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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.

Friday, September 04, 2015

The U.S. Food and Drug Administration has granted priority review designation and breakthrough therapy status to Opdivo (nivolumab) for the treatment of patients with non-squamous non-small cell lung cancer (NSCLC) that has been previously treated. Opdivo, made by Bristol-Myers Squibb, works by inhibiting the PD-1 pathway, which blocks the body's immune system from attacking cancer cells.

 

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 Adcetris for this indication is January 2.

 

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.

 

Opdivo is currently approved by the FDA for the treatment of patients with metastatic squamous NSCLC that has progressed on or after platinum-based chemotherapy (OT 4/10/15 issue), and for the treatment of patients with unresectable or metastatic melanoms who no longer respond to other drugs (OT 1/25/15 issue).

 

Approval for Opdivo for this indication will be based on data from the CheckMate 057 Phase III study that evaluated survival of patients with non-squamous NSCLC who had progressed during or after one prior platinum, doublet-based chemotherapy regimen who were randomized to receive Opdivo or docetaxel (OT 8/10/15 issue). The median overall survival was 12.2 months for patients receiving Opdivo compared with 9.4 months for those on docetaxel. The one-year survival rate for patients who received Opdivo was 51 percent for Opdivo and 39 percent for docetaxel.

 

Treatment related serious adverse reactions occurred in seven percent of patients receiving Opdivo—and grade 3 or 4 adverse reactions occurred in five percent of patients receiving the drug. The most frequent grade 3 or 4 events reported by the patients in the study were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase.

 

The most common adverse reactions reported by patients receiving Opdivo were rash, fatigue, dyspnea, musculoskeletal pain, decreased appetite, cough, nausea, and constipation.


Friday, September 04, 2015

The U.S. Food and Drug Administration has granted orphan drug designation to LOXO-101 for the treatment of patients with soft tissue sarcoma. LOXO-101 is a potent, oral, selective inhibitor of tropomyosin receptor kinase (TRK) signaling molecules.

 

The Orphan Drug designation—to encourage development of drugs in the diagnosis, prevention, or treatment of a medical condition affecting fewer than 200,000 people in the U.S.—grants a product market exclusivity for a seven-year period if the sponsor complies with certain FDA specifications, as well as tax credits and prescription drug user fee waivers. The designation does not, though, shorten the duration of the regulatory review and approval process.

 

The TRK pathways—TRKA, TRKB, and TRKC—have been implicated in several tumor types, including lung cancer, head and neck cancer, melanoma, colorectal cancer, sarcoma, and breast cancer; and LOXO-101 is currently the only TRK inhibitor in clinical development, according to a news release from the drug manufacturer, Loxo Oncology, Inc.

 

LOXO-101 is currently being evaluated in a Phase I dose escalation trial for patients with advanced solid tumors.


Wednesday, September 02, 2015

The U.S. Food and Drug Administration has approved Emend (aprepitant) capsules for use in combination with other antiemetic agents for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in patients as young as 12, as well as for patients younger than 12 who weigh at least 30kg (approximately 66 pounds). Emend, a substance P/neurokinin 1 (NK1) receptor antagonist, is approved from chemotherapy-induced nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (including high-dose cisplatin), as well as moderately emetogenic cancer chemotherapy.

 

With this approval, Emend is the first and only NK1 receptor antagonist to be approved for the prevention of acute and delayed phases of chemotherapy-induced nausea and vomiting in patients 12 to 17, and patients younger than 12 who weigh at least 30kg. Emend was previously approved for adults for use in combination with other anti-nausea and anti-vomiting drugs for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of chemotherapy known to cause these problems (OT 5/10/03 issue).

 

Emend has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting.

 

The safety and efficacy for this expanded approval for Emend was evaluated in a randomized, double-blind, active-comparator-controlled clinical study that assessed Emend used in combination with ondansetron compared to ondansetron alone in 63 patients 12 to 17 and 69 patients younger than 12 who weighed at least 30kg, all of whom were receiving either highly emetogenic chemotherapy or moderately emetogenic chemotherapy. Intravenous dexamethasone was permitted at the discretion of the physician. For all the patients: 49.2 percent of those receiving the Emend combination had no vomiting, no retching, and no use of rescue medication in the 25 to 120 hours following initiation of chemotherapy, compared with 18.8 percent of the patients receiving the combination without Emend. Also, 55.6 percent of those receiving Emend had no vomiting, no retching, and no use of rescue medication during the first 24 hours, compared with 37.7 percent of those receiving the combination without Emend; and for the full 120 hours after initiation of chemotherapy, 34.9 percent of the patients receiving Emend had no vomiting, no retching, and no use of rescue medication, compared with 13 percent of the patients not receiving Emend.

 

The most common adverse reactions were neutropenia, headache, diarrhea, decreased appetite, cough, fatigue, hemoglobin decreased, dizziness, and hiccups.

 

Emend is contraindicated in patients with any known sensitivity to any component of this drug. Emend is also contraindicated for patients taking pimozide.

 

Emend is marketed by Merck.


Wednesday, September 02, 2015

The U.S. Food and Drug Administration has approved Varubi (rolapitant) in combination with other antiemetic agents for adults to prevent delayed phase chemotherapy-induced nausea and vomiting. Varubi is a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors with a plasma half-life of approximately seven days. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by certain cancer chemotherapies, particularly in the delayed phase.

 

“Chemotherapy-induced nausea and vomiting remains a major issue that can disrupt patients' lives and sometimes their therapy,” Amy Egan, MD, MPH, Deputy Director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, said in a news release. “Today’s approval provides cancer patients with another treatment option for the prevention of the delayed phase of nausea and vomiting caused by chemotherapy.”

 

Delayed phase chemotherapy-induced nausea and vomiting includes any nausea and vomiting that occurs from 24 hours to up to 120 hours after the start of chemotherapy. Varubi is approved for the treatment of such nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, both emetogenic and highly emetogenic. Varubi is a 180 milligram oral tablet that should be administered approximately one to two hours prior to chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

 

Varubi’s safety and efficacy were evaluated in three randomized, double-blind, controlled clinical trials that, combined, included 2,800 patients receiving highly or moderately emetogenic chemotherapy drugs. Patients received Varubi in combination with granisetron and dexamethasone or they received a combination of granisetron, dexamethasone, and placebo. Patients treated with Varubi combination had greater reduction in vomiting and use of rescue medication for nausea and vomiting during the delayed phase compared with the patients receiving the placebo combination.

 

Varubi inhibits the CYP2D6 enzyme, which is responsible for metabolizing certain drugs. Varubi is contraindicated with the use of thioridazine, a drug metabolized by the CYP2D6 enzyme, because use of the two drugs together may increase the amount of thioridazine in the blood and cause an abnormal heart rhythm that can be serious.

 

The most common side effects in patients treated with Varubi include neutropenia, hiccups, decreased appetite, and dizziness.

 

Varubi is marketed by Tesaro Inc.


Tuesday, September 01, 2015

The U.S. Food and Drug Administration has granted priority review designation to Empliciti (elotuzumab) as a combination therapy for the treatment of patients with multiple myeloma who have received one or more prior therapies. Empliciti is an investigational monoclonal antibody targeted against Signaling Lymphocyte Activation Molecule (SLAMF7, also called CS1), a glycoprotein expressed on myeloma and natural killer cells, but that is not detectable in normal tissue.

 

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 Empliciti for this indication is February 29.

 

Empliciti has previously been granted breakthrough therapy designation (OT 6/25/15 issue), which expedites  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.

 

Empliciti has been evaluated in the randomized, open-label, Phase III ELOQUENT-2 trial of 646 patients with relapsed or refractory multiple myeloma (OT 6/10/15 issue). Patients were randomized to receive a standard lenalidomide-dexamethasone or a lenalidomide-dexamethasone-Empliciti combination. The lenalidomide-dexamethasone-Empliciti combination improved progression-free survival compared with lenalidomide-dexamethasone at one year—68 versus 57 percent; and two-year progression-free survival rates were 41 versus 27 percent, respectively.

 

Additionally, the drug was evaluated in the randomized, open-label, Phase II CA204-009 study, which compared treatment with Empliciti with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in 152 patients with relapsed or refractory multiple myeloma. For the patients receiving the combination with Empliciti, 39 percent survived one year without progression of their cancers, compared with 33 percent of the patients receiving the combination therapy without Empliciti. Median progression free survival for the Empliciti combination therapy was 9.7 months versus 6.9 months for the combination therapy without Empliciti during the one-year follow up period.

 

The name Empliciti was recently proposed by Bristol-Myers Squibb, who markets the drug, and would be the drug’s brand name if approved. The drug is being co-developed by Bristol-Myers Squibb and AbbVie.

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