The three-year march to approval for Treximet , the migraine drug from GlaxoSmithKline plc and Pozen, might end with little reward, as the combo therapy faces reimbursement trouble and a challenge from generic versions of GSK's Imitrex .

Treximet's potential woes recall those of Lexington, Mass.-based Nitromed with BiDil , the isosorbide/hydralazine combo for heart failure in African-Americans.

Both drugs in the pill were available as generics when BiDil won approval in June 2005, and BiDil failed to catch on with doctors. At the start of the year, Nitromed cut jobs from 90 to 20 and quit marketing the drug (¹ Also see "NitroMed Looks To 2010 NDA For BiDil XR" - Pink Sheet, 16 January, 2008.).

Nitromed has bet its future on an extended-release BiDil version that could provide an edge.

Treximet, which pairs 85 mg of sumatriptan - the active ingredient in Imitrex - with 500 mg of long-available naproxen, was cleared by FDA April 15 (² Also see "GSK/Pozen Win Long-awaited Approval For Combo Migraine Drug" - Pink Sheet, 16 April, 2008.).

Well ahead of Treximet's approval, analysts rumbled about the possibility that doctors would prescribe generic versions in an identical recipe, thus cutting into sales.

Generic Imitrex is expected to reach the market late this year, and consumers know naproxen best as Bayer's over-the-counter pain drug Aleve , a non-steroidal anti-inflammatory compound.

In an April 16 research note, Lazard Capital Markets cited its survey of neurologists and general practitioners that led to a forecast of $320 million in peak Treximet sales, only 15 percent of the market held by GSK-pioneered triptans, which make up the most widely prescribed oral migraine therapy.

Cowen analyst Steve Scala, in an April 21 report, said a pharmacy benefit manager expert predicted that London-based GSK will convert less than 10 percent of Imitrex scripts during the next year.

Scala predicted Treximet sales of $350 million in 2012, though the expert consulted by Cowen allowed that Treximet "will do better with more severe patients."

As Treximet's fate works itself out, Merck's MK-0974, an oral calcitonin-gene related peptide antagonist due to report Phase III data in June, could turn into a blockbuster, analysts say.

Cowen's expert expects results with the Merck drug to match favorable Phase II data compared to Merck's own Maxalt (rizaptriptan), beset - like others in the class - by cardiovascular risks.

Whitehouse Station, N.J.-based Merck aims to file the NDA for MK-0974 next year, though FDA might want more data.

Earlier this month, Endo Pharmaceuticals, of Chadds Ford, Pa., decided not to pursue FDA approval of a new, menstrual-headache indication for the migraine treatment Frova (frovatriptan), after a not approvable letter last year that highlighted the potential for cardiovascular trouble (³ Also see "FDA “Not Approvable” Letter Questions Benefit Of Endo’s Frova In Menstrual Migraine" - Pink Sheet, 1 October, 2007.).

Another migraine candidate coming down the Phase III pike is tonabersat, the gap junction blocker from Cambridge, U.K.-based Minster Pharmaceuticals.

Allergan, of Irvine, Calif., is trying its wrinkle remedy Botox (botulinum toxin) in migraine, too, though the drug failed in Phase II, and cost could limit its use to patients in whom neither triptans nor the Merck drug works, Scala wrote.

The migraine market is ripe. American Medical Association estimates that 26 million people in the U.S. suffer from the headaches, and many patients get opiates because of the risks with triptans, even though opiates do not work as well, Scala pointed out.

- Randall Osborne (r.osborne@elsevier.com)

GSK’s Treximet Could Face Market Headaches

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