DID - Jan. 12, 2009 Issue

Vol. 8 No. 6

International GMP Inspection Partnership Begins

The FDA, the European Medicines Agency (EMEA) and Australia’s Therapeutic Goods Agency (TGA) have begun an 18-month pilot project to collaborate on good manufacturing practice (GMP) inspections.

The three agencies kicked off the project with a teleconference to discuss specific actions they will take, including coordinating inspections of manufacturing sites that have come to the attention of more than one of the agencies, the EMEA says in a statement Friday.

When the pilot phase concludes in June 2010, the agencies will analyze achievements and make recommendations for future action, including possible expansion of the program.

The agencies have agreed to:

  • Make GMP inspections more transparent and visible;
  • Decrease the number of duplicate inspections;
  • Increase the number of pre- and postapproval inspections of sites that produce active pharmaceutical ingredients;
  • Increase the number of inspections that are useful to more than one agency; and
  • Continually assess performance.

The agencies will measure these performance indicators against data collected from 2006–2008, the EMEA says. The pilot project document is available at
www.emea.europa.eu/Inspections/docs/43043807enrev1.pdf — Martin Gidron


FDA Requests More Data for Additional Gardasil Indication

The FDA has issued a second complete response letter to Merck on a new indication for Gardasil — to prevent infection of women age 27–45 with the virus that causes cervical cancer.

The agency has recommended that the company submit additional data when a 48-month study has been completed. Preliminary results were presented at a Beijing conference November 2007.

Merck anticipates providing a response to the agency in the fourth quarter, according to a company statement Friday. 

Gardasil is indicated for use in girls and young women age 9–26 years for the prevention of cervical, vulvar and vaginal cancers caused by HPV types 16 and 18, genital warts caused by HPV types 6 and 11 and precancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18.

The first complete response letter on the new indication pointed to issues that precluded approval within the six-month priority review period the FDA granted last March (DID, March 20, 2008). The initial sBLA included data collected for an average of 24 months into the study, which is when the number of prespecified endpoints had been met. 

The second complete response letter followed the FDA review of Merck’s response last July to the first letter. 

Gardasil Sales

Last month, the drugmaker predicted Gardasil 2009 sales will be $1.4 billion to $1.6 billion (DID, Dec. 5, 2008).  The company will report its fourth-quarter and 2008 sales Feb. 3.

Gardasil was approved by the FDA for the prevention of vulvar and vaginal cancer last September, expanding the indication from cervical cancer prevention alone (DID, Sept. 15, 2008).

The drugmaker submitted an sBLA last month to add use of the vaccine in males age 9–26 to prevent men and boys from transmitting the infection to females through sexual contact (DID, Jan. 9). — Elizabeth Jones


Solzira NDA for Restless Legs Syndrome Is Refiled

GlaxoSmithKline (GSK) resubmitted its NDA Friday for Solzira, a treatment for moderate-to-severe restless legs syndrome.

The application was withdrawn last year after the FDA requested data from one study be reformatted (DID, Nov. 11, 2008). GSK conducted an additional review of other clinical studies based on the feedback it received from the agency, the company says in a statement Friday. The new FDA action date is Nov. 9.

GSK licensed Solzira (gabapentin enacarbil) extended-release capsules from XenoPort in 2007. The product is a new chemical entity, reformulated to improve the pharmacokinetics of gabapentin, both the companies say.

The drug could replace GSK’s restless leg syndrome treatment Requip (ropinirole HCl), which started facing generic competition last year and had sales of $676 million in 2007 (DID, May 21, 2008).

The drug is also in Phase II testing for the prevention of migraines and the treatment of neuropathic pain. — Christopher Hollis


Study Criticizes Use of Antipsychotics in Alzheimer’s Patients

The use of antipsychotics in patients with Alzheimer’s disease increases the long-term mortality risk, a study shows.

“These results further highlight the need to seek less harmful alternatives for the long-term treatment of neuropsychiatric symptoms in these patients,” lead researcher Clive Ballard, a professor at King’s College in London, said last week in the online edition of The Lancet Neurology.

The study was a randomized, placebo-controlled treatment discontinuation trial of 165 Alzheimer’s disease patients who lived in UK healthcare facilities. Patients were randomized to either stop or continue treatment with antipsychotic medication for 12 months. Researchers followed up on patients by telephone after two years. 

The drugs patients received include thioridazine, chlorpromazine, haloperidol, trifluoperazine and risperidone. The cumulative probability of survival for patients on treatment was 70 percent at 12 months compared with 77 percent for the placebo group. The differences were greater at 24 months, when the probability of survival was 46 percent for patients taking antipsychotics compared with 71 percent for those on placebo, according to the study.

Last year, the FDA requested that warnings citing an increased risk of death in patients with dementia taking atypical antipsychotics be expanded to include older conventional antipsychotics (DID, July 17, 2008). — Christopher Hollis


Zingo Gets Additional Pain Indication

The FDA has approved an sNDA to expand the indications for Anesiva’s Zingo pain drug about two months after the company said it would halt commercial activities related to the product.

Anesiva is seeking to license its Zingo (lidocaine HCl) powder intradermal injection system to a third party, along with the underlying drug delivery technology and intellectual property rights.

Zingo, Anesiva’s first product, was approved to treat the pain associated with inserting peripheral IVs and getting blood samples from children age 3–18. The new indication is to treat the pain associated with taking blood samples in adults.

Last November, Anesiva recalled Zingo due to a potential shelf-life issue from a lot of unreleased product, according to a “dear healthcare professional” letter dated Nov. 11.  No safety problem was involved in the recall. The company subsequently said it would stop commercial activities related to the product.

Anesiva is focusing on the development of Adlea, its novel formulation of capsaicin for the management of acute pain following orthopedic surgeries, according to a company statement. — Elizabeth Jones


Customer Service: Carmen Park
(888) 838-5578 • +1 (703) 538-7600
Editorial: David Grant
(703) 538-7600
Ad Sales: Andrew McSherry
(703) 538-7643
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: Martin Gidron, Christopher 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.