Med Check

Regulatory Briefs

• The maker of risperidone long-acting injection, Johnson and Johnson Pharmaceutical Research and Development (J&JPRD), announced on February 10 that it had received a “complete response letter” from the Food and Drug Administration (FDA) requesting additional information about the medication. The agency's letter was in response to the company's supplemental application, which sought approval for the new indication of adjunctive maintenance treatment for patients with bipolar disorder who relapse frequently. According to the company's announcement, the agency outlined questions that must be answered before the application can be approved, but did not require that more clinical trials be conducted.

Risperidone long-acting injection is currently approved for the treatment of schizophrenia.

• The FDA sent a complete response letter to Eli Lilly regarding its application for marketing olanzapine pamoate long-acting injection for treatment of schizophrenia. Lilly said the FDA requested the company to provide a detailed plan on postmarketing strategies for safety surveillance. The agency has been concerned about uncommon but potentially severe adverse events associated with the drug in clinical trials. These adverse events included heavy sedation, confusion, and loss of consciousness in some cases. The FDA convened an advisory-committee meeting about the medication a year ago and has not approved the product since then (Psychiatric News, March 21, 2008). Lilly said it was preparing a Risk Evaluation and Mitigation Strategy as requested and would submit it to the agency soon.

• Schering-Plough, the company seeking regulatory approval for the investigational antipsychotic drug asenapine sublingual tablets, announced on January 14 that it received the FDA's complete response letter for the new drug application. The agency asked for additional data and proposed labeling language, but did not request that the company conduct additional clinical trials. The company is seeking approval for its indications as a treatment for schizophrenia and manic or mixed bipolar disorder episodes.

• The FDA sent a warning letter to Abbott Laboratories regarding“ misbranding” information in promotional material about its products divalproex sodium delayed-release tablets (Depakote and Depakote ER). The letter noted that a pharmacy formulary flashcard omits certain risk and other important information and broadens indications in the drug information printed on the flashcard. The agency asked the company to stop distributing the materials immediately.

• The FDA issued a follow-up announcement on January 13 about the agency's safety review of potential neuropsychiatric risks associated with montelukast. In March 2008 the FDA told the public that it was closely examining clinical trial evidence for a suspected link between the asthma/allergy drug and reports of mood changes, suicidal thoughts and behaviors, and suicides. About nine months later, the agency said it had not reached a definitive conclusion about the matter, and its review would continue.

• A new drug treatment for fibromyalgia, milnacipran hydrochloride, has been approved by the FDA, the makers Forest Laboratories and Cypress Bioscience announced on January 14. Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor and has been tested in two large, phase 3 clinical trials involving more than 2,000 patients. Two other drugs, pregabalin and duloxetine, have already been approved for treating fibromyalgia.

Legal Briefs

• U.S. Sens. Herb Kohl (D-Wis.) and Charles Grassley (R-Iowa) have proposed new legislation to outlaw pharmaceutical companies' deals intended to keep generic drugs off the market, according to an announcement by Kohl's office on February 3. In recent years large pharmaceutical companies that market brand-name “blockbuster” drugs have entered settlements with generic drug makers over patent disputes. The results were that the generic manufacturers would delay the marketing of generic versions of these drugs while receiving multimillion-dollar payments or other types of business compensation from the brand-name makers. The Federal Trade Commission has been investigating and opposing these deals, but they have been approved by courts.

The proposed legislation, known as the Preserve Access to Affordable Generics Act, will prohibit such pay-off agreements between brand-name and generic drug makers. The bill is cosponsored by Sens. Russ Feingold (D-Wis.), Richard Durbin (D-Ill.), and Sherrod Brown (D-Ohio).

• In January Sens. Grassley and Kohl introduced a revised version of legislation they had proposed two years before that had sought to require public disclosure of industry gifts and payments to physicians. This Physician Payments Sunshine Act of 2009 has lowered the threshold of gift value for disclosure from $500 in the previous draft to $100. If passed, the bill will require all drug, device, and biologic manufacturers to report their gifts and payments to physicians, including travel and consulting fees, valued above $100. A searchable database would be established by the Department of Health and Human Services to post this information for public access.

The previous bill received support from several major pharmaceutical companies, such as Eli Lilly, which have begun or announced plans to begin posting payments and gifts to physicians on their company Web sites. The latest company to get on the bandwagon was Pfizer, which said in a February 9 announcement that it would publicly disclose all gifts and payments above $500 to physicians starting in 2010.

• On January 28 a U.S. district court judge in Florida dismissed two multimillion-dollar lawsuits against AstraZeneca alleging that its antipsychotic drug quetiapine fumarate caused harm, including diabetes and weight gain. These suits were brought by the first two of 15,000 plaintiffs who have filed lawsuits in the United States for similar claims regarding the drug. The judge ruled that the lawsuits did not meet the standards required for a case to proceed to trial.

• Eli Lilly has settled civil lawsuits and a criminal charge with the federal government and about 30 state governments over its antipsychotic drug olanzapine for a massive $1.42 billion, according to a January 15 Associated Press report. The company pleaded guilty to a misdemeanor violation for promoting the drug for off-label use in patients with dementia from September 1999 to March 2001. The civil lawsuits were related to overcharging state Medicaid programs.

Industry Briefs

• J&JPRD announced on February 6 that it filed a new drug application with the FDA for expanding the indication of paliperidone tablets to schizoaffective disorder. Paliperidone is currently approved for treating schizophrenia. The company is also seeking FDA approval for paliperidone palmitate, the long-acting injection formulation of paliperidone, for the treatment of schizophrenia.

• AstraZeneca has licensed a number of triple reuptake inhibitor molecules, discovered by Mayo Clinic and Virginia Tech Intellectual Properties Inc. scientists, that it hopes will lead to development of a new class of medication for depression treatment. According to a February 9 company announcement, these triple reuptake inhibitors are expected to interact with serotonin, norepinephrine, and dopamine receptors.

Currently available antidepressants affect the reuptake receptors of either serotonin or both serotonin and norepinephrine. The novel molecules will have to go through preclinical animal experiments before they can be tested in clinical trials.

• Supernus Pharmaceuticals announced on January 30 that it had begun a phase 2a clinical trial of SPN810, an investigational drug for the treatment of conduct disorder in pediatric patients with attention-deficit/hyperactivity disorder. It would be a randomized, open-label trial lasting six weeks.

• NPL-2008, a formulation of fluoxetine being tested for autistic disorder, disappointed in a phase 3 clinical trial, the company developing the drug, Neuropharm, announced on February 18. In this trial, 158 patients with autistic disorder aged 5 to 17 were treated with either NPL-2008 or placebo for 14 weeks, but the drug did not differ significantly from placebo in improving the symptom of repetitive behaviors. ▪