinlar/placebo arm.

 

The safety results were consistent with the profile observed to date for the combination and consistent with the profile observed for Tafinlar monotherapy; no new safety concerns were observed. The most common adverse events for patients receiving the Tafinlar/Mekinist combination were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, arthralgia, hypertension, vomiting, cough, and peripheral edema.

 

There was a lower incidence of cutaneous squamous cell carcinoma (cuSCC) including keratoacanthoma with the Tafinlar/Mekinist arm (3%) compared to the Tafinlar/placebo arm (10%). Discontinuation of treatment due to adverse events occurred in 11 percent of patients in the Tafinlar/Mekinist arm compared with 7 percent of patients receiving Tafinlar/placebo.

 

Both Tafinlar and Mekinist are marketed by Novartis.

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