After Merck KGaA rejection, Apitope advances MS drug on strength of phase 2a safety, lesion reduction data

Apitope has posted phase 2a data on the multiple sclerosis drug Merck KGaA walked away from last year. The single-arm study linked immunotolerizing peptide-based candidate ATX-MS-1467 to a drop in total and new neurological lesions, giving Apitope the confidence to forge ahead with plans to run a phase 2b trial.

Merck initiated the phase 2a trial after taking control of the program following early-stage work by Apitope, only to decide last year to back out of 2009 agreement that gave it global rights to the asset. That move left Apitope without a shot at collecting what remained of the €154 million ($162 million) Merck committed to when it bought into the program, but with an unpartnered asset on the cusp of delivering phase 2a data.

Apitope has now presented a first look at the phase 2a results. The trial screened 93 patients with relapsing multiple sclerosis, a spokesperson for Apitope said. Of these patients, 19 were eligible to take part in the study and went through four weeks of dose titration followed by 16 weeks of fortnightly 800μg injections of ATX-MS-1467. Investigators performed MRI scans after 12, 16 and 20 weeks, and compared the average number of contrast-enhanced lesions to three scans taken in the weeks before the study started.

The comparison showed a statistically-significant reduction in new and total lesions. Apitope also reported a significant drop in the volume of the lesions. Lesions form on the brain and spinal cords of multiple sclerosis patients when the myelin that surrounds nerve cells is damaged after being attacked by the patient’s own immune system.

Apitope thinks ATX-MS-1467 can dampen this autoimmune activity by manipulating interleukin 10 secreting regulatory T cells. The goal is to stop T cells from driving a response through B cells and, in doing so, hold back the specific part of the immune system that malfunctions in patients with multiple sclerosis.

Fiddling with the immune system opens the door to safety issues, but ATX-MS-1467 has performed solidly on this front in the limited number of patients treated so far. Apitope reported the phase 2a was free from treatment-related serious adverse events, and that overall the adverse event profile was mild.

People involved with the R&D program are encouraged by the early data.

“It is pleasing to see these promising confirmatory phase 2a results where ATX-MS-1467 has shown both an encouraging efficacy and an excellent safety and tolerability profile. While these patients were only treated for 20 weeks, results in a phase 2b study with a longer treatment period will be interesting,” Jeremy Chataway, M.D., the neurologist who was chief investigator on the earlier phase 1b, said in a statement.

Apitope is preparing the placebo-controlled phase 2b now.