Staff Writer

Genzyme presented more good news from a positive Phase II multiple sclerosis study that was first reported in the New England Journal of Medicine in 2008.

The study compared alemtuzumab to approved MS therapy Rebif (interferon beta-1a) in patients with relapsing-remitting MS who had not received prior therapy. The completed results, presented at the American Academy of Neurology annual meeting in Toronto, showed an estimated 71 percent of alemtuzumab-treated patients remained free of clinically active disease as much as three years after most patients received their last course of Alemtuzumab.

"Several aspects of the data are new," said Michael Panzara, group vice president and therapeutic head of MS and immune diseases at Genzyme. The four-year data presented at AAN were an extension of the three-year period covered in the 2008 journal article. Study patients continued to be followed while off treatment, and the results showed that alemtuzumab showed efficacy in preventing relapses and in reducing disease progression.

Panzara said that what is "striking" is that patients remained free of disease disability or disease progression despite not having treatment over a significant portion of time. The study showed that 91 percent of alemtuzumab-treated patients were free of sustained accumulation of disability compared to 68 percent of patients taking Rebif.

In addition, he noted that 77 percent of alemtuzumab-treated patients were relapse-free years after the last dose, compared to 49 percent of patients taking Rebif.

Many of the 71 percent in the alemtuzumab group who had neither progressed nor relapsed at the four-year mark had not received an infusion treatment for three years, while the 35 percent who met that bar in the Rebif-treated group had continued taking three injections per week of that drug, Panzara noted.

He said the study "created a higher bar" by measuring which patients neither progressed nor relapsed. A relapse was defined as an acute event such as a sudden decrease in neurological function from which patients eventually recovered. Disease disability or progression was scored on a scale of 1-10, with an increased score indicating a decrease in neurological functions, such as the ability to walk, use hands or speak. Alemtuzumab-treated patients showed a reduction in disability scores, a sign of improvement.

The investigational drug has completed enrollment in two Phase III pivotal trials, and data are expected in 2011.

The first Phase III study seeks to replicate the Phase II observation with patients who had not received prior therapy. The second Phase III trial targets patients who were previously treated with another therapy but had an incomplete response and continue to have disease activity. Those studies will help Genzyme determine which of those two populations is the better target for alemtuzumab.

Updated four-year data from the Phase II trial found that approximately 28 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event. Those events either normalized spontaneously or were managed using conventional therapies. Patient monitoring for thyroid disorders, Immune thrombocytopenic purpura and anti-GBM disease is incorporated into all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS.

The company continues to study alemtuzumab's mechanism of action and its potential risks. Genzyme presented other data looking at the effects on B- and T-cell populations and the reconstitution of those populations. In addition, the company created an animal model in which to study the drug candidate since alemtuzumab does not bind to the mouse form of the key protein in humans, CD52.

Alemtuzumab currently is sold as Campath to treat leukemia. Campath treatment of B-cell chronic lymphocytic leukemia carries a boxed warning that includes information on cytopenias, infusion reactions and infections.

Genzyme gained control of the product through a potential $2.9 billion deal with partner Bayer AG. Genzyme obtained rights to the marketed cancer drugs Campath, Fludara (fludarabine) and Leukine (sargramostim) - as well as control of the Phase III alemtuzumab program in multiple sclerosis. In fact, the alemtuzumab multiple sclerosis program accounted for the bulk of the financials associated with the deal. (See BioWorld Today, April 1, 2009.)

Shares in Genzyme (NASDAQ:GENZ) were up 23 cents, closing at $52.66.

In other news from the AAN meeting:

• Acadia Pharmaceuticals Inc., of San Diego, reported additional data from the first Phase III trial of pimavanserin in Parkinson's disease psychosis, which showed that the 40-mg treatment arm consistently demonstrated signals of efficacy across measures such as the Scale for the Assessment of Positive Symptoms, the Clinical Impression of Improvement scale, the Scales for Outcomes in Parkinson's disease nighttime sleep measure and caregiver burden scale. The company reported in September that the study had missed showing statistical significance in the primary endpoint of antipsychotic efficacy, though it hit secondary endpoints. (See BioWorld Today, Sept. 2, 2009.)

• MAP Pharmaceuticals Inc., of Mountain View, Calif., said that additional post-hoc analyses of data from the FREEDOM-301 Phase III trial of Levadex orally inhaled migraine therapy showed efficacy in two difficult-to-treat patient subpopulations, menstrual migraine and migraine with allodynia. Those subpopulations often are difficult to treat with currently available therapies, such as triptans.

• Synosia Therapeutics, of Basel, Switzerland, presented data from a Phase IIa study of its adenosine 2a (A2a) receptor antagonist (SYN-115) in Parkinson's disease. The data showed that SYN-115 significantly improved measures of motor and nonmotor function in patients with Parkinson's disease either alone or in combination with levodopa. SYN-115 is a selective inhibitor of the A2a receptor. Synosia obtained rights to SYN-115 from Roche in 2007 for development in selected indications of the central nervous system.

• UCB Pharma Inc., of Atlanta, reported evidence of Neupro (rotigotine transdermal system) improving motor as well as nonmotor symptoms of Parkinson's disease. In April 2008, UCB recalled Neupro from the U.S. market after ongoing monitoring revealed that specific batches of the drug had deviated from their approved specification. Neupro is currently not available in the U.S. UCB is working with the FDA so that Neupro can be available to patients with early stage Parkinson's disease as soon as possible.