Med Check

Drug Company Scrutinized For Data Manipulation In ADHD Clinical Trial

“To omit, or not to omit?” may have been a question that Alcobra Pharma asked while generating data from its phase 3 clinical trial of a drug intended for attention-deficit/hyperactivity disorder (ADHD). Near the beginning of the current fiscal quarter, Alcobra announced the results from its 300-patient phase 3 study showing that its drug metadoxine (MDX), a nonstimulant that modulates gamma-aminobutyric acid (GABA), was statistically superior to placebo in improving ADHD symptoms in people who took the medication for six weeks. However, the results were scrutinized by investors due to unreported data.

According to the Alcobra, the full data set showed that MDX yielded only a “positive trend” in improving ADHD symptoms, compared with placebo. The statistical difference for effectiveness between the two groups resulted in a p value of 0.15—well short of the 0.05 threshold that is required for statistical significance. However, Albcobra noted, if four “extreme” responders are removed from the placebo group, the p value for the statistical difference between MDX and placebo groups drops to 0.03—making MDX statistically superior to placebo.

“We conducted the modified Intent to Treat analysis after observing the disproportional effect of a few extremely large placebo responses, which were inconsistent with what has been reported in previous ADHD trials of MDX or other agents,” said Alcobra Chief Medical Officer Jonathan Rubin, M.D. “We plan to take the complete findings of this and other MDX studies to the FDA to determine the next steps on the path to potential regulatory approval for MDX.”

In a press release, Alcobra stated that it plans to share the full data at future scientific and medical conferences, as well as in peer-reviewed publications.

‘Black Box’ Label on Chantix Should Stay, FDA Panel Says

In mid-October, a Food and Drug Administration (FDA) panel voted against removing a black-box warning for Pfizer’s smoking-cessation aid, Chantix (varenicline). The panel has agreed to revisit the case once data from a Pfizer-led postmarking study are made available.

The study, which includes approximately 8,000 people, compares the safety profile of Chantix with two other smoking-cessation drugs and placebo in terms of serious neuropsychological effects. Data are expected to be released in the third quarter of 2015.

The FDA put its most severe and restrictive label on Chantix in 2009, warning consumers about the product’s potential for psychiatric side effects including hostility, agitation, depressed mood, and suicidal thoughts or actions.

Since the label warning and subsequent negative press reports, Chantix sales have dropped by $200 million since 2008 and have cost Pfizer more than $275 million in settlement payouts to consumers and their families alleging that the drug triggered adverse psychiatric events, including completed suicides.

In 2011, after reviewing data from a new study, the FDA said that Chantix did not appear to increase the risk of hospitalization for psychiatric illnesses. Yet the agency decided to affirm its stance that the black-box warning was still necessary.

FDA Approves New Abilify Formulation

Otsuka and Lundbeck pharmaceutical companies received the seal of approval for their new formulation of Abilify Maintena (aripiprazole) for extended-release injectable suspension—a prefilled, dual-chamber syringe. The antipsychotic is indicated for treatment of schizophrenia.

“Since March 2013, Abilify Maintena has been an important treatment option for people living with schizophrenia,” said Robert McQuade, Ph.D., executive vice president and chief strategic officer of Otsuka. “With the approval of the dual-chamber syringe, … [we can] simplify the delivery of care for patients receiving Abilify Maintena.”

Efficacy of the new formulation was assessed in a placebo-controlled, randomized-withdrawal, maintenance trial in patients with schizophrenia. The most common side effect was akathisia.

The companies expect the dual-chamber syringe to be available in the United States in January 2015.

Kentucky Sues OxyContin Manufacturer for $1 Billion

Kentucky, among other states, has been hit hard by the opiate addiction epidemic. And according to state officials, Purdue Pharma—the maker of OxyContin—is partly to blame.

The state is suing the company for $1 billion for alleged Medicaid fraud, false advertising, and 10 other fraudulent claims—but most of all for the opiate addiction epidemic that the state claims has led to overdoses, addiction-related deaths, and drug-related crimes. The state accuses Purdue of misleading physicians and health professionals into believing that OxyContin was difficult to abuse.

Purdue refutes the lawsuit’s claims and says that the company has taken multiple steps to help prevent abuse of its drug, such as the release of company data showing that the potentially addictive painkiller can be transformed into a substance with high abuse potential by crushing the pills.

Kentucky Attorney General Jack Conway appears unmoved by the company’s sentiments. In an interview with Bloomberg, Conway stated, “I want to hold them accountable in eastern Kentucky for what they did. We have lost an entire generation. Half the pharmacies in Pike County have bulletproof glass. We had FedEx trucks being knocked off. It was the Wild West.”

According to the Bloomberg report, a trial over the state’s lawsuit may take place as early as 2015.

Positive Results Seen In Early Trials of Drug To Treat Alzheimer’s

Finally, there is a glimmer of hope for drugs targeting beta-site amyloid precursor protein cleaving enzyme (BACE) intended for the treatment of Alzheimer’s disease (AD).

Vitae Pharmaceuticals announced successful results for two phase 1 clinical trials for its BACE inhibitor BI1181181/VTP-37948, which was developed by Boehringer Ingelheim. The phase 1 studies were randomized, placebo-controlled, single-dose trials that involved 68 healthy individuals.

Results from the first study showed that those taking BI1181181/VTP-37948 had, on average, an 80 percent reduction in levels of amyloid beta protein in the cerebral spinal fluid. The second trial showed that the newly developed BACE inhibitor was safe and generally well tolerated across all dose levels tested. In addition, the results indicated a half-life of between 16 and 19 hours, indicating a potential for the pharmacotherapy to have a once-daily dosing profile.

As of last year, Lilly, Roche, and Astellas halted development of their BACE inhibitors due to unsuccessful clinical trial results. Richard Gregg, M.D., chief scientific officer of Vitae, said that though the results from current studies involving BI1181181/VTP-37948 come early in the clinical trials process, they are nevertheless encouraging for the field of Alzheimer’s research. ■