Relenza Prophylaxis Indication Withdrawn In EU; Pediatric Use Cleared In U.S.

Glaxo Wellcome's influenza medication Relenza for prevention of flu was withdrawn from the EU mutual recognition process so the company could resubmit the application with more data in elderly and high-risk patients, Glaxo said.

The trials are currently in the data collection and analysis stage and could not be appended to the prophylaxis application, which was submitted Nov. 5, the company said. Glaxo withdrew the application the week of May 22.

The trials are the same ones that will be submitted to U.K.' s National Institute for Clinical Excellence, in early autumn, to persuade NICE that Relenza (zanamivir) is cost-effective for flu treatment (¹ (Also see "Relenza Use In U.K. For 2000 Season Will Await Four Ongoing Glaxo Trials" - Pink Sheet, 11 Oct, 1999.)).

However, the company did not give a timeline for resubmission of the application for prophylaxis. Glaxo suggested that it might not even resubmit the application in the EU. A prophylaxis indication in the U.S. is on track for submission late in 2000, based on U.S. trials, Glaxo said.

The withdrawn EU application also included pediatric data for patients as young as five years old. In the U.S., pediatric data was submitted separate from the prophylaxis indication; a pediatric supplement was approved April 26 (² (Also see "Glaxo Wellcome Relenza" - Pink Sheet, 1 May, 2000.)).

However, the U.S. pediatric approval only extends to patients as young as seven years old. In the approval letter FDA said, "We note that you have submitted safety and efficacy information in children five years of age and older. However, the totality of evidence did not adequately support approval for children under age seven years."

FDA observed that patients under seven might not be able to use the Relenza inhalation device. The agency also asked Glaxo to provide more information on a nebulized formulation and its possible utility in younger pediatrics.

The supplement for children over seven did not meet all of the requirements of the pediatric written request issued for the drug, so an additional six months of exclusivity has not been awarded. The agency will determine at a later date whether the data are enough to satisfy FDA's pediatric study requirements, the approval letter indicates.

Glaxo is also in discussions with FDA regarding an upcoming letter to healthcare professionals regarding postmarketing events seen with Relenza.

Glaxo reported in April 1999 that 67% of patients were protected from contracting influenza after taking Relenza for 28 days, and 84% were protected against flu symptoms associated with fever.

In comparison, the injectable influenza vaccine, which is tailored to the anticipated flu strains for the upcoming season, is about 80% effective for preventing symptoms in its first use against a new strain, the U.K. Department of Health has determined.

In its influenza pandemic preparedness plan, DoH advocated development of a flu vaccine against the specific strain rather than use of a broad influenza antiviral drug for prophylaxis.

DoH noted that amantadine and rimantadine are about 70% effective for prophylaxis. These two drugs are older small-molecule flu drugs that work against influenza A but not influenza B.

Relenza, a neuraminidase inhibitor, is effective against both influenza A and B. Roche's Tamiflu (oseltamivir), another new neuraminidase inhibitor flu drug, was recently withdrawn from consideration in the EU because there was not enough evidence to support efficacy claims against influenza B (³ (Also see "Roche Proteomics Group Focusing On Ways To Diagnosis Alzheimer's Disease" - Pink Sheet, 29 May, 2000.)).

Amantadine is substantially less expensive than Relenza, but DoH only recommended its use in the case of a pandemic to healthcare workers when vaccine is not available or to patients in risk groups for whom the vaccine is contraindicated.

DoH announced a change in its flu immunization policy May 23, expanding the population of people who should be given the flu vaccine for prophylaxis. The recommendation now extends to all people over age 65 as well as at-risk populations.

The previous recommendation was for people over 75. DoH has set a goal of 70% uptake for all people over 65, with 60% uptake in the first year. The department estimates that 10 mil. doses of vaccine will be required this year, up from 7.8 mil. doses used in the U.K. for the 1999-2000 season.