Med Check

Takeda Pharmaceutical Company Ltd. and H. Lundbeck A/S announced in February that the FDA Psychopharmacologic Drugs Advisory Committee voted 8-2 to expand the indication for the antidepressant Brintellix (vortioxetine) to include cognitive dysfunction in adults with major depressive disorder (MDD).

The committee’s decision was based on data presented by the two companies from two eight-week, randomized trials with approximately 1,000 people with MDD that showed Brintellix (at 10 mg/day and 20 mg/day) demonstrated a statistically significant improvement in cognitive performance over placebo and the antidepressant duloxetine.

The advisory committee’s recommendation for Brintellix will be considered by the FDA during its review of the Brintellix supplemental new drug application. The agency is expected to make a final decision by March 28.

Last month, Pfizer Inc. updated its pipeline drugs program, which excluded the clinical trial program for its novel Alzheimer’s medication PF-05212377 . According to ClinicalTrials.gov, the program was discontinued on October 23, 2015.

The trial of PF-05212377, which targets serotonin 6 (5-HT6) receptors, included people with mild-to-moderate Alzheimer’s disease with existing neuropsychiatric symptoms who were taking a stable dose of donepezil for these symptoms.

According to ClinicalTrials.gov, the trial was terminated after the medication failed to meet key endpoints for the phase 2 trial.

Other companies investigating similar drugs that target 5-HT6 receptors intended for Alzheimer’s disease have reported no or mild success with the pharmacoagents. H. Lundbeck A/S and Otsuka Pharmaceutical Co. Ltd. have reported that their co-developed drug Lu AE58054 cleared a midstage primary endpoint, but failed on all secondary endpoints. According to FierceBiotech, GlaxoSmithKline did away with its program for its 5-HT6-targeting medication in December 2014 after it failed multiple times in meeting endpoint in midstage studies.

On January 29, Allergan Plc. announced that its intravenous formulation of a novel NMDA receptor partial antagonist rapastinel (formally known as GLYX-13 ) received a Breakthrough Therapy designation by the Food and Drug Administration for adjunctive treatment of major depressive disorder. This designation is meant to expedite the development and review of potential new medicines intended to treat serious or life-threatening diseases or that have preliminary clinical evidence of demonstrating substantial effectiveness over existing therapies.

According to Allergan, the new designation by the FDA was based on preclinical and preliminary clinical evidence suggesting that rapastinel has a rapid and sustained antidepressant effect. Rapastinel was observed to be well tolerated, with no psychotomimetic or hallucinogenic side effects observed.

According to the company, Allergan plans to initiate phase 3 studies of rapastinel in 2016.

Neos Therapeutics Inc. announced that the FDA approved Adzenys XR-ODT for the treatment of attention-deficit/hyperactivity disorder (ADHD) in patients aged 6 years and older. The recent approval makes the amphetamine the first and only extended-release orally disintegrating tablet (ODT) for the treatment of ADHD.

According to a statement by the company, “Adzenys XR-ODT was approved by the FDA via the 505(b)(2) regulatory pathway. The clinical program demonstrated that Adzenys XR-ODT is bioequivalent to a previously approved mixed amphetamine salts extended-release capsule ( Adderall XR ).” Adzenys XR-ODT will be available in six dosage strengths, equivalent to Adderall dosage strengths.

The most common adverse reactions reported by patients of all ages who took Adzenys XR-ODT included loss of appetite, insomnia, and abdominal pain. Additional side effects in adults who took Adzenys XR-ODT included tachycardia, urinary tract infections, and agitation.

Patients should not take Adzenys XR-ODT if they are hypersensitive to amphetamine or are taking or have taken monoamine oxidase inhibitors within the past 14 days.

In January, the U.S. Supreme Court declined to hear an appeal from Janssen Pharmaceuticals Inc. on being assessed more than $124 million in penalties related to deceptive marketing of the antipsychotic Risperdal .

In 2011, a South Carolina state court jury had found the company guilty of downplaying to clinicians the potential health risks associated with Risperdal such as diabetes and improperly claiming that Risperdal was safer than competing medications. At that time, a penalty of $327 million was imposed.

On appeal to the South Carolina Supreme Court, the jury’s findings were upheld, and the penalty to Janssen was reduced to $236 million. The court later corrected a mathematical error and lowered the penalty to $124 million.

In an appeal to the highest court, Janssen argued that South Carolina violated the First Amendment by penalizing the company for the content of its speech without requiring proof that the speech contained “a knowing or reckless falsehood.” The company also believed that the $124 million penalty was excessive and that the South Carolina law was preempted by federal drug laws.

On January 14, the Government Accountability Office (GAO) released a report outlining a host of shortcomings in the system that the FDA uses for tracking drug safety issues, citing incomplete, outdated, and inaccurate information for postmarketed drugs.

For instance, the GAO found that the FDA was late in reviewing more than half of the 1,400 follow-up studies it had requested or required of drugmakers between 2008 and the fall of 2013. Such studies are critical for catching safety issues that may not appear until after patients start taking the drugs, according to a report by the Associated Press. The agency also admitted to GAO investigators that the majority of potential safety issues identified by staffers had not been uploaded to its archival drug tracking system, according to the AP report.

The Department of Health and Human Services, which oversees the FDA, said that the FDA will conduct internal evaluations to improve the computerized tracking system. ■