DID - Aug. 24, 2009 Issue

Vol. 8 No. 164

Rx-360 Receives Mixed Reviews on Plan to Share Drug Industry Audits

The drug industry is expressing some skepticism about relying on an Rx-360 Consortium plan to conduct and share supply-chain audits, as the months-old consortium sets up working groups toward that end.

“It’s important that industry understand what they’re getting and verify the information,” Steven Niedelman, senior consultant with Crowell & Moring, told DID at the FDAnews Supplier Quality Management Congress Friday. “I think the program would be very efficient.”

Rx-360, which launched in June, was formed to ensure supply-chain security and share audit data among industry companies (DID, June 8). Suppliers would be chosen for audits based on member input, and members can view audit results on a subscription basis.

The industry may have a gut reaction against shared audits, particularly after the tainted heparin incident, Jackie Torfin, director of quality for Arizant Healthcare, told DID (DID, March 6). “My guess is people will be slow to adopt until they see some of the bigger players take the lead,” said Torfin, who also has worked for drugmakers.

Torfin added that companies may become more comfortable as they start viewing supplier audits as just one piece of assessing the supply chain, and as they gain a greater understanding of where their products are coming from.

But Gerard Pearce, executive vice president of SQA Services and a representative of the consortium, said at the conference that the group can’t guarantee the FDA will accept results of the audits. Also, suppliers can choose not to make audits results available, and conference participants pointed out they may do so if the results are unfavorable.

The database will contain sensitive information, so suppliers must grant permission for each member that wants to view the audit results.

There may also be financial challenges, as business insurance companies might consider raising premiums if companies are relying on third parties for their supplier audits, Joel Grosser, vide president of Procurement Consulting told DID.

Rx-360 probably will charge members about $10,000 annually to conduct supplier audits, Pearce said, pointing out it is a fraction of the cost of conducting audits individually.

Companies that are undecided may want to ask for a sample redacted audit report before committing to join the consortium, John Avellant, managing director and principal consultant for Cerulean Associates, suggested.

Rx-360 has eight working groups hammering out details on audit criteria and auditor qualifications, Pearce said. The working groups include Audit Standards, Audit Process, Auditor Qualification, Audit Database, Membership, Regulatory Liaison, Surveillance and Rx-360 Quality Management System. The group will hold board elections in December, Pearce said.

However, drugmakers may be hurting themselves if they are waiting for Rx-360 to solve their supplier audit shortcomings. “Some folks are going to get caught short with too many audits to do,” he said. — April Hollis


Lilly to Pay West Virginia $22.5 Million in Zyprexa Suit

West Virginia will receive $22.5 million from Eli Lilly to settle a lawsuit related to the alleged illegal marketing and promotion of the antipsychotic Zyprexa.

Lilly, which has denied all allegations of wrongdoing, has agreed not to make any written or oral claim that is false, misleading or deceptive about Zyprexa (olanzapine) or promote the product for off-label uses, as part of the consent judgment that was unsealed recently.

The state, whose case was part of the multidistrict litigation in the U.S. District Court for the Eastern District of New York, will receive $14.75 million to fund behavioral and mental health services. Attorneys representing the state will be awarded $6.75 million, and another $1 million will be placed in the consumer protection fund for state Attorney General Darrell McGraw’s office, according to the consent judgment.

The company said last month that it was in advanced discussions with the attorneys general for several states that were not part of the U.S. District Court for the Eastern District of Pennsylvania settlement, seeking to resolve their Zyprexa-related marketing claims.

Lilly reported a special pretax expense of $105 million in the second quarter, representing the estimated amount related to the states’ claims, according to a July 22 statement. During the first half the year, Zyprexa had sales of about $2.33 billion, according to Lilly.

Related cases brought by the attorneys general of Idaho, Mississippi and Louisiana are pending in the New York court, where In re: Zyprexa Products Liability Litigation is being heard.

Judge Jack Weinstein, who is hearing the case, urged all parties with pending cases involving Zyprexa marketing to settle, as “further delays will unnecessarily increase transactional costs.” — Elizabeth Jones


Second Clinical Trial Request for Medicines Company’s Oritavancin

The Medicines Company has been asked by the European Medicines Agency to conduct another clinical trial for its Targanta antibiotic, after a similar request was made last December by the FDA.

Medicines has withdrawn its European marketing authorization application (MAA) for oritavancin, an antibiotic intended for complicated skin and skin structure infections (cSSSI) caused by gram-positive pathogens, the company says in a statement Friday.

The MAA for a 200-mg, three-to-seven-day daily dose of the drug was filed in June 2008 by Targanta Therapeutics, which was acquired by Medicines in February. The drug is intended to treat such pathogens as methicillin-resistant Staphylococcus aureus, according to the company.

The FDA told Targanta in a December 2008 complete response letter that it would require a new clinical trial (DID, Dec. 10, 2008).

“The Medicines Company is in dialogue with the FDA regarding plans for a global Phase III program,” the company says in the statement, adding that it intends to confer with the European regulators as well to see if they support the program design.

The company expects to start the new clinical trials before the end of this year and thinks patient enrollment will take one or two years. It is now developing an intravenous formulation of oritavancin for cSSSI and in the future, possibly for anthrax, bacteremia and surgical prophylaxis. An oral formulation for Clostridium difficile, a pathogen that spreads in hospitals, is also under development.

The company did not respond to a request for comment by press time. — Martin Berman-Gorvine


Health Canada Requires Labeling Changes for TNF Blockers

Drugmakers marketing tumor necrosis factor (TNF) blockers in Canada are being required to update the products’ labeling to reflect an increased risk of cancer in children and young adults, less than a month after a similar FDA action.

The FDA is requiring manufacturers of TNF blockers to add a boxed warning identifying the increased cancer risk associated with use of the drugs in children and young adults (DID, Aug. 5).

Health Canada says in a statement last week that patients on TNF blockers, which are used to treat chronic inflammatory diseases, are at risk of developing certain types of cancers including lymphoma and the first appearance of the skin disorder psoriasis.

While the labeling for all TNF blockers in Canada already includes warnings and precautions on the risk of lymphomas and other cancers associated with the drugs, the updated labeling will highlight the risk of specific cancers, in particular information related to the occurrence of leukemia, Sharon Godsell, a spokeswoman for Health Canada, told DID.

The complete details of the labeling changes have not been finalized, but are expected to be completed in the fall or winter, Godsell said.

The agency recommends that patients already taking the drugs should not discontinue treatment without first speaking to their doctor.

There are currently five prescription TNF blockers authorized in Canada according to the statement:

  • Abbott Laboratories’ Humira (adalimumab);
  • Amgen and Wyeth’s Enbrel (etancercept);
  • Centocor Ortho Biotech’s Remicade (infliximab) and Simponi (golimumab); and
  • UCB’s Cimzia (certolizumab pegol). — David Belian


Gentium’s Liver Disease Drug Falls Short in Trial

Italian drugmaker Gentium’s liver disease treatment defibrotide has failed to meet efficacy endpoints in a Phase III trial, the company says.

The drug — designed to treat severe veno-occlusive disease in stem cell transplant (SCT) patients who received hematopoietic, or blood-forming, stem cells — did not meet the primary endpoint of the trial, the company says in a statement last week. Veno-occlusive disease is a potentially life-threatening condition and a common complication of SCT, the company says.

Despite the failure to meet the primary endpoint, Gary Gemignani, Gentium’s executive vice president and chief financial officer, told DID the trial’s results were compelling and did not rule out pursuing regulatory approval of the drug.

“The results place us in a strong position to continue discussions with the FDA and others regarding next steps toward a regulatory filing,” Gemignani says in a statement.

The primary endpoint was a complete response at 100 days following SCT, and the secondary endpoints were survival rates at 100 days and six months after SCT, Gentium says in the statement. The trial enrolled 102 patients for treatment with defibrotide.

Twenty-four percent achieved complete response at 100 days, Gentium says. For the secondary endpoints, 38 percent of the patients demonstrated survival at 100 days. Neither outcome reached the level of significance required to prove efficacy, the company says. — David Belian


Allergan Receives DDMAC Letter for Aczone

The FDA’s Division of Drug Marketing, Advertising and Communications (DDMAC) has sent Allergan a warning letter concerning an advertisement for the acne drug Aczone that overstated efficacy and omitted important risk information.

The letter says an advertisement for Aczone (dapsone) gel, 5 percent, is false or misleading. The advertisement also “omits material facts and important risk information associated with the use of the product,” according to the Aug. 17 letter posted to the FDA website Aug. 21.

The journal advertisement claims Aczone reduces inflammatory lesions by 24 percent in two weeks. However, the mean percent change in the number of inflammatory lesions in patients receiving a placebo was 22 percent during the same period, “which was not even nominally statistically significant,” according to the letter.

The letter also says the journal advertisement “grossly overstates” Aczone’s efficacy by offering only the most favorable result for the product and ignoring the placebo response. The advertisement says the Aczone users experienced a 48 percent reduction in inflammatory lesions at 12 weeks. However, a placebo group in a study had a 42 percent reduction at week 12, the letter states.

Allergan’s advertisement also failed to include information on potential drug interactions. Specifically, the advertisement failed to warn that topical application of Aczone followed by use of benzoyl peroxide could result in temporary local yellow or orange discoloration of the skin and facial hair with resolution in 4 to 57 days.

DDMAC asks Allergan to cease the dissemination of the promotional materials. The agency also asks for a written response to the letter by Aug. 28 indicating whether the company will comply with the request and identifying steps it will take to discontinue the use of the violative materials, according to the letter.

“We received the letter from the FDA this week,” Cathy Taylor, a spokeswoman for Allegan, told DID Aug. 21. “We are working closely with the FDA to address its issues/concerns regarding the ad.”

The advertisement is no longer in use and last appeared in May in physician-focused publications, Taylor added. — Elizabeth Jones


Galderma Gets DDMAC Warning Letter for Visual Aids

Galderma Laboratories received an FDA warning letter that says the company overstated the efficacy of its Tri-Luma cream for the skin condition melasma in visual aids and minimized important risks.

The agency’s Division of Drug Marketing, Advertising and Communications (DDMAC) reviewed two professional visual aids for Tri-Luma (fluocinolone acetonide/hydroquinone/tretinoin), which is indicated for the treatment of moderate-to-severe melasma, or hyperpigmentation, of the face when a patient is taking measures to avoid sun exposure and use sunscreens, the warning letter dated Aug. 18 and posted to the FDA’s website Aug. 21 says.

The visual aids were disseminated with unapproved product labeling that also included false and misleading claims about the product, according to the letter.

Tri-Luma was approved Jan. 18, 2002, for short-term treatment of melasma. One of the visual aids suggests that it is safe for long-term use, the letter says.

For example, the visual aids suggested that Tri-Luma is safe and effective for use in combination with glycolic acid peels, DDMAC says. The drug’s approved prescribing information warns that Tri-Luma should not be used with other keratolytic drugs such as glycolic acid, the agency says.

The aids downplay risks such as adrenal function suppression and omit information about the consequences of that effect and the consequences of discontinuing treatment, according to the letter.

DDMAC requests that Galderma immediately stop disseminating the promotional materials cited in the letter. It gives the company until Aug. 31 to indicate whether it plans to comply with the request and to explain how it will discontinue the use of all violative promotional materials.

Galderma did not respond by press time to a request for comment. — David Belian


Customer Service: Kim Williams
(888) 838-5578 • +1 (703) 538-7600
Editorial: David Grant
(703) 538-7600
Ad Sales: Matt Salt
(703) 538-7642
Content Sales: Alka Desai
(703) 538-7669

300 N. Washington St., Suite 200 • Falls Church, VA 22046-3431
Phone: (888) 838-5578 • +1 (703) 538-7600 • Fax: +1 (703) 538-7676

Reporters: David Belian, Martin Berman-Gorvine, April Hollis, Elizabeth Jones

President: Cynthia Carter; Publisher: Matt Salt; Editorial Director: David Grant; Executive Editor: Theresa Barry

Copyright © 2009 by Washington Business Information Inc. All rights reserved. Drug Industry Daily (ISSN 1541-6607), an executive briefing on the regulation of pharmaceuticals, is published daily, 250 issues, for $1,495. Photocopying or reproducing in any form, including electronic or facsimile transmission, scanning or electronic storage is a violation of federal copyright law and is strictly prohibited without the publisher’s express written permission. Subscribers registered with the Copyright Clearance Center (CCC) may reproduce articles for internal use only. For more information, contact CCC at www.copyright.com or call (978) 750-8400. For site licenses for multiple users or to purchase multiple copies, contact Content Sales Manager Alka Desai at (703) 538-7669.