Opicinumab, an investigative treatment aiming to promote remyelination in relapsing multiple sclerosis (MS) patients, will be tested in a new clinical trial — having failed at an earlier effort, but having shown promise enough in particular patients to be worth a closer look.
In fact, the new AFFINITY study “is only possible because we learned a lot from the SYNERGY study,” Sarah Sheikh, medical director for Clinical Development at Biogen, said in an interview with Multiple Sclerosis News Today.
Sheikh spoke about opicinumab, an anti-LINGO antibody being developed by Biogen to promote re-myelination in the central nervous system of people with MS, on the first day of the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris that runs through Oct. 28.
Opicinumab failed to reach its primary goal in the Phase 2 SYNERGY trial (NCT01864148) earlier this year, but data indicated that a specific patient population did respond to the treatment, showing less disability.
For this reason, Biogen launched AFFINITY, a Phase 2b trial (NCT03222973) evaluating opicinumab as an add-on therapy at five U.S. test sites. It expects to enroll 240 relapsing MS patients on a stable dose of various disease-modifying therapies, which they will continue to use during the 72-week study.
Its primary endpoint is overall response score (ORS) — a four-component measure that takes into account changes in disability over time — in patients given the add-on therapy and those given placebo.
The fixed dose of opicinumab that will be used in AFFINITY — 750 mg — came from the results seen in the SYNERGY study concerning an optimal dose, Sheikh said. Opicinumab will be delivered intravenously in a once monthly infusion.
“In addition to the dose … the SYNERGY study has allowed us to identify a patient population that might particularly benefit from opicinumab” she added, referring to the subgroup of patients who responded to treatment in the initial study.
Sheikh emphasized the discovery of three factors predictive of a response to opicinumab: “disease duration less or equal to 20 years, and two MRI [magnetic resonance imaging] characteristics in pre-existing T2 lesions,” she said.
The MRI characteristics found are a lower baseline magnetisation transfer ratio (MTR) in lesions — a relatively new MRI measure, which may be consistent with lower myelin content — and a lower baseline diffusion tensor imaging-radial diffusivity (DTI-RD) values in the lesions that may be consistent with higher structural integrity, Sheikh said.
Biogen’s main goal “is to improve disability, not to slow the disability progression … but to improve the pre-existing disability that patients have today,” she said. “And nobody has ever achieved repair of the human central nervous system. So this is a very exciting time, it’s a time of great learning and opportunity.”
While the SYNERGY study was conducted in MS patients receiving Avonex (interferon beta-1a), AFFINITY will also include patients using other disease-modifying therapies. These include three big therapeutic groups: interferon-based treatments like Avonex, Plegridy, or Rebif; an oral therapy like Tecfidera (dimethyl fumarate); and an infusion therapy like Tysabri (natalizumab).
Biogen has a long-standing commitment to the MS community, and remains dedicated to advancing MS treatments and to better understanding the therapeutic potential of repairing damage caused by the disease, Sheikh said.
“The AFFINITY study,” she said, “is a particularly good example of our commitment to learn and further our understanding of science, but really [also] to try to improve the lives of patients.”
AFFINITY is now recruiting eligible patients; more information is available on its clinical trials.gov webpage.
The complete audio interview with Sheikh can be heard below: