Datamonitor recently attended the 63rd American Academy of Neurology Annual Meeting in Honolulu, Hawaii, held over April 9-16, 2011. For another year running, developments in multiple sclerosis (MS) treatment research dominated proceedings. Below are the highlights of the conference's coverage of new multiple sclerosis drugs.
Novartis: long-term Gilenya concerns eased through additional safety analyses and extension trial data
Although Gilenya's data have been presented heavily at previous American Academy of Neurology (AAN) and international meetings, this was the first major US conference for many neurologists to see long-term data following the drug's US FDA approval. Novartis presented a pooled analysis of the cardiovascular assessments in the pivotal TRANSFORMS and FREEDOM trials stressing that the reductions in heart rate exhibited upon initial use should subside soon after first administration, while increases in blood pressure can be controlled with standard antihypertensive therapy.
To further allay concerns over Gilenya's long-term safety, Novartis presented results from a long-term five-year follow-up of Gilenya's Phase II trial. Data highlighted consistently strong efficacy for Gilenya over the 60-month extension period and while skin malignancies were reported in the first three years of therapy, no further cases were reported with chronic treatment.
Gilenya's oral dosing and strong clinical efficacy has positively raised the bar for prospective market entrants. Datamonitor believes that Gilenya will find a more prominent role in the treatment algorithm as prescribers gain more experience using the drug and learn more about the clinical data. Gilenya is forecast to capture a large share from current injectable therapies to become the leading MS therapy, as MS experts continue to treat the early-stage disease more aggressively to delay the onset of progression.
Teva: modest Phase III laquinimod data show lower efficacy than interferon betas and Copaxone
Teva presented full efficacy of the Phase III trial (ALLEGRO) for laquinimod (Teva/Active Biotech) for relapse-remitting MS. Teva reported a disappointing 23% reduction in the annualized relapse rate (ARR) for patients taking laquinimod compared to placebo; it is less than current interferons and a great deal less than Gilenya (ARR=54%), however, laquinimod is relatively benign compared to Gilenya, which has several reported safety issues.
Datamonitor believes that Teva will target the large number of early-stage patients in whom Gilenya's greater efficacy is not required, and also patients who discontinue treatment due to injection site reactions. It seems likely that laquinimod will become the second oral therapy to enter the market and will help partially defend Teva's MS franchise. However, with neurologists treating MS more aggressively earlier to prevent progression, laquinimod is unlikely to particularly trouble Gilenya.
Biogen Idec: extensive MS pipeline shows company's resolve to maintain its market-leading position
Biogen reported early strong efficacy results of ocrelizumab's efficacy and safety results of a Phase II trial. Although the 48-week data did not show any major adverse effects, there was one reported death due to systemic inflammatory response syndrome after 24 weeks. The death mars ocrelizumab's exciting early efficacy data. Although Roche and Biogen stress that the inflammatory condition in this case was not sparked by an infection, Datamonitor believes that ocrelizumab's blockbuster status has dimmed because of the death, as its use will be restricted to only severe relapsing MS patients. However, if efficacy in primary progressive MS (PPMS) patients can be shown, then ocrelizumab would become an important option in the treatment paradigm.
Biogen presented a poster identifying the risk of contracting the potentially deadly brain infection, PML caused by the JC virus (JCV). Given PML is the main barrier to prescribing Tysabri (natalizumab), Biogen has designed a test using the anti-JCV antibody as a factor to ascertain risk of PML.
The potential identification of the virus will identify MS patients who are at risk of developing PML and the test would be adopted quickly by neurologists. Although Biogen would lose some JCV-positive patients, the drug would be used more widely in JCV-negative patients. Moreover, if patients are screened for the virus, physicians could potentially start using Tysabri earlier in the treatment algorithm as a more aggressive treatment.
Merck Serono: highlighting Movectro's strong data despite recent regulatory rejections
Merck Serono showed its ongoing commitment to MS following recent US and European rejections of its oral therapy, Movectro (oral cladribine). In addition to presenting positive Rebif post-approval analyses, Merck presented Movectro posters based on the Phase III CLARITY trials. These showed that Movectro was highly efficacious as well as being an effective therapy for patients who had previously failed treatment with injectable disease-modifying drugs. With the US and European regulators citing concerns over safety, Merck tried to allay delegates' fears over its use with a poster presenting Movectro's favorable tolerability profile and high compliance in its Phase III CLARITY study.
Incidences of cancer will be observed closely in this late-stage extension. However, if no cases are observed, Datamonitor believes that Movectro will be approved and will offer another potent therapy for relapse-remitting patients and provide competition for Gilenya.
Sanofi-Aventis and Genzyme: Lemtrada acquisition broadens promising MS portfolio
Updated data from teriflunomide's Phase III TEMSO trial were presented, Sanofi-Aventis showed that doses of teriflunomide had ARRs of 31% and a relatively clean side-effect profile. Both the ARR and delay of disease progression results indicate teriflunomide is on par with the interferon betas and Copaxone, but modestly inferior to Novartis's Gilenya.
Datamonitor recommends that Sanofi-Aventis's strategy should be to position teriflunomide as a combination therapy, which represents an attractive area if priced correctly. Sanofi-Aventis can draw on the marketing experience that it has in MS and launch teriflunomide as an adjunctive for Copaxone.
Neurologists are anxiously awaiting new results from Sanofi's other MS drug, Lemtrada (alemtuzumab), which was added to the company's portfolio after its acquisition of Genzyme. The only new lemtrada data presented were further analyses of five-year follow-up data from the Phase III CAMS223 trial, showing 87% of alemtuzumab-treated patients were free of sustained accumulation of disability and 65% did not have clinical disease activity. With most patients last treated with alemtuzumab at one year, these results demonstrate outstanding and durable efficacy, halting clinical disease activity in a significant proportion of relapse-remitting MS patients through five years.
Due to its unprecedented efficacy, Lemtrada is likely to come with a high price point, and a vigilant risk management program due to the high cases of infections. Despite this, Datamonitor believes that Lemtrada will become the most powerful therapy in the treatment algorithm. However, with its safety concerns, it is likely to be used in later-line patients that have already failed at least one treatment.