Alzheimer's disease: hope remains despite setbacks
There remains an enormous unmet need in the treatment of Alzheimer's disease. For the millions of elderly people worldwide, there are just four drugs available that can only offer a modest symptomatic effect. Even so, these treatments cannot slow or modify the course of this neurodegenerative disease, which is the ultimate goal in Alzheimer's therapy. While it was announced in March 2010 that in a Phase III trial Medivation/Pfizer's Dimebon (latrepirdine) failed to meet any of its clinical endpoints, there remains hope in the pipeline for Alzheimer's sufferers and their caregivers. One such drug, Baxter's Gammagard (intravenous immune globulin; IGIV), is actively recruiting for a Phase III trial, and at the American Academy of Neurology Annual Meeting (AAN 2010) the company presented new data from the extension phase of its Phase II trial.
Gammagard is a human antibody preparation already launched for the treatment of primary immunodeficiency diseases in the US and Western Europe. The drug is currently being assessed in Phase III clinical trials in patients with mild-to-moderate Alzheimer's disease. At AAN 2010, Baxter presented clinical trial results for the first time measuring function and cognition in patients who received uninterrupted Gammagard for a period of 18 months for mild-to-moderate Alzheimer's disease. After 18 months, patients who received Gammagard continuously averaged approximately 1.36 points higher than patients who initially received placebo on the Alzheimer's disease Cooperative Study-Clinical Global Impression of Change rating (ADCS-CGIC).
While clarifying that the study involved only a very small number of patients, Baxter is clearly encouraged by these data and has stated that it plans to initiate a second, concurrent Phase III study of the drug in this patient population. However, in light of the recent setback with Dimebon and other numerous late-stage trial failures in the last 10 years, Datamonitor remains cautious about Gammagard's prospects until Q3 2011 when results of the 360-patient Phase III study are expected.
Epilepsy: long-term data for new drugs the highlight
The second half of 2008 and first half of 2009 saw a flood of generic second-generation anticonvulsants enter the US market as Lamictal (lamotrigine; GlaxoSmithKline), Keppra (levetiracetam; UCB), Depakote IR and ER (valproate semisodium; Abbott) and Topamax (topiramate; Johnson & Johnson) lost patent protection. As the market environment for new and prospective drug candidates becomes increasingly price-sensitive and competitive, both Valeant/GlaxoSmithKline and UCB presented long-term safety and efficacy data for their respective novel anti-epileptic candidates in order to support their positions in the growing treatment arsenal.
Valeant's retigabine is a first-in-class anti-epileptic drug that reduces neuronal excitability by enhancing the activity of neuronal KCNQ (Kv7) potassium channels and through its gamma aminobutyric acid type A (GABA-A) receptor agonistic properties. In August 2008, Valeant entered into an exclusive worldwide collaboration agreement for retigabine with GlaxoSmithKline, and in October 2009 the companies filed a New Drug Application (NDA) in the US and a Marketing Authorization Application (MAA) in Europe for the adjunctive treatment of partial-onset seizures in adults with refractory epilepsy.
The efficacy and safety of retigabine in patients with refractory partial-onset epilepsy was demonstrated in two pivotal Phase III trials, RESTORE 1 and RESTORE 2. At AAN 2010, Valeant provided insight into the maintenance of efficacy and the safety profile of retigabine at doses of 600mg-1,200mg/day, as demonstrated in the long-term open-label extensions of the trials. With 81% of patients transitioning from RESTORE 1 and 92% doing so from RESTORE 2, median percent reduction in 28-day total partial-seizure frequency was 57% and 53%, respectively. Furthermore, safety assessments supported what Valeant called an acceptable safety profile for an adjunctive therapy.
With both US and EU regulatory bodies currently appraising the drug, Datamonitor believes that the inconvenient dosing regimen and reasonably high level of treatment-related side effects will deter some treatment-refractory epilepsy patients and their physicians from using retigabine, despite the strong efficacy data demonstrated thus far.
UCB's Vimpat (lacosamide) was the subject of numerous studies and analyses at this year's AAN conference. Indicated as an adjunct therapy for the treatment of partial-onset seizures in adults with epilepsy, Vimpat was approved in the EU in September 2008 and shortly after in October in the US, making it one of the most recent novel entrants to the epilepsy market. Although monotherapy trial data is anticipated by mid-2011, long-term analysis from adjunct trials presented on the conference provides additional support to Vimpat's growing safety and efficacy profile.
Data presented during the meeting focused largely on providing long-term safety/tolerability and efficacy of Vimpat from Phase II-III double-blind and/or open-label extension trials. While one study reported the efficacy of Vimpat in cohorts of patients completing successively longer durations of lacosamide exposure, another indicated that lacosamide improved 50% responder rates and reduced median seizure frequencies by up to 42% and 86% for complex partial seizures and secondarily generalized seizures (the two most commonly reported seizure types), respectively. A third poster provided insight into the drug's long-term safety profile; an important consideration for a drug dosed in such a chronic fashion.
However, with questions previously raised regarding the drug's side-effect profile in comparison to first-line treatments like levetiracetam and lamotrigine, Vimpat is likely to encounter difficulty in taking significant market share from its well-tolerated competitors. Datamonitor predicts that potential future indication expansions in pediatric patients as well as primary generalized tonic-clonic seizures will hold the key for Vimpat's commercial success in epilepsy.