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I first read about Lybrel in a Ubyssey article about a year ago, and again yesterday, on the NY Times website. This oral contraceptive pill meant to be taken 365 days a year is scheduled to be approved by the FDA next month.

In typical media fashion, the NY Times article focused on the (sexier?) issue of the attitudes of women (Anne Frank included, for some reason) towards menstruation and the lack thereof. Like many others, I take no issue with the concept of not ever getting a period. The same goal is achieved with other means of birth control such as the levonorgestrel-containing Mirena IUD, the injectable Depo-Provera containing medroxyprogesterone acetate, or the levonorgestrel-containing implant Norplant.

I do have a problem with the clever marketing by Wyeth Ayerst, because I believe Lybrel is not a novel idea nor a new medication. It is just that: a marketing ploy.

For the non-health professionals, a quick summary:

The various oral contraceptives available on the US/Canadian market contain different active ingredients. Some are mini-pills containing only a progestin (or progestogen) – generally these are less effective but are preferred by certain women who cannot tolerate estrogen-containing pills because of side effects (e.g. migraines) or for breastfeeding, etc. Other oral contraceptives contain a combination of an estrogen (usually ethinyl estradiol) and a progestin (different forms such as levonorgestrel, norgestimate, norethindrone, desogestrel, etc.). Some combination pills are monophasic, with the same composition throughout the cycle, and some triphasic, with varying amounts of the ingredients for each week of the cycle.

However, all “extended cycle” combination oral contraceptives (the Lybrel mentioned in the article, its close sister Alesse and the competitor Seasonale) contain the same 2 active ingredients: ethinyl estradiol and levonorgestrel

Seasonale

Seasonale is the in-between option: it is taken for 3 months straight, resulting in only 4 periods per year. It contains slightly higher doses of the hormones than either Alesse or Lybrel.

Alesse

Alesse is an already-popular traditional low dose pill marketed by Wyeth. However, Alesse is not currently FDA-approved for taking continuously as a contraceptive – you have to take a 7 day break every cycle in order to get a ‘fake’ period which has no biological purpose at all and was another marketing ploy. Many Alesse-takers* (some on the advice of their physicians for conditions such as dysmenorrhea or endometriosis, and some for the convenience factor) take the pills continuously with no breaks, and with no significant increase in side effects.

Lybrel

Lybrel is basically Alesse, albeit with 10% less levonorgestrel. None of the 4 studies Wyeth presented in support of its New Drug Application to the FDA showed any physiological reason for lowering the levonorgestrel dose. Thinking (hard) back to my pharmacy classes, the only hypothesis I can raise is that the lower levonorgestrel dose makes Lybrel less likely than Alesse, and certainly than Seasonale, to have certain side effects: androgenic side effects like acne and effects on carbohydrate metabolism including increased insulin resistance. I doubt the possible increase in these side effects was the concern, since the standard levonorgestrel dose on the market is between 100 and 150 mcg currently, and other manufacturers would have jumped on the bandwagon sooner. However, the 4 studies released by Wyeth focused on other issues and showed:

• successful inhibition of ovulation in 37 patients taking Lybrel, and resumption of ovulation on stopping it – a 6 month phase II study
• safety (side effects) and pregnancy prevention in 2,134 patients were similar to other approved cyclic oral contraceptives (but only 43% of these patients completed the study, with only 58% of those reporting a bleeding-free cycle during the final month, and 19 of them became pregnant) – a 1 year phase III study
• decrease in endometrial thickness in 93 patients – a 1 year phase III study
• reduction in PMS-related symptoms in 114 patients – a 1 year phase III study

Last year, Wyeth released two additional studies in response to the FDA’s request:

• return to menstruation or pregnancy within 90 days of discontinuing Lybrel in 99% of the 187 study subjects who took it for 1 year continuously
• a 1 year comparative study with Alesse, showing similar side effects but more spotting with Lybrel, with none of the 323 women taking Lybrel getting pregnant while 3 of the 318 taking Alesse did

Perhaps getting FDA approval to extend the indications for Alesse was more expensive than marketing a whole new brand? Or perhaps Wyeth thought it would be just too confusing to explain that Alesse can be taken in different ways? Or maye it’s just more profitable to market what is almost the same medication to different groups of potential customers? It certainly makes a bigger splash to talk about a “new” birth control pill, than to quietly add another indication to an existing one. Wyeth is probably counting on Lybrel to steal some of Seasonale’s $120million in annual sales, plus some of the sales of the other menstruation-suppressing contraceptives. What do you think?
*including this one.

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