Med Check

In midwinter, the European Medicine Agency (EMA) accused India-based drugmaker GVK Bioscience of falsifying clinical-trials data for approximately 700 generic drugs—which included the antipsychotic quetiapine , commonly used antidepressants escitalopram and venlafaxine , and the anxiolytic clonazepam .

According to the EMA, the recommendation is based on findings from an inspection that raised concerns about electrocardiogram-generated data from studies conducted at GVK’s Hyderabad site dating back at least five years. The agency stated in a press release that the “systematic nature [of the studies], the extended period of time during which they took place, and the number of members of staff involved cast doubt on the integrity of the way trials were performed at the site generally and on the reliability of data generated at that site.” EMA did not recommend suspension of Hyderabad-produced generics that contained additional clinical-trials data that were generated and provided by sources outside of GVK.

Because the EMA has expressed doubts about the integrity of trials performed at the Hyderabad site, GVK said in a statement that it has suspended studies being conducted there with plans to redo all the studies in question at another GVK facility. However, the company has denied any wrongdoing.

Johnson & Johnson (J&J) knew that its atypical antipsychotic Risperdal could either “probably or very likely” have caused breast development in boys years before it was marketed to children, testified David Kessler, M.D., J.D., former commissioner of the Food and Drug Administration, in a Philadelphia court in late January.

According to Kessler, a 2001 clinical trial funded by J&J showed that 3.8 percent of young male participants given Risperdal developed breasts, a condition known as gynecomastia. In 2006, the company added a warning about the side effect to the drug’s official label. This “certainly was a red flag,” he stated.

Under oath, Kessler reported that in years leading to the drug’s approved use in children, J&J encouraged physicians to prescribe Risperdal through “off-label” marketing with trinkets such as children’s Lego-like blocks in bright colors adorned with the Risperdal logo.

Kessler’s testimony backed two Alabama parents who sued on behalf of their son, who had been taking the antipsychotic for five years before the drug was FDA-approved for use in children with autism spectrum disorder, according to the Philadelphia Inquirer. Their son, now age 20, claims that Risperdal caused him to grow breasts and accused J&J of hiding the risk.

In a statement, Robyn Frenze, a spokeswoman for J&J subsidiary Janssen Pharmaceuticals, said that Risperdal “has improved the lives of countless children and adults throughout the world … and it continues to improve patients’ quality of life today.” The company claims that it properly warned patients and their doctors about Risperdal’s risks and did not mishandle marketing of the drug.

In 2013, J&J agreed to pay $2.2 billion to settle federal and state allegations that it marketed Risperdal for off-label uses in children and the elderly. The U.S. Department of Justice deemed this one of the largest health-care frauds in history (Psychiatric News, December 13, 2013).

The phrase “dust yourself off and try again” may be applied to the pharmaceutical companies Actavis and Gedeon Richter regarding their new antipsychotic cariprazine .

Fourteen months after the dopamine D3 and dopamine D2 receptor partial agonist was rejected, Actavis has gathered new phase 3 data to demonstrate the effectiveness of its “blockbuster” hopeful in the treatment of schizophrenia.

For a double-blind study, Actavis recruited 200 patients with schizophrenia who were given 3 mg to 9 mg a day of cariprazine or placebo. The results showed that individuals taking cariprazine were 55 percent less likely to relapse within a 20-week period than patients in the placebo cohort. The most commonly reported adverse events included nasopharyngitis, tremors, back pain, and increased creatine phosphokinase in blood.

The Food and Drug Administration approved a new drug application resubmission for cariprazine submitted by Actavis in January.

Last year’s Food and Drug Administration (FDA) approval of Zohydro ER generated outrage from advocates and officials from several states who proclaimed that marketing of the hydrocodone-based painkiller would merely add to the nation’s high rates for opioid addiction—forcing makers of the controversial drug to take action.

Last month, Zogenix, manufacturer of Zohydro ER, announced that it had received a green light from the FDA for a new formulation of the painkiller through the use of BeadTek, a technology that transforms the drug into a viscous gel when crushed and dissolved in liquids or solvents. The new formulation, Zogenix claims, will maintain the efficacy and pharmacokinetic profile of the original formula if used as intended.

“While we are very pleased with the outcomes from our safe-use initiatives, implemented with the introduction of Zohydro ER last year, we believe moving forward with this formulation change at the earliest possible time is a responsible action for us to take,” said Stephen Farr, Ph.D., president of Zogenix.

Though the company plans to transition to Zohydro ER with BeadTek in the second quarter of this year, the FDA will not give Zogenix the nod for labeling the drug’s abuse-deterrent properties until such is proven by additional studies. The new formulation will be available in strengths ranging from 10 mg to 50 mg.

Switzerland-based pharmaceutical company AC Immune has announced that it will join forces with Janssen Pharmaceuticals to develop and commercialize anti-Tau vaccines for the treatment of Alzheimer’s disease (AD) and other Tau protein–related neurodegenerative diseases.

Janssen and AC Immune will co-develop AC’s lead therapeutic vaccine, ACI-35 , now in a phase 1b clinical trial with AD patients. As of phase 2, Janssen will assume responsibility for the clinical development, manufacturing, and commercialization of the biologic.

ACI-35 functions by stimulating patients’ immune system to produce antibodies against mutated Tau proteins—a hallmark of AD independent of amyloid-beta plaques. The vaccine is the first of its kind in clinical development that targets modified Tau-proteins associated with AD. ■