Merck 2010 Annual Report Download - page 64


Within our Neurodegenerative Diseases therapeutic area, we are conducting research to discover
new therapeutic options for multiple sclerosis (MS) and Parkinson’s disease – two indications
with high unmet medical needs. In REFLEX, a two-year Phase III study involving more than 500
patients, we investigated whether patients with clinically isolated syndrome (CIS) at risk of
developing MS could benefit from treatment with the serum-free formulation of Rebif ®. Study
participants with this clinical picture have so far experienced a single MS-like episode, such
as optical or sensory disturbances, and have characteristic MRI lesions, putting them at high
risk of developing clinically definite multiple sclerosis. At this early stage, these patients have
not yet been given a clinically definite diagnosis, yet they are at risk of developing MS. The
trial, which was completed in October, met its primary endpoint by demonstrating that Rebif ®
significantly delays conversion to clinically definite MS in these patients. A three-year double-
blind extension of the REFLEX study, called REFLEXION, is currently ongoing in order to provide
long-term follow-up data.

With cladribine tablets, the Merck Serono division is developing a drug for the oral, short-course
treatment of relapsing-remitting multiple sclerosis. In 2010, we received regulatory approvals
in Russia and Australia. Our regulatory application received a negative opinion in the European
Union. It is currently under review in the United States (see page 51). The clinical develop-
ment program for cladribine tablets is designed to evaluate the potential therapeutic effects
of cladribine tablets in various stages of the disease. Following the successful completion of
the CLARITY study, a two-year extension with around 800 patients is currently underway to
provide data on the long-term safety and efficacy of cladribine tablets as a monotherapy in
relapsing-remitting MS. The two-year Phase III ORACLE-MS study is investigating cladribine
tablets as a monotherapy in patients with clinically isolated syndrome. In November, we com-
pleted the recruitment of more than 600 study participants. In the Phase II ONWARD study, we
are evaluating the safety and tolerability of adding cladribine tablets to established treatment
with interferon beta.

Together with our partner Newron, we are developing safinamide as an oral adjunctive therapy
for patients with various stages of Parkinson’s disease, which affects an estimated three million
people in industrialized countries. In 2009, we had successfully completed the first Phase III
clinical trial of safinamide administered as an add-on therapy to levodopa standard treatment
in patients with advanced Parkinson’s disease (Study 016). Motor function and the ability to
perform daily activities improved significantly in patients treated with safinamide compared
to placebo. An 18-month extension study (Study 018) was intended to provide data on the
long-term efficacy and safety of safinamide in this indication. We announced the results of
this long-term study in November 2010. The primary efficacy endpoint measuring dyskinesia
after 24 months of treatment was not met. We therefore reassessed the sales potential of
safinamide and recorded an impairment (see page 19). By contrast, the results of the analysis
of the main secondary endpoint were consistent with the effect on motor function observed in
Rebif ® significantly delayed
conversion to clinically definite
MS in patients with CIS
Safinamide study misses endpoint,
but confirms effect on motor
function and safety profile
Merck Annual Report 2010 60