- Swiss pharma Novartis AG aims to bring to market the first disease-modifying treatment for a type of later-onset multiple sclerosis, planning to soon submit its experimental drug candidate siponimod for U.S. approval.
- Results from a Phase 3 study, published in full for the first time Thursday in the journal The Lancet, show siponimod reduces the risk of disability progression in patients with secondary progressive MS by roughly a fifth versus placebo.
- Over time, MS patients can advance from the more common relapsing/remitting form of the disease to SPMS, at which time disability and neurological function progressively worsens. One in four people with RRMS eventually develop SPMS within the 10 years following an initial diagnosis, according to data cited by Novartis.
Despite a market already crowded with treatments, drugmakers remain eager to develop new medicines for MS — a chronic disorder that affects over two million people worldwide.
For Novartis, siponimod would bolster a franchise led by the pharma's aging top-seller Gilenya (fingolimod). Approved in 2010 for RRMS, Gilenya earned Novartis nearly $3.2 billion last year even in the face of stiff competition from rival drugs made by Biogen Inc., Sanofi SA and Teva Pharmaceutical Industries Ltd.
A key patent for Gilenya, however, expires next year, likely opening the door to entry of generic copies.
Novartis hopes siponimod could eventually become a blockbuster itself, offering an option to the more than 120,000 SPMS patients in the U.S. and five major EU countries.
The Swiss pharma's task may be easier, though, after the Food and Drug Administration last month turned back Celgene Corp.'s application for approval of its rival ozanimod in a surprise rejection. Both siponimod and ozanimod bind to subtypes of a receptor known as S1P.
EXPAND, as the trial testing siponimod is known, is the largest randomized study of SPMS patients conducted to date, enrolling 1,651 patients.
"This is the first and only study that managed to show efficacy of an immunomodulator in a very typical secondary progressive MS patient," said Danny Bar-Zohar, head of neuroscience development at Novartis.
Results, some of which had previously been presented at medical conferences, demonstrated siponimod cut the risk of disease progression at three months by 21% compared to placebo, and by 26% at six months. Treatment with the drug also slowed lesion growth and the rate of brain volume loss — supporting a neurological benefit.
Patients in the siponimod arm did not, however, see any improvement over placebo in either the Timed 25-Foot Walk test or MS Walking Scale — a result Novartis' Zohar chalked up to variability and high baseline levels of disability among study participants.
Side effects, while in line with drugs similar to siponimod, were reported in most patients, with 18% of patients experiencing severe adverse events.
Novartis plans to file siponimod for approval in the EU later this year after consultation with the European Medicines Agency.
One element that remains unclear is how regulators would define SPMS in siponimod's label, if it were to be approved.
"There is no clear cut definition between relapsing remitting MS and secondary progressive MS," Bar-Zohar said. "It is a continuum and we must acknowledge that."
Zohar says Novartis is confident that any label would reflect the patient characteristics of those individuals studied in EXPAND.
Analysts from Cowen & Co. wrote in a January note that while prescribers might appreciate the differences between RRMS and SPMS patients, payers might be less discerning. The investment firm forecasts annual sales of siponimod to reach $500 million by 2024.