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| Director, Neurology Clinical Research Professor, Department of Neurology UNIVERSITY OF COLORADO Co-Director, Rocky Mountain MS Center at Anschutz Medical Director, ROCKY MOUNTAIN MS CENTER |
Patients taking alemtuzumab -- first sold under the brand name Campath for treating B-cell chronic lymphocytic leukemia -- had a mean annualized relapse rate of 0.18 during a two-year, phase III trial, compared with 0.39 for patients receiving the standard regimen of interferon. But another neurologist not involved with the study suggested that the drug's safety profile remains a major concern.
Timothy Vollmer, MD, of the University of Colorado in Denver, said the extreme duration of alemtuzumab's effects was itself a potential problem.
"[It] induces long-term if not permanent changes in immunoregulation; it also induces significant generalized immune suppression and disturbance of immunoregulatory circuits," he observed.
As a result, said Vollmer, "once you treat a patient, you can't take it back. Those patients are then at risk for infections and for development of autoimmune disease."
He added that he considered these risks more worrisome than the potential for progressive multifocal leukoencephalopathy with natalizumab (Tysabri).
Coles reported findings from the 581-patient trial, dubbed CARE-MS I, during a late-breaking news session at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.
Patients in the study had disease duration of no more than five years and EDSS disability scores of 3 or less, but had active disease on the basis of relapses during the previous two years. Patients who had received disease-modifying therapies previously were excluded.
The difference in relapse rates meant the cancer drug met one of two primary endpoints in the study, which was intended to demonstrate alemtuzumab's superiority to one of the mainstays of first-line MS therapy.
Speaking with MedPage Today before his presentation, Coles said the study investigators had expected 20% of patients in the interferon arm to show disability progression. The much lower number seen in the study made it effectively impossible for alemtuzumab to demonstrate an advantage, he said.
Infections affecting the upper respiratory and urinary tracts, as well as oral herpes, were more common with the drug relative to interferon.
Also, 18% of alemtuzumab patients developed an autoimmune thyroid event and 0.8% developed immune thrombocytopenia.
Coles said these events were expected and were successfully managed with standard therapies.
Alemtuzumab targets the CD52 molecule, carried on certain T and B cells. It therefore alters immunoregulation in ways that apparently reduce autoimmune activity in MS -- but can also induce other forms of autoimmunity.
In MS, its dosing schedule is unusual compared with those for other therapies. Patients in CARE-MS I received 12 mg/day intravenously for five days, with a second three-day course one year later (for treating leukemia, the standard dose is 30 mg three times weekly for up to 12 weeks).
Because its effects on immune regulation appear to be more or less permanent, no additional dosing is planned. Under long-term extensions of CARE-MS I and earlier trials, patients may receive another course if they show renewed disease activity.
With up to four years of follow-up, Coles told MedPage Today, no patient has received more than four courses. He said in his own clinic, with 29 patients participating in the extensions, only one has needed an additional course after completing the originally scheduled treatments.
Because the schedule does not require frequent, lifelong dosing -- interferon requires three injections per week, glatiramer acetate (Copaxone) and oral medications are given daily -- almemtuzumab may be attractive to many patients even apart from the possibility of enhanced efficacy, Coles said.
Coles said a companion phase III trial of alemtuzumab involving patients with more established, pretreated MS was still underway, with completion expected soon.
Those results would help inform patients and physicians about their treatment choices, he said.
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