|
Research Triangle Park, N.C., June 7, 2002 - Today the U.S. Food and Drug Administration (FDA) approved the Supplemental New Drug Application (sNDA) for Lotronex® (alosetron hydrochloride) Tablets which provides for the re-introduction of the medicine to the marketplace under restricted conditions of use.
Lotronex Tablets will be indicated specifically for use in women with severe diarrhea-predominant irritable bowel syndrome who have failed to respond to conventional therapy, whose IBS symptoms are chronic and who have had other gastrointestinal medical conditions that could explain their symptoms ruled out. Symptoms that make diarrhea-predominant IBS severe are frequent and serious abdominal pain, fecal incontinence or the uncontrolled urge to have a bowel movement, or curtailment of daily activities because of IBS.
Serious gastrointestinal events, specifically ischemic colitis and complications of constipation, have been reported in association with the use of Lotronex. These events have resulted in hospitalization, blood transfusion and/or surgery and some fatalities. In clinical trials, about three women in 1,000 developed ischemic colitis over six months.
Lotronex was voluntarily withdrawn by GSK in November 2000 when the company and the FDA were unable to agree on a Risk Management Plan that would guide appropriate use of Lotronex without presenting undue obstacles to patients. However, GSK and the FDA resumed discussions in January 2001, after thousands of patients who had successfully used Lotronex implored both the company and the Agency to work out a plan that would allow them access to Lotronex. These discussions culminated with the submission of the Supplemental Application. The return of a drug that was voluntarily withdrawn from the market is virtually unprecedented.
The approval comes six weeks after a joint FDA advisory panel of members of the GI Drugs Advisory Committee and the Drug Safety and Risk Management Subcommittee recommended that the FDA consider re-introduction of Lotronex under marketing restrictions. The committee requested that the Agency and company develop a plan to achieve this goal.
"We are pleased with the significant efforts that both we and the FDA put into finding a resolution," said Peter Traber, M.D. Senior Vice President and Chief Medical Officer at GlaxoSmithKline. "We and the FDA always had the same goal during our discussions - to provide an effective medicine to appropriate patients. We are pleased to have been able to work out a risk management plan that will allow the most severely affected IBS patients access to Lotronex. .
"Clearly, the beneficiaries from today's announcement are the patients who will benefit from Lotronex." Dr. Traber said. "The patients who wrote letters and e-mails, made phone calls and especially those who came in person to provide compelling and impassioned testimony at the advisory committee meeting deserve a great deal of credit for getting GSK and the FDA to resolve all of the issues leading to the reintroduction of this product."
GSK is working now to resume manufacture of Lotronex and to finalize details of how the risk management plan will be implemented. In addition, with the risk management framework now in place, GSK will develop the supporting physician and pharmacist-directed educational materials.
"We intend to make the product available as soon as we can finalize the components of the risk management plan, including approval of materials by the FDA, and complete the steps required for manufacturing," Traber said.
Risk Management Plan
The risk management plan approved today by the FDA includes, among other elements:
- Updated warnings in product labeling, including a Medication Guide for patients that explains to patients what to do if they get constipated or have signs of ischemic colitis.
- A lower starting dose than previously approved.
- A prescribing program for physicians to be enrolled into, based on self-attestation of qualifications and acceptance of certain responsibilities in prescribing the medicine.
- An agreement for patients to sign, attesting that they are informed about risks and benefits of Lotronex and agree to follow directions that are elements of the plan.
- Stickers affixed on all prescriptions for Lotronex to alert pharmacists that the prescribing physician is enrolled in the Prescribing Program for Lotronex (PPL).
- Directions to prescribers for active follow-up and management of patients.
- Measures to actively monitor and evaluate the plan.
Continued studies
GSK has committed to post-marketing (Phase IV) studies that would evaluate the safety and efficacy of lower doses of Lotronex and of taking Lotronex on an "as needed" basis. GSK will also conduct further studies to investigate the etiology of ischemic colitis and small bowel ischemia. In addition, the company will monitor the risk management program.
Irritable bowel syndrome is a chronic, recurring condition that affects an estimated 18.5 million Americans, approximately 67% (12.4 M) of whom are women. Although the cause is unknown, IBS is characterized by multiple symptoms that include chronic or recurrent abdominal pain and discomfort and irregular bowel function, such as diarrhea, constipation or alternating diarrhea and constipation. Approximately 30% of women with IBS have diarrhea-predominant IBS (3.7 million). Lotronex is indicated for women with severe diarrhea predominant IBS and the severe form of IBS is thought to affect up to 5% of this population.
Background on Lotronex
Lotronex received FDA approval for marketing in the U.S. on February 9, 2000. On November 28, 2000, after extensive discussion with the FDA, GlaxoSmithKline voluntarily withdrew Lotronex from the U.S. market.
In December 2001, GSK filed a supplemental application seeking FDA approval to allow the reintroduction of Lotronex tablets, under modified conditions of use and with restrictions imposed by a risk management plan, for women with diarrhea-predominant IBS who have failed with other therapy.
London-based GlaxoSmithKline, with U.S. headquarters in Research Triangle Park, N.C., and Philadelphia, is one of the world's leading research-based pharmaceutical and healthcare companies.
Complete Product Information
| Enquiries |
| US Media |
Ramona DuBose
|
(919) 483 2839
|
|
