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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.

Thursday, September 11, 2014

The U.S. Food and Drug Administration has approved a new indication for the use of Xtandi (enzalutamide) capsules to treat patients with metastatic castration-resistant prostate cancer (CRPC) who have not received prior chemotherapy. Xtandi had previously been approved for use in patients with metastatic CRPC who had received docetaxel (OT 9/25/14 issue).

 

The drug was approved after being granted priority review by the FDA, 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 (PDUFA).

 

Approval of the new indication for Xtandi is based on results of the randomized, double blind, multinational, Phase III PREVAIL trial of 1,717 men with metastatic CRPC who had not received previous chemotherapy. Treatment with Xtandi reduced risk of death by 29 percent compared with the placebo; and treatment with Xtandi reduced the risk of progression of disease or death by 83 percent compared with the placebo. Treatment with Xtandi was also found to delay time to initiation of chemotherapy, as well as time to a skeletal-related event.

 

“In the PREVAIL trial, the median time to initiating chemotherapy was delayed by 17 months with enzalutamide treatment as compared to placebo, so the result is a meaningful period of time during which men have their disease controlled without the need for chemotherapy," co-principal investigator for the study Tomasz M. Beer, MD, FACP, Deputy Director of the Knight Cancer Institute and Professor of Medicine at Oregon Health & Science University, said in a news release.

 

A serious side effect reported with use of the drug were seizure, which occurred 0.1 percent of patients who had not received chemotherapy. The most common adverse reactions occurring in patients treated with Xtandi were: asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral adema, dyspnea, musculoskeletal pain, weight loss, headache, hypertension, and dizziness/vertigo.

 

Xtandi is marketed by Astellas Pharma Inc. and Medivation, Inc.


Thursday, September 04, 2014

The U.S. Food and Drug Administration has today granted accelerated approval to Keytruda (pembrolizumab, formerly MK-3475) for the treatment of patients with advanced or unresectable melanoma who are no longer responding to other drugs. Keytruda is the first approved drug that blocks the PD-1 pathway, which prevents the body’s immune system from attacking melanoma cells.

 

"This drug is a game changer, a very significant advance in the treatment of melanoma," Antoni Ribas, MD, PhD, Professor of Medicine in the Division of Hematology-Oncology at the David Geffen School of Medicine at University of California Los Angeles, said in a news release from UCLA. Ribas served as principal investigator for the Phase I study of the drug. "For patients who have not responded to prior therapies, this drug now provides a very real chance to shrink their tumors and the hope of a lasting response to treatment."

 

Keytruda is intended for use following treatment with ipilimumab immunotherapy. For patients whose tumors express the BRAF V600 mutation, Keytruda is intended for use after treatment with ipilimumab and a BRAF inhibitor.

 

Breakthrough Therapy, Priority Review, Orphan Drug, and Accelerated Approval

The FDA granted Keytruda breakthrough therapy designation because the sponsor demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies. The drug also received priority review and orphan product designation. Priority review is granted to drugs that have the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan product designation is given to drugs intended to treat rare diseases.

 

Approximately 76,100 Americans will be diagnosed with melanoma and 9,710 will die from the disease this year, according to estimates from the National Cancer Institute.

 

Keytruda was approved as part of the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. An improvement in survival or disease-related symptoms has not yet been established.

 

“Keytruda is the sixth new melanoma treatment approved since 2011, a result of promising advances in melanoma research,” 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. “Many of these treatments have different mechanisms of action and bring new options to patients with melanoma.”

 

The five prior FDA approvals for melanoma include: ipilimumab (OT, 4/25/11), peginterferon alfa-2b (OT, 4/25/11), vemurafenib (OT, 9/10/11), dabrafenib (OT, 6/25/13), and trametinib (OT, 6/25/13).

 

Efficacy and Safety

The efficacy for Keytruda was established in a clinical trial of 173 patients with advanced melanoma whose disease had progressed after prior treatment. All participants were treated with Keytruda, either at the recommended dose of 2mg/kg or a higher dose of 10mg/kg. Of the lower dose patients, approximately 24 percent had their tumors shrink, lasting 1.4 to 8.5 months and continuing longer in most patients. Similar results were seen for the patients receiving the higher dose.

 

The safety for Keytruda was established in a trial of 411 patients with advanced melanoma. The most common side effects reported were: fatigue, cough, nausea, pruritus, rash, decreased appetite, arthralgia, and diarrhea. The drug does have the potential for sever immune-mediated side effects, though they occurred uncommonly in the trial involving the lung, colon, hormone-producing glands, and liver.

 

Phase II and III clinical studies of Keytruda in advanced melanoma are ongoing, which are designed to provide further confirmatory evidence for this indication. Keytruda is marketed by Merck & Co.


Wednesday, September 03, 2014

The U.S. Food and Drug Administration has granted priority review designation for the use of Somatuline Depot injection for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Somatuline contains lanreotide acetate, a somatostatin analogue that inhibits the secretion of several endocrine, exocrine, and paracrine amines and peptides. The drug is approved in the U.S. for the long-term treatment of patients with acromegaly who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy.

 

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).

 

GEP-NETs affect five out of every 100,000 people in the U.S., and incidence has more than quadrupled in the past 30 years, the drug’s manufacturer Ispen, noted in a press release.

 

Somatuline’s application is based on data from the randomized, double-blind, Phase III CLARINET study of 206 patients from 48 centers with well or moderately differentiated non-functioning enteropancreatic neuroendocrine tumors and a proliferation index of less than 10 percent. Patients were randomized to receive Somatuline treatment or placebo. The data found patients receiving the placebo had a median progression-free survival of 18 months and 33 percent had not progressed or died at 96 weeks; while patients receiving Somatuline did not reach the median for progression-free survival and 65.1 percent had not progressed or died at 96 weeks. These findings showed a 53 percent reduction in risk of disease progression or death.

 

The most common adverse reactions were diarrhea (37%), cholelithiasis (20%), abdominal pain (19%), nausea (11%), injection-site reaction (9%), constipation (8%), flatulence (7%), headache (7%), arthralgia (7%), vomiting (7%), and loose stools (6%). Serious side effects could include gallstones, changes in blood sugar, slow heart rate, and high blood pressure.


Friday, August 15, 2014

The U.S. Food and Drug Administration has approved a new use for Avastin (bevacizumab) for the treatment of patients with persistent, recurrent, or metastatic cervical cancer. Avastin is a biologic antibody that binds to vascular endothelial growth factor (VEGF) to prevent tumor metastasis by inhibiting tumor blood supply. The new indication for cervical cancer is approved for use in combination with chemotherapy drugs paclitaxel and cisplatin, or in combination with paclitaxel and topotecan.

 

“Avastin is the first drug approved for patients with late-stage cervical cancer since the 2006 approval of topotecan with cisplatin,” 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. “It is also the first biologic agent approved for patients with late-stage cervical cancer and was approved in less than four months under the FDA’s priority review program, demonstrating the agency’s commitment to making promising therapies available to patients faster.”

 

Avastin was granted Priority Review for this indication in cervical cancer in July. Avastin also has approved indications for the treatment of patients with metastatic colorectal cancer (OT 2/25/13 issue), and for the treatment of patients with first-line or previously untreated metastatic colorectal cancer (OT 3/25/04 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 safety and effectiveness of Avastin for this new approval for Avastin was evaluated in a clinical study of 452 patients with persistent, recurrent, or late-stage disease. Patients were randomly assigned to receive paclitaxel and cisplatin with or without Avastin, or paclitaxel and topotecan with or without Avastin. The results showed an increase in overall survival to be 16.8 months in patients who received chemotherapy and Avastin, compared with 12.9 months for patients receiving chemotherapy alone.

 

The most common side effects associated with the use of Avastin in patients with cervical cancer include fatigue, decreased appetite, hypertension, hyperglycemia, hypomagnesemia, urinary tract infection, headache, and decreased weight. Perforations of the gastrointestinal tract and abnormal openings between the gastrointestinal tract and vagina (enterovaginal fistula) also were observed in Avastin-treated patients.

 

Avastin is marketed by Genentech.


Thursday, August 14, 2014

The U.S. Food and Drug Administration has granted Fast Track designation to AG-221 for the treatment of patients with acute myelogenous leukemia (AML) that harbors an isocitrate dydrogenase-2 mutation. AG-221 is a first-in-class, oral, selective, potent IDH2 mutant inhibitor.

 

The Fast Track designation, established under the FDA Modernization Act of 1997, is designed to facilitate frequent interactions with the FDA review team to expedite clinical development and submission of a New Drug Application for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs. The designation permits the drug developer the opportunity to submit sections of an NDA on a rolling basis as data become available, allowing the FDA to review those materials on a rolling basis as well.

 

This year, approximately 18,860 patients will be diagnosed with AML, and approximately 10,460 patients with AML will die, according to the most recent American Cancer Society Facts and Figures. Approximately 20 percent of patients with AML have the IDH mutation, notes a news release from the drug’s developer, Agios Pharmaceuticals.

 

Phase I clinical trials for AG-221 are currently ongoing.

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