DID - Nov. 23, 2009 Issue

Vol. 8 No. 228

Early Meridia Data May Indicate Higher Cardiovascular Risk

Healthcare professionals should avoid prescribing Abbott Laboratories’ anti-obesity drug Meridia for patients with a history of cardiovascular events as preliminary data suggest patients taking the drug have a higher number of events including heart attack, stroke and death.

Abbott’s current labeling for the drug recommends that it not be prescribed for patients who have cardiovascular disease. According to preliminary results of a six-year study, 11.4 percent of patients taking Meridia (sibutramine) experienced cardiovascular events compared with 10 percent of patients taking a placebo, according to a recent FDA early communication.

The FDA alert is based on the SCOUT study that was intended to demonstrate the superiority of Meridia in reducing cardiovascular events associated with weight loss versus a placebo. About 10,000 patients age 55 years and older who were overweight or obese and had a history of heart disease or Type 2 diabetes plus one additional cardiovascular risk factor were enrolled in the study.

The preliminary findings highlight the importance of following the drug’s labeling, avoiding the use of sibutramine in patients with a history of coronary artery disease, congestive heart failure, arrhythmias or stroke, the FDA alert says. It also urges physicians to carefully evaluate the benefits and risks of the drug in individual patients and says consumers should ask their doctors whether Meridia is safe for them.

Meridia was approved by the FDA in 1997 and by the European Medicines Agency (EMEA) in 1999 under the brand Reductil. It is indicated for management of obesity in conjunction with a low-calorie diet. The SCOUT trial, initiated in 2002, is part of a postapproval commitment between Abbott and the EMEA.

“Sibutramine was not recommended in more than 90 percent of the patients in the SCOUT study,” Abbott spokesman Kurt Ebenhoch told DID, adding that the data safety board regularly reviewed the safety data over the course of the study to determine if the trial should continue. Abbott is “reviewing and evaluating the full body of data,” Ebenhoch added.

Ebenhoch also noted that patients in the study were treated with Meridia for substantially longer times than indicated in either the U.S. or Europe. In the U.S., Meridia is approved for treatment for as much as one year; the EU approved as much as two years of treatment.

The FDA’s review of the data is also ongoing and no conclusions are being made about the preliminary data, the agency says.
U.S. sales of Meridia in 2009 are expected to be about $40 million, Ebenhoch said. — Meg Bryant


GSK Withdraws sNDA for Avodart for Prostate Cancer

GlaxoSmithKline (GSK) is withdrawing its sNDA for Avodart (dutasteride) to reduce the risk of developing prostate cancer but plans to resubmit the application with revised data soon.

The data are not related to new findings on safety or efficacy but “should have been included” in the original filing, GSK spokesman Rob Perry told DID Monday. “We hope to take care of this and refile as soon as possible.”

The company filed the sNDA Oct. 1 and a separate supplemental application with the European Medicines Agency at about the same time, Perry said. Review of the EU filings will begin after the same update has been provided to the agency, GSK says in a statement.

Avodart is currently approved for the treatment of benign prostate enlargement. GSK reported global sales of Avodart of $212 million in the third quarter, according to its earnings report. — Meg Bryant


Pfizer Manufacturing Delays Cause Tikosyn Shortage

Manufacturing delays at Pfizer are expected to cause a shortage of the heart drug Tikosyn beginning in early December, the company says.

The shortage involves 60-count bottles of Tikosyn (dofetilide) 250 mcg and 500 mcg, the company says in a “dear healthcare provider” letter posted Monday on the FDA’s website for current drug shortages.

Pfizer is working as quickly as possible to resolve the situation, the letter says, noting the shortage is not the result of any efficacy or safety issues. No details about the delays were given in the letter.

Tikosyn is indicated for the maintenance of normal sinus rhythm in patients with atrial fibrillation/atrial flutter that lasts more than a week and who have been converted to normal sinus rhythm.

Pfizer is advising healthcare professionals to prescribe additional 125-mcg bottles for patients requiring the dosages affected by the shortage.

The company did not respond to a request for comment by press time. — April Hollis


Texas District Court Dismisses Vioxx Lawsuit Against Merck

Merck has been granted a motion for summary judgment dismissing all claims by the Texas state attorney general’s office, which sought a refund of Medicaid funds spent on the withdrawn painkiller Vioxx.

The Texas Attorney General’s office alleged Merck had violated the Texas Medicaid Fraud Prevention Act (TMFPA) by misrepresenting the safety of Vioxx (rofecoxib). The lawsuit sought to have the company refund all the money the state spent purchasing the drug or treating patients injured by it, Merck says in its most recent financial statement.

Judge Scott Jenkins in the 345th Judicial District Court of Travis County, Texas, ruled that TMFPA was not designed to apply to claims such as those brought by the state and that the state had failed to produce any evidence demonstrating that the company had caused the state damages.

“Evidence showed that the company acted responsibly and truthfully in its communications about Vioxx with the state of Texas, doctors in the state” and the FDA, the company says.

Jenkins sided with Merck in dismissing all of the state’s claims with prejudice and ruling that a trial of the claims was not necessary.

Jerry Strickland, communications director for the Office of the Attorney General on the Merck case, said in an emailed statement Monday, “The state will continue its efforts to recover taxpayer dollars that were unnecessarily spent. We are considering all options for review of this ruling at both the trial and appellate court level.”

The dismissal follows a ruling in June by the 14th Court of Appeals of Texas that Vioxx did not play a role in the death of a Texas man (DID, June 8). A three-judge panel of the appellate court reversed a lower state court ruling that Vioxx had caused Bob Ernst’s sudden cardiac death in 2001.

Merck also agreed in principle in August to pay $80 million to third-party payers, such as unions and health insurance plans, that paid all or part of the cost for Vioxx used by their plan members or people covered by their insurance (DID, Aug. 5).

The case dismissed by the District Court is The State of Texas v. Merck & Co., Inc. — David Belian


ARCA Gets Fast Track Status, Plans to Study Drug in One Genotype

ARCA Biopharma has received fast-track designation for its chronic heart failure drug Gencaro, for use in a patient population whose genotype appears to respond favorably to the pharmaceutical.

The company plans to submit a study protocol through the FDA’s special protocol assessment process to assess Gencaro’s (bucindolol HCl) safety and efficacy in the fourth quarter of this year and could begin the trial in late 2010 or the first half of 2011, ARCA says in a statement Monday.

ARCA anticipates the protocol will be a superiority comparison to AstraZeneca’s beta-blocker Toprol-XL (metoprolol succinate CR/XL), which is approved for heart failure and other indications, according to the statement. The study will enroll about 3,000 patients who have chronic heart failure and the chosen genotype.

The company expects the submission to propose a primary endpoint for the trial that measures cardiovascular hospitalization and mortality. If the FDA approves the protocol, the trial could reach the specified number of endpoint events as soon as two years after it begins, ARCA says.

Gencaro is a beta-blocker and mild vasodilator for treatment of chronic heart failure in genotype-defined heart failure patients. Earlier this year, ARCA received a complete response letter for the drug, according to a Nov. 16 statement from the company. — April Hollis


EMEA Advises Drugmakers on Using Postmarket Safety Reporting System

Drugmakers reporting adverse events to the European Medicines Agency (EMEA) should identify the country where the event occurred and the seriousness of the event to avoid receiving an error message from the agency’s electronic postmarket safety reporting system, the EMEA says in an updated EudraVigilance guidance.

The EMEA is updating and replacing its previous guidance on the system, “Note for Guidance — EudraVigilance Human Version 7.0 — Processing of Safety Messages and Individual Case Safety Reports,” to reflect more current experience.

EudraVigilance is a data processing network and management system used to report and evaluate suspected adverse reactions during clinical development and following the marketing authorization of medicinal products in the European Economic Area (EEA). The system started collecting reports in clinical trials in May 2004 and began requiring drugmakers to file their adverse events reports electronically in 2005 (DID, May 12, 2005).

Manufacturers using the system should provide the outcome of the adverse event, a description of the drug’s role in the event and the active ingredient of the drug, the EMEA says in the guidance, which applies to all individual case safety reports submitted to the system.

In addition to identifying the country and severity of the event, drugmakers also should provide the EMEA with a start and end date for the event and identify at least one drug or drug interaction that may have been responsible for its occurrence.

Other rules that users of the EudraVigilane system must follow include:

  • Any report from studies transmitted to the EudraVigilance system should identify whether the event occurred during individual patient use or during other studies;
  • The “test name” data element should be populated with a valid Medical Dictionary for Regulatory Activities (MedDRA) lower-level term (LLT) name or code;
  • Only numeric MedDRA LLT codes should be used in designated fields;
  • Values of age, weight and height should not be above 150 years, 650 kg and 250 cm, respectively; and
  • If the data element “pharmaceutical form (dosage form)” is populated, the value should match with the latest version of the European Pharmacopoeia Dosage Forms list.

The EMEA “Note for Guidance EudraVigilance Human Processing of Safety Messages and Individual Case Safety Reports” can be found at www.emea.europa.eu/pdfs/human/phv/2066504enfin.pdf. — David Belian



In the Nov. 20 issue of Drug Industry Daily, the story “FDA Clears Way for Use of Rituxan for Leukemia” said, “The FDA has approved Genentech and Biogen Idec’s Rituxan plus chemotherapy for patients with untreated chronic lymphocytic leukemia (CLL).” It should have read, “The FDA has sent Genentech and Biogen Idec a complete response letter regarding Rituxan plus chemotherapy to treat patients with untreated chronic lymphocytic leukemia (CLL).”

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