Med Check
FDA Gives Nod to Investigational Therapies for Alzheimer’s
Two investigational therapies for Alzheimer’s disease (AD) were recently granted the Food and Drug Administration (FDA) Fast Track Designation—a classification that facilitates the development and expedites the review of medications.
One of these therapies is AZD3293, an oral beta secretase cleaving enzyme (BACE) inhibitor co-developed by Eli Lilly and AstraZeneca. Studies suggest that inhibiting BACE can prevent the formation and build-up of beta-amyloid, a hallmark of AD.
The companies are currently carrying out several trials of the BACE inhibitor, including a phase 2 placebo-controlled trial and two phase 3 trials of patients with early-stage AD. Final results for both trials, the companies predict, should be available by 2019.
Biogen Inc. was also granted FDA Fast Track status for its monoclonal antibody aducanumab.
A recent phase 1b placebo-controlled trial of 165 patients with prodromal and mild AD found that use of aducanumab was associated with a dose-dependent reduction in beta-amyloid in the brain. Exploratory data also suggested dose- and time-dependent slowing of clinical decline as measured by the Clinical Dementia Rating-Sum of Boxes and the Mini-Mental State Examination scores.
Biogen is currently testing the antibody in individuals with early AD in a phase 3 trial that aims to enroll approximately 1,350 patients, according to information on Clinicaltrials.gov. The studies are expected to be completed in early 2022.
Also this summer, Biogen together with Eisai Co. Ltd. announced that they had received approval from the FDA to begin a phase 3 trial of the BACE inhibitor E2609.
The FDA’s decision was partly based on data from placebo-controlled phase 2 clinical studies that showed that patients with early to moderate AD responded favorably to doses of E2609 at 5 mg, 15 mg, and 50 mg daily. Beta-amyloid levels in the plasma and cerebral spinal fluid were reduced in a dose-dependent manner in patients taking E2609.
Upcoming phase 3 trials will include patients with early Alzheimer’s who will receive daily 50 mg doses of E2609 or placebo daily. The primary outcome measure will be dementia severity at study endpoint which will be assessed at 24 months.
Postpartum Depression Therapy Receives FDA Breakthrough Designation
Sage Therapeutics in August announced that its investigational drug for postpartum depression, SAGE-547, a GABAA modulator delivered intravenously, has been granted Breakthrough Therapy Designation by the FDA—a classification that expedites the development and review of a drug.
The FDA’s decision was based primarily on the findings of a phase 2 trial of 21 patients who experienced severe postpartum depression within four weeks of delivery. Women taking the medication intravenously were found to have a significant reduction in their Hamilton Rating Scale for Depression scores compared with women administered placebo.
The effect of SAGE-547 was maintained through a 30-day follow-up period, and the medication was generally well tolerated.
FDA Warns About Combined Use of Opioids, Benzodiazepines
The FDA announced in August that it will require class-wide changes to the labels of all prescription opioid medications and benzodiazepines in an effort to inform health care providers and patients of the serious risks associated with the combined use of the medications.
The agency will now require boxed warnings—the FDA’s strongest warning—and patient-focused Medication Guides for nearly 400 products, including prescription opioid analgesics, opioid-containing cough products, and benzodiazepines. The warnings will describe the serious risks associated with using these medications at the same time.
The requirement came after a review by the agency found the number of patients receiving overlapping benzodiazepine and opioid analgesic prescriptions increased by 41 percent between 2002 and 2014—an increase of more than 2.5 million opioid analgesic patients receiving benzodiazepines. The review also revealed that from 2004 to 2011, the rate of emergency department visits involving nonmedical use of both drug classes increased significantly, with overdose deaths involving both drug classes nearly tripling during this period.
The agency said that it is currently examining available evidence regarding the risks of the combined use of benzodiazepines and opioids in patients who are undergoing medication-assisted treatment to treat opioid dependence.
Abuse-Deterrent Claim Retracted for Investigational Opioid Drug
In August, Endo Pharmaceuticals announced that the company had decided to withdraw its supplemental New Drug Application relating to abuse-deterrent labeling for its opioid pain medication Opana ER.
While the company initially suggested that a new version of the medication, which was released in 2012, had a special coating making it more difficult to snort, the FDA found it may have made the medication easier to prepare for injection.
“We anticipate the generation of additional data and we will seek collaboration with FDA to appropriately advance Opana ER,” Sue Hall, Ph.D., global head of R&D at Endo said in a press statement. ■
