The study was a double-blind placebo-controlled study conducted in 11 countries including North America, Europe and Japan in patients with relapsing-remitting multiple sclerosis. A total of 407 patients between the ages of 18 and 55 with relapsing-remitting MS were randomized to receive placebo or one of 3 active doses of ONO-4641 once daily for 26 weeks. Patients were included in the study if they had two or more relapses in the two years prior to the study, one or more relapses within the year prior to the study or one or more new MS-related brain lesions, also known as Gd-enhancing lesions, detected on MRI within three months prior to the study. For the primary endpoint of the study, MRIs were performed every four weeks from 10 to 26 weeks, 5 times.
Results: At the end of the study, patients taking 0.05, 0.10, or 0.15 mg of ONO-4641 had 82 percent, 92 percent and 77 percent fewer Gd-enhancing brain lesions (all p<0.0001), respectively, compared to placebo. Adverse events appeared to be generally dose related. Of note was a slower heartbeat and atrioventricular blocks associated with the initiation of treatment, which were asymptomatic, transient and did not require ONO-4641 discontinuation. Other notable adverse events included liver enzyme elevations. In addition, Grade 4 ymphopenia, which is an abnormally low level of lymphocytes in the blood, occurred in 4 percent of patients receiving the 0.15 mg dose of ONO-4641 and in 1 percent of those receiving the 0.10 mg dose.
Although we need to wait until the results are published, it is not surprising that ONO-4641 can inhibit lesions in MS. However it remains to be seen how this will equate to a reduction in relapse rate, which is about 50% for Gilenya, which ONO-4641 mimics.
ONO pharmaceuticals is one of the biggest pharmaceutical companies in Japan but have licensed their drug to Merck, which is a well known MS pharmaceutical company. ONO-4641 is a sphingosine-1-phosphate (S1P) receptor agonist which keeps lymphocytes in lymph nodes and thereby inhibits the infiltration of lymphocytes into lesions. The compound is therefore expected to be a drug for the treatment of auto-immune diseases such as multiple sclerosis just as occurs with Gilenya, which is a Novartis drug that was also originated in Japan. It would be expected that phase III trials should work also but if the heart issues that have been recently occurred following use of Gilenya prove to drug-related, then this drug will have the same side effect potential, which could be the Achilles Heel of this class of molecule.
So whilst this could prove competition for Gilenya, I am sure the lawyers are sharpening their pencils ready for legal battles ahead as more and more Gilenya Me-Toos appear. However it shows that the Pharmaceutical Companies hunt targets in packs and once someone shows the value of targets, others are all over the same thing.