Estimated to be worth $3.4 billion in 2005, the migraine market is entering a state of maturity driven by the dominance of the triptan class of drugs. The ongoing approval delays with GlaxoSmithKline and Pozen's Trexima, coupled with triptan genericization, will result in the migraine market value decreasing by 20% from 2008 to $3.2 billion in 2015.
Migraine is a form of chronic neurovascular headache, in which neural events result in the dilation of blood vessels, which in turn, results in pain and further nerve activation. The pain most often occurs on one side of the head, and is usually accompanied by various combinations of symptoms, including nausea, or vomiting, and/or photophobia (sensitivity to light), phonophobia (sensitivity to sound) and osmophobia (sensitivity to smells/odours). The ideal migraine medication not only needs to be a potent pain reliever, but must also offer a rapid onset of action, sufficient duration of effects, cause minimal side effects and be easy and convenient to deliver.

FDA stalls on Trexima approval

The fate of Trexima (sumatriptan + naproxen sodium combination), GSK and Pozen's single pill combination of the market-leading sumatriptan with naproxen sodium firmly remains in the hands of the FDA. In June 2006, the FDA granted Trexima approvable, determining that Trexima is effective as an acute treatment for migraine. The agency, however, requested additional safety information on the drug, to which GSK and Pozen responded in November 2006 by submitting a complete response letter to the FDA.

In December 2006, the FDA responded to the November filing with the request for additional information, helping compare the newly submitted phase IIIb data with previously submitted phase III data in the original NDA. With Pozen and GSK responding to this latest request in early February 2007, Datamonitor assumes that the FDA is probably most concerned with the potential drug-drug interaction between naproxen and sumatriptan, and anticipate that the February 2007 response was sufficient to gain approval, resulting in a late Q2 to mid Q3-2007 launch.

Imitrex franchise extension

GSK's Imitrex (sumatriptan) franchise dominates the migraine market and posted sales of $1.1 billion in 2005, accounting for 32% of the market share. Imitrex growth has been seen to plateau over the last five years, with price increases counteracting the slight decline in volume sales. With generic manufacturers such as Teva and Dr Reddys scheduled to launch generic sumatriptan in the US in Q4-2008, GSK must rapidly and aggressively market Trexima upon approval in an attempt to convert Imitrex patients over to the new brand and protect their lucrative franchise.

However, Datamonitor forecasts Trexima sales to peak only two years after launch at $329 million in 2009. This forecast value is relatively low due to the availability of generics of both components of the tablet at a significant price reduction, and through offering a greater freedom in personalizing the dosing ratio.

Triptan genericization

The late-stage pipeline for new migraine therapies sees a number of reformulations aiming to capitalize on the maturing market. In addition to Trexima, the most promising abortive medications in development are being investigated under NovaDel, Zogenix and ProEthic. Both NovaDel and Zogenix are developing reformulations of sumatriptan, utilizing their proprietary delivery systems, whilst ProEthic is developing diclofenac potassium (PRO-513), a reformulation of diclofenac.

However, the market success of these pipeline drugs is going to be severely restricted by generic triptan availability. In the US, these are expected to be priced at a 75% discount, and therefore will be able to attract a significant patient population.

While innovation in treating migraine is lacking in a late-stage pipeline stocked largely with reformulations, there are novel formulations in the early stage pipeline which may eventually signal the end of the triptan era. Glutamatergic receptor inhibitors, nitric oxide synthase inhibitors and calcitonin gene-related peptide antagonists have all shown promising results in early stage trials. But with the most advanced of these classes only in phase II trials, the triptans or their generic versions will continue to hold their vice-like grip on the market for some time yet.

Related Research

• GlaxoSmithKline Inc: LSA Company report

• Pozen Inc: LSA Company report

• Pipeline Insight: Migraine - Innovation essential as weak late-stage pipeline fails to hold off the impact of triptan patent expiries

• Commercial Insight: Migraine - A Painful Future for the Triptans?