Obesity Musings On Alkermes, J&J News

I am always on the lookout for news in the obesity drug area. But lately two of the molecular components of experimental obesity drugs in late-stage clinical trials-naltrexone and topiramate- are in the news for other reasons.

Alkermes announced this morning that it will receive priority review from FDA for VIVITROL, an injectable extended-release formulation of naltrexone, for treating opioid-dependent patients, with a PDUFA date of October 12, 2010. The idea is that a once-monthly injection of VIVITROL would be given to lower cravings in people with a dependence on opioids such as heroin, Vicodin, or Oxycontin. VIVITROL is already approved for treating alcohol dependence.

It’s Alkermes’s formulation that’s new. Naltrexone as a chemical entity has been around for some time. DuPont originally marketed it as Trexan in 1984 but that form is now off-patent, as C&EN’s Ann Thayer wrote back in 2006. I also promised that there was an obesity connection here, and indeed there is. Naltrexone is one of the two components in Orexigen’s experimental obesity medication, Contrave, as I explained last year. Orexigen has developed its own proprietary sustained-release formulation of naltrexone and the experimental drug’s other active ingredient-bupropion, an antidepressant and smoking-cessation aid that boosts dopamine signaling.

Ortho-McNeil Pharmaceutical, a subsidiary of Johnson & Johnson, has agreed to pay $81 million (that’s $6.1 million in criminal fines and $75.37 million from civil suits) for promoting its epilepsy medication Topamax for several uses not approved by FDA. This story has been in the news for nearly a month now (see Pharmalot’s entry about it here) but the company pled guilty to the illegal marketing just last Friday, placing this item back at the top of my Google News list.

One of the off-label indications J&J was promoting turns out to be obesity, according to the whistleblower who brought the case. Read the legal documents here [pdf format]. Thanks to Jim Edwards at BNET for posting these.

Topiramate (the active ingredient in Topamax) is one of the two active ingredients in Vivus’s experimental obesity drug Qnexa. But Vivus’s formulation uses topiramate at a much lower dose than would be taken as a standalone drug.

Author: Carmen Drahl

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3 Comments

  1. Actually Vivus’ formulation uses a topiramate dose that is almost the same as a common maintenance dose of topiramate for migraines and seizures.

  2. Thanks for this samsonite- I’ve posted a few links about Qnexa and topiramante dosing for any who are interested (all doses are for adults).

    According to Mayo Clinic’s drug information, the migraine dosing for topiramate starts out at 25 mg- once a day for the first week, gradually working up to whatever is needed- not to exceed 100 mg/day.

    The seizure dosing is higher- starts at 50 mg once a day, and can work up to as high as 400 mg/day.

    Source: http://www.mayoclinic.com/health/drug-information/DR601527/DSECTION=proper-use

    Qnexa has been tested at a few dose levels, according to this press release describing some of the compounds’ Phase III trial results.
    http://ir.vivus.com/releasedetail.cfm?ReleaseID=407933

    The Phase 3 program evaluated three doses of Qnexa (numbers reflect milligrams of phentermine and controlled release topiramate, respectively):
    — Qnexa 15/92 (full dose)
    — Qnexa 7.5/46 (mid dose)
    — Qnexa 3.75/23 (low dose)

    So it looks like (assuming these Qnexa doses are per day) the full dose of Qnexa (which led to the highest mean weight loss in the clinical trial) is very close to the maximum recommended maintenance migraine dose of topiramate alone.

    I checked on phentermine dosing too. From the free prescription drug database Epocrates (free registration required:)
    obesity, short-term tx[18.75-37.5 mg PO qam] Max: 37.5 mg/day; Info: give before breakfast or 1-2h after; may divide dose bid, tabs may be split; do not cut/crush/chew caps; use lowest effective dose; D/C when tolerance occurs

    PO means oral administration- qam means before noon.

    Vivus’s website says that Qnexa is “an investigational, once a day, proprietary, oral, controlled-release formulation of low dose phentermine and topiramate”.
    http://www.vivus.com/pipeline/qnexa-obesity

  3. Appears Contrave hit a bump on the road to FDA approval where concern is raised about the cardiovascular safety profile of naltrexone/bupropion, ie Contrave. Do you know how more about this?