Med Check

Eli Lilly and Company announced negative clinical trial results in July from a study known as H8Y-MC-HBBM (HBBM) investigating pomaglumetad methionil, also known as mGlu2/3 , for treatment of acute exacerbations of schizophrenia. Lilly said the drug did not separate from placebo in the primary efficacy endpoint in either the overall or predefined genetic subpopulation (based on the Positive and Negative Syndrome Scale), at the two doses investigated (40 mg and 80 mg BID).

The active control, risperidone, did separate from placebo in both populations. Pomaglumetad methionil was generally well tolerated, with no new safety findings compared with previous trials.

HBBM was to be the first of two clinical trials to support registration of the compound for monotherapy in acute schizophrenia. The second clinical trial, H8Y-MC-HBBN (HBBN), is ongoing. The company will conduct an interim analysis of HBBN data, with results expected later this year. Additionally, Lilly is also waiting for results from the recently concluded study H8Y-MC-HBCO, a phase 2 study exploring pomaglumetad methionil as an adjunctive treatment with atypical antipsychotics.

Pomaglumetad methionil is a glutamatergic-based agent that does not interact with central nervous system receptors thought to be responsible for many of the side effects, such as motor dysfunction, reproductive hormone irregularity, weight gain, and lipid elevation, associated with current schizophrenia treatments.

The FDA has responded to a congressional report that says it is a significant cause of existing shortages of several medications. In a July 23 letter, the agency addressed the findings of a June 15 report from the House of Representatives Committee on Oversight and Government Reform (titled “FDA’s Contribution to the Drug Shortage Crisis”) that largely blamed the agency for the shortages.

“Contrary to the conclusion reached in the report, FDA is not the root cause of this serious public health problem,” wrote Jeanne Ireland, the FDA’s assistant commissioner for legislation, in the letter to Rep. Elijah Cummings (D-Md.), the committee’s ranking member. Ireland said that more than half of the drug shortages in recent years were related to manufacturing production problems, including quality-related issues and delays, and the remainder were caused by business decisions to discontinue certain products, difficulty obtaining raw materials, loss of manufacturing sites, increased demand, and component problems. Ireland contended that the FDA’s efforts show that it is part of the solution rather than the cause of the problem.

“FDA’s Contribution to the Drug Shortage Crisis” is posted at http://oversight.house.gov/wp-content/uploads/2012/06/6-15-2012-Report-FDAs-Contribution-to-the-Drug-Shortage-Crisis.pdf . The FDA’s response letter is posted at http://democrats.oversight.house.gov/images/stories/2012-5778.Cummings.drug%20shortages.response.final.pdf .

On July 6, Eli Lilly and Co. announced that it has met the Food and Drug Administration (FDA) requirements for pediatric exclusivity for Cymbalta (duloxetine HCl) . Based on this decision, Lilly has gained an additional six months of U.S. market exclusivity for Cymbalta, which now will expire in December 2013. The approval of pediatric exclusivity does not mean that Cymbalta is approved for use in pediatric patients. Cymbalta is FDA-approved only for use in adults aged 18 and older. The company said it doesn’t plan to seek a pediatric indication for Cymbalta.

Cymbalta is a serotonin and norepinephrine reuptake inhibitor approved to treat major depressive disorder and generalized anxiety disorder and to manage diabetic peripheral neuropathic pain and fibromyalgia. It is also approved for the management of chronic musculoskeletal pain in those with chronic osteoarthritis or chronic low-back pain.

The FDA has approved in quick succession two drugs intended to be used as an addition to a reduced-calorie diet and exercise for chronic weight management. Belviq (lorcaserin hydrochloride) , manufactured by Arena Pharmaceuticals and distributed by Eisai, was approved in June, followed in July by the approval of Qsymia, the phentermine/topiramate combination formerly known as Qnexa, and developed by Vivus. Both drugs were approved for use in adults with a body mass index (BMI) of 30 or greater (obese) or adults with a BMI of 27 or greater (overweight) who have at least one weight-related condition such as high blood pressure, type 2 diabetes, or high cholesterol.

Belviq works by activating the serotonin 2C receptor in the brain. Activation of this receptor may help a person eat less and feel full after eating smaller amounts of food. The safety and efficacy of Belviq were evaluated in three randomized, placebo-controlled trials that included nearly 8,000 obese and overweight patients, with and without type 2 diabetes, treated for 52 to 104 weeks. All participants received lifestyle modification that consisted of a reduced-calorie diet and exercise counseling. Compared with placebo, treatment with Belviq for up to one year was associated with average weight loss ranging from 3 percent to 3.7 percent. The drug’s manufacturer will be required to conduct six post-marketing studies, including a long-term cardiovascular outcomes trial, to assess the effect of Belviq on the risk for major adverse cardiac events such as heart attack and stroke.

Qsymia cannot be used during pregnancy because of increased risk of oral clefts (cleft lip with or without cleft palate) during the first trimester due to the topiramate component of the drug. Qsymia is also not for use in patients with glaucoma or hyperthyroidism because it can increase heart rate. Vivus will be required to conduct 10 postmarketing evaluations, including a long-term cardiovascular outcomes trial, to assess Qsymia’s on risk for major adverse cardiac events.

Palatin Technologies announced June 19 that a phase 1 clinical trial being conducted by AstraZeneca of AZD2820 , a subcutaneously administered peptide melanocortin-4 receptor partial agonist under development for obesity treatment, has been halted.

The trial was halted by the Safety Review Committee established by AstraZeneca after a serious adverse event occurred in which a study subject may have had an allergic reaction following his first dose. The subject was treated at the clinical site and has recovered, and the incident is being reviewed.

The phase 1 single-center study enrolled 72 obese but otherwise healthy male subjects, with a BMI between 30 and 35 in a randomized, single-blind, placebo-controlled trial. Eleven subjects had completed their dosing regimen prior to the trial being stopped. The primary goal of the study was to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD2820 after administration of multiple ascending doses. Another phase 1 study of AZD2820 concluded in 2011 without any reported serious adverse events.