4-periods-a-year pill eyed for use in U.S.
For years, providers have counseled women who are about to go on vacation or a honeymoon that periods can be delayed by omitting the "pill-free" week and continuing their daily dose of OCs. While this idea is not new, it has not been patented — until now.
Barr Laboratories of Pomona, NY, has signed an exclusive rights agreement with Eastern Virginia Medical School of Norfolk to develop and market a four-periods-a-year pill as a unique oral contraceptive. Researchers at the school’s Jones Insti tute for Reproductive Medicine, which patented the 84-day dosing regimen, will help devise the clinical trials necessary for Food and Drug Administration (FDA) approval of the product, now known as Seasonale.
Scientists are examining the actual hormonal components that will make up this monophasic pill, while others are organizing the summary of the clinical protocol that will be presented to the FDA, says Bruce Downey, Barr’s chairman and chief executive officer. The goal is to begin patient recruitment and establish clinical trials before the end of the year, Downey says.
By sticking with estrogen and progestin components previously approved by the FDA, research ers will be working with known compounds having already-established safety and efficacy profiles. While a final decision has not yet been reached, ethinyl estradiol and levonorgestrel may compose the basis for the Seasonale pill, says Gary Hodgen, PhD, professor of OB/GYN at Eastern Virginia Medical School and chair of the Jones Institute of Reproductive Medicine. "There could be other progestins put in," he comments. "We may try this at different doses, so that we find which dose will give us the most satisfactory breakthrough bleeding profile."
In staying with an established estrogen and progestin, the product can move faster through the research pipeline. If the 84-day dosing regimen proves safe, effective, and acceptable, the product may be on U.S. pharmacy market shelves by late 2002 or 2003, Bar says.
Family planners may not be familiar with Barr Laboratories’ name, but they already know one of its products. Barr manufactures the ethinyl estradiol/levonorgestrel pill used in the Preven Emergency Contraceptive Kit distributed by Gynétics of Somerville, NJ. The company also is collaborating with Gynétics to produce a progestin-only emergency contraceptive pill. (For more information on Gynétics’ initiation of advanced clinical trials on the progestin-only ECP, see Contraceptive Technology Update, March 1999, p. 28.)
Barr’s strength in the pharmaceutical business lies in its production of generic products. It markets generic versions of four hormonal agents used in women’s health care: danazol, medroxyprogesterone acetate, estradiol, and estropipate. It also successfully challenged and won the right to produce the generic form of tamoxifen. Barr is now in court to challenge the patents protecting Ortho-Novum 7/7/7, produced by Ortho Pharmaceutical Corp. in Raritan, NJ.
Barr began some three years ago to broaden its generic base of women’s health care drugs and establish its own proprietary products, says Downey. The collaboration with Gynétics in developing the Preven ECP kit represents the first of Barr’s proprietary products. Through its partnership with East Virginia Medical School, Barr now looks to bring another new and innovative OC product to market as a proprietary drug.
Why seek approval of a regimen providers already use? As with the Preven Emergency Contraceptive Kit, Seasonale will give providers a dedicated product with established, approved labeling, says Downey. Patients will benefit from clear package instructions and a design that promotes ease of pill-taking. Without established labeling and packaging, the margin for error increases, Hodgen says.
"The consequences of being wrong are great," he observes. "A [poorly] timed pregnancy can be a significant problem."
Benefits, drawbacks
Breaking the barriers of the 21/7-day dosing regimen has been examined informally by many in the reproductive health field. (For details, see box at left.)
One benefit of an extended pill cycle is that it places the patient in a very low estrogenic state and prevents menstruation, notes Rafael Haciski, MD, FACOG, director of Gynecology & Infertility Associates in Baltimore. Suitable candidates for this type of regimen include patients with endo metriosis who aren’t ready to conceive but would benefit from suppression and can’t take or afford gonadotropin hormone-releasing hormone analogue suppression therapy.
By maintaining a hypoestrogenic state, there would be little, if any, stimulation of the endome trio tic sites, thus keeping the condition in check, Haciski says. With no menstruation, irritation at the sites of endometriotic tissue would be lessened, thus minimizing damage and scarring.
"With such low doses of estrogen, I doubt that there would be any build up of tissue — more atrophy than not," observes Joseph Cutchin, MD, FACOG, founder of Peninsula Obstetrics and Gynecology, PA in Salisbury, MD. "In a person later desiring pregnancy, the question is, how long can you suppress the ovary without permanent damage?"
Hodgen says, "I think the answer to that is that we have no idea how long, but we have no evidence that suppressing ovulation has any effect on the age of menopause." In addition, Hodgen says, OCs can prevent ovarian and endometrial cancer, decrease the risk of benign breast disease, prevent atherogenesis, and offer host of other health benefits.
"On that basis, I think there is no reason at all to have any fears for using OCs for years to control one’s reproductive status," he notes. "There is no reason to suppose that it has any untoward effect on ovarian physiology."
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