Firm says Gilenya is first oral treatment for relapsing MS to be sanctioned in U.S.

FDA has approved Novartis’ oral multiple sclerosis (MS) treatment ,Gilenya™ 0.5 mg daily, as first-line treatment for relapsing forms of the disease. Novartis separately reported on Phase III trial data demonstrating that Cushing disease patients treated using pasireotide (SOM230) demonstrated significant reductions in urinary-free cortisol (UFC) levels and improvements in clinical symptoms including blood pressure, total cholesterol, and weight loss. The firm says it plans to file for approval of SOM230 during 2010.

Gilenya has been approved with a Risk Evaluation and Mitigation Strategy (REMS) and is the first oral therapy for relapsing MS to be sanctioned in the U.S., the firm notes. Regulatory review in the EU is in progress. FDA clearance of Gilenya was based on trial data demonstrating that in comparison with Biogen Idec’s Avonex® therapy, the new Novartis’ drug reduced relapses in MS patients by 52% at one year. Gilenya also led to reduced disease activity as measured by the number of new or newly enlarged T2 lesions compared with interferon beta 1a IM treatment, and resulted in statistically significant reductions in brain lesion activity.

Two-year data from a placebo-controlled trial in addition showed that treatment with Gilenya led to a 54% reduction in relapse rate and a 30% reduction in risk of disability progression. The drug is a sphingosine 1-phosphate receptor (S1PR) modulator, which Novartis says is thought to work by inducing immune cells to remain in lymph nodes and so prevent them from migrating into the brain and spinal cord where they cause damage.

Biogen Idec, which markets the MS drugs Avonex and Tysabri®, admits that an oral therapy for relapsing MS has been awaited for some time. “The approval of Gilenya has made this a reality,” the firm stated on the announcement of Gilenya’s approval. Phase III data from Biogen Idec’s own oral MS therapy, BG-12, is expected during 2011. The company says prior clinical evidence suggests that BG-12 may have the potential to both reduce inflammation and promote neuroprotection.

Meanwhile, the pivotal trial evaluating Novartis’ SOM230 in Cushing disease patients represents the first ever to show efficacy at the Phase III stage, the company claims. There are currently no approved therapies for the disorder. Cushing disease is caused by a benign pituitary gland tumor that secretes adrenocorticotropic hormone (ACTH) and triggers the adrenal glands to produce excess cortisol.

The registrational trial with SOM230 involved 162 patients with persistent or recurrent Cushing disease, and those with newly diagnosed disease that could not be addressed surgically. Participants with primarily moderate to severe hypercortisolism were randomized to receive either 600 μg or 900 μg doses of SOM 230 twice daily, administered subcutaneously. After six months the proportion of patients who achieved normalization of UFC was 26.3% for the high dose group, and 14.6% for the low dose group. Median reductions in UFC after 12 months were 67.6% and 62.4%, respectively.

SOM230 is a pituitary-directed therapy designed to target multiple subtypes of the somatostatin receptor, including sst5, which is frequently expressed by pituitary tumors associated with Cushing disease. Novartis says the ability to bind sst5 sets SOM230 apart from other somatostatin analogs, which preferentially bind to sst2 and are not effective against Cushing disease. The firm is developing SOM230 both as a twice-daily subcutaneous injection, and also as a long-acting release once-monthly intramuscular injection for the treatment of disorders including Cushing disease, carcinoid syndrome, and acromegaly. SOM230 has been granted orphan drug designation for Cushing disease in the U.S. and Europe.

“Up to half of patients with Cushing disease cannot be cured with currently available options, which include surgery or radiotherapy of the tumor, leaving a critical need for medical treatments,” states Annamaria Colao, M.D., one of the Phase III SOM230 trial investigators and professor of endocrinology and chief of the neuroendocrine unit at the department of molecular and clinical endocrinology and oncology, Frederico II University of Naples. “The study findings show that SOM230 has the potential to directly target the underlying pituitary tumor and suppress cortisol production, thereby helping patients achieve biochemical control of their Cushing disease and the associated debilitating symptoms.

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