A Genzyme spokesperson denied the similarity between the two business cases, however. "We believe the situation that we are managing with alemtuzumab is unique," he said in an e-mail exchange.
Sanofi/Genzyme made its decision on withdrawing Campath gradually, and consulted the MS and oncology communities, including patient advocacy groups, along the way, the spokesperson added.
"We are changing the way Campath is made available for its current use because we have decided to focus on bringing alemtuzumab forward for MS, where it holds the potential to address a significant unmet need," he said. "Importantly, this step will also help ensure that the product is used for MS patients only within the clinical trial setting prior to approval, given the differences in dosing and safety profile associated with its use in CLL and MS."
Because Lemtrada is a lower dosage of alemtuzumab than is Campath, it has a different safety profile. The MS space offers multiple therapeutic options, but each – including Lemtrada, if approved – poses potential safety issues.
Biogen Idec Inc. and Elan Corp. continually have battled reports of progressive multifocal leukoencephalopathy (PML) in patients treated with their drug, Tysabri (natalizumab), which claimed 12% of the MS market in 2011, garnering sales of $1.5 billion. Sales have picked up in recent months now that patients can use a diagnostic to predict their risk for PML.
Novartis AG markets a once-daily oral drug for MS, Gilenya (fingolimod), which launched in 2011, claiming a 4% share of the market and sales of $494 million. That product, however, sometimes presents cardiovascular side effects.
In a pivotal trial testing alemtuzumab in relapsed, remitting MS, Sanofi/Genzyme found that 15.9% of treatment-arm patients experienced autoimmune-related thyroid adverse events, compared with just 5% of control-arm patients who received Roche’s Rebif (interferon beta-1a). Meanwhile, 0.9% of the alemtuzumab recipients developed immune thrombocytopenia over a 2-year treatment period.
Genzyme, which has a management program in place to detect and treat both types of adverse events, says that even higher rates of autoimmune effects have been seen in MS testing with the antibody, but more than 90% of such cases are mild to moderate in severity and are treatable with standard therapies. At the 30-mg dosage used for CLL, the Campath label includes warnings for risk of cytopenia, infections, and infusion reactions.
Dosing, Efficacy Advantages Expected in MS
Dosing and efficacy both are expected to give Lemtrada a potential leg up in the MS space. Lemtrada would be dosed much less frequently than other MS drugs, although it would not offer the convenience of oral availability presented by Gilenya. An intravenous infusion drug, Lemtrada would be dosed at 12 mg for 5 consecutive days during the first year of treatment and then for 3 consecutive days the following year.
In the CARE-MS II trial, alemtuzumab reversed disability in nearly one-third of patients whose disease had relapsed while they received other therapy. Top-line data showed a 49% reduction in relapse rate, compared with patients treated with Rebif, along with a 42% reduction in worsening of disability. Longer-term data from the trial showed a reduction in disability, as measured by the Expanded Disability Status Scale, for treatment-arm patients, whereas control-arm patients saw increased disability.
In December 2010, while the Sanofi acquisition of Genzyme was being negotiated, Genzyme offered projections that Lemtrada would achieve 5% market share in its launch year, moving up to 10% and 12% in years 2 and 3 on the market, and an 18%-20% share by year 5. At that time, then–Genzyme executive Mark Enyedy acknowledged concerns "about managing the use of the oncology product in MS" and talked of a range of solutions, which included pulling Campath from commercialization.
Perhaps the most bullish on Lemtrada’s market potential is Stephen McGarry, an analyst with Société Générale Cross Asset Research. He projects Lemtrada’s reaching 472 million euros in sales by 2016 and continuing to grow, peaking at 1.134 billion euros in 2020. "Although we view the side effect profile as a negative relative to competing drugs in the MS space, and its route of administration is not oral, which is also a potential disadvantage, the dosing frequency and high level of efficacy more than balance those concerns in our view," he wrote in an Aug. 9 note.
Sanofi has another MS candidate, Aubagio (teriflunomide), pending at the FDA with a Sept. 12 action date. It plans to position Aubagio, an oral pill, as a convenient therapy for patients in early stages of MS, whereas Lemtrada would be targeted to those with more serious, later-stage disease.