MGI PHARMA SALAGEN sNDA FOR SJOGREN's SYMPTOMS TO BE FILED BY EARLY 1997; FDA AGREES TO DISSEMINATION OF ABSTRACT ON EARLY USE OF SALAGEN WITH RADIATION

MGI Pharma is planning to submit a supplemental NDA for Salagen (pilocarpine tablets) for the treatment of dry mouth and dry eyes associated with Sjogren's syndrome "before the end of 1996 or very early in 1997," the company said.

Salagen is approved for salivary gland hypofunction caused by radiation used in the treatment of head and neck cancer. A 629-patient Phase III study of Salagen 5 mg taken four times daily concluded that the drug is significantly better than placebo in relief of Sjogren's symptoms, the company announced Nov. 19. Benefit was seen at six and 12 weeks, and "the primary adverse event was sweating," the company said. In a Phase III maintenance study, patients on Salagen continued to "experience relief for their oral dryness and discomfort for over a 12-month period with no reduction of benefit," the company said. MGI committed to finish the evaluation of Salagen for Sjogren's syndrome when the initial NDA was approved in late March 1994 ("The Pink Sheet" March 28, 1994, T&G-8).

MGI's reference to the use of Salagen for Sjogren's patients was the subject of an exchange of letters with FDA's Division of Drug Marketing, Advertising & Communications.

In March, DDMAC wrote to MGI asking why the company included a health care provider letter containing data on Salagen's use in the treatment of dry mouth in Sjogren's syndrome among promotional materials submitted to DDMAC for review. The letter stated that MGI is studying the drug in Sjogren's at 29 sites, and included abstracts and journal reprints on the use. FDA pointed out that "dissemination of these materials would be considered the promotion of an unapproved use for Salagen unless these materials are disseminated in response to an unsolicited request directed or referred to the medical affairs personnel at MGI."

MGI responded that the letters "were filed by mistake." The provider letter was prepared because "some investigators have submitted abstracts to report their findings" on use of Salagen for Sjogren's syndrome, and "MGI suspects that such reports may trigger unsolicited requests from healthcare providers regarding the use of Salagen tablets in patients with Sjogren's," the company explained.

"To ensure that no violation of FDA rules relating to off-label use of Salagen tablets occurred, MGI instituted more stringent internal review procedures to review medical communications' letters. The letters were mistakenly submitted because of this more stringent review process," MGI maintained. On May 22, FDA responded that it "accepts MGI's explanation of the issue and considers the matter closed. DDMAC acknowledges MGI's cooperation in this matter."

Separately, MGI convinced FDA to allow the company to distribute an abstract regarding immediate use of Salagen during head and neck radiation.

The abstract, "Salivary Gland Sheltering Using Concurrent Pilocarpine," was published in the March American Journal of Clinical Oncology. In a May 6 letter, FDA objected to dissemination of the abstract, claiming it involved an off-label use of Salagen for prevention of dry mouth. DDMAC distinguished the approved indication, the alleviation of dry mouth and dry eye due to head and neck cancer radiation, from the prevention of such symptoms, which it considered an unapproved use.

In a May 13 response, MGI said it would halt dissemination of the abstract pending a resolution of the issue, but argued that the use of Salagen in the study falls under the approved indication. MGI maintained that dry mouth symptoms appear "promptly with the initiation of radiation therapy" and that it was reporting "on the immediate treatment of these symptoms" for alleviation, not prevention, of dry mouth symptoms. "By reducing the early symptoms," MGI said, the study found "that no patient...had to discontinue radiation therapy." MGI's purpose for disseminating the abstract was to provide "confirming information to physicians that patients benefit from early treatment of symptoms of xerostomia and not waiting until all symptoms have fully manifested," the company maintained.