Alemtuzumab – Potential in Multiple Sclerosis

Alemtuzumab (Campath/MabCampath) is an anti-CD52 monoclonal antibody (MAb) for which Bayer HealthCare holds exclusive global marketing rights. It was licensed in 2001 for the treatment of chronic lymphocytic leukaemia.

However, it is seen as having potential in other therapeutic areas, including multiple sclerosis (MS). In collaboration with Genzyme Corporation, Bayer is exploring its use in the treatment of MS, for which Phase III clinical trials started in 2007.

In September 2009, Genzyme announced that the four-year follow up data of its Phase II trials for MS showed significant reductions in relapse rate by 72%. The data showed sustained accumulation of disability by 73% three years after the patients received their last dose of the investigational compound alemtuzumab.

Genzyme also announced that enrolment for CARE MS-II trials was completed. Enrolment for CARE MS-I was completed earlier in the year. Results of the CARE MS-I trial are expected in spring 2011. Results of the CARE MS-II trial are expected in autumn 2012. The company is planning for regulatory filings in 2011 and approval by 2012.

Demyelinating diseases

MS is an inflammatory autoimmune-mediated disease of the nervous system characterised by recurrent relapses followed by periods of remission. After trauma, it is the second most common neurological disability to affect young and middle-aged adults. It affects twice as many women as men, with the relapsing forms of MS the most common.

Patients with MS display a range of symptoms that arise from demyelination (loss of myelin sheath) in the central nervous system (CNS), which includes the brain, spinal cord and optic nerves.

While symptoms vary between patients, they commonly include blurred vision, slurred speech, numbness or tingling in the limbs and problems with balance and coordination, due to the loss of control over vital functions such as seeing, walking and talking.

Alemtuzumab is a highly specific MAb that binds to the CD52 cell surface antigen present on B and T cells as well as natural killer cells and monocytes where it induces antibody-dependent cytotoxicity and cell death (apoptosis). By targeting cells implicated in autoimmune–mediated destruction of the nervous system, alemtuzumab suppresses the immune attack and may help address the root cause of MS.

Alemtuzumab advances to Phase III in MS

A growing body of data suggest that treatment with alemtuzumab may be effective in patients with relapsing-remitting MS and potentially more effective than existing treatments.

In the CAMMS223 Phase II trial, involving 334 treatment-naïve MS patients, the proportion of clinically disease-free patients was significantly higher in alemtuzumab-treated patients than in the interferon beta-1a (Rebif) group over three years: 86 vs 63% at year 1, 81 vs 48% at year 2, and 71 vs 39% at year 3; p-values <0.0001. 'Clinically disease-free' was defined as the absence of both relapses and sustained accumulation of disability during the assessment period.

With Bayer support, Genzyme initiated two Phase III trials. CARE-MS I (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis), a randomised, rater-blinded study, will compare alemtuzumab to interferon beta-1a (Rebif) in treatment naive patients with relapsing-remitting MS. In contrast, the CARE-MS II trial will study patients who have continued to relapse while on approved MS therapies.

Bayer MS portfolio

The advent of the first generation of disease-modifying drugs, which include interferon beta-1a and 1b as well as glatiramer acetate, represented an important advance in the treatment of MS when introduced into clinical practice. Approved for the treatment of relapsing forms of MS, they reduce the frequency and severity of exacerbations as well as the number of lesions seen on MRI.

Bayer Schering Pharma (the pharmaceutical arm of Bayer HealthCare) is an established player in this market with Betaferon (interferon beta-Ib), the first disease-modifying drug to be introduced for MS. With alemtuzumab, the company has the potential to expand its treatment options for MS patients. At present, alemtuzumab is only an investigational agent for MS and its use is confined to the formal clinical trial setting where patient safety can be closely monitored.

Marketing commentary

Multiple sclerosis is a chronic and disabling disease, with healthcare costs disproportionate to the numbers affected. In the US alone, costs are estimated to exceed $10bn a year. The introduction of interferon beta-1a revolutionised treatment for many patients with MS and fuelled the growth of the worldwide market for MS therapies.

Drug safety has been a concern with some newer MS treatments and is something on which regulatory authorities are increasingly focusing attention. As a licensed medication, alemtuzumab has a well-documented side-effect profile, of which immune thrombocytopaenic purpura is a recognised serious side effect.