Tecfidera Has No Impact on PPMS Progression After 2 Years: Trial Data
Patients in Phase 2 trial remain stable with or without treatment
Continuous treatment with Tecfidera (dimethyl fumarate) for more than two years did not slow clinical and radiological measures of disease progression in people with primary progressive multiple sclerosis (PPMS) compared with patients who started treatment after one year.
In fact, most PPMS patients remained stable with or without dimethyl fumarate treatment.
These are the findings from the FUMAPMS Phase 2 trial (NCT02959658) — the first randomized trial that assessed Tecfidera versus a placebo in PPMS — and its open-label extension part.
“We found no obvious effects of treatment with dimethyl fumarate in the open-label, extended phase of the randomized, controlled trial, where patients were offered open-label treatment with dimethyl fumarate for 48 weeks after the initial 48 weeks of treatment with either dimethyl fumarate or placebo,” the researchers wrote.
The study, “Dimethyl fumarate treatment of primary progressive multiple sclerosis: results of an open-label extension study,” was published in the journal Multiple Sclerosis and Related Disorders.
Trial finds no benefits in PPMS
Tecfidera is a multiple sclerosis (MS) therapy developed by Biogen, with several generic formulations also available. It is approved by the U.S. Food and Drug Administration for the treatment of relapsing forms of MS, but not for PPMS.
Now, a team of researchers in Denmark sought to assess if Tecfidera could be a potential therapy for the progressive form of MS. To that end, the researchers conducted a Phase 2 trial investigating twice-daily treatment with Tecfidera or a placebo for nearly one year (48 weeks).
The study was funded by Biogen, with grants from the Danish Multiple Sclerosis Society. Biogen also provided the study drug and placebo at no cost.
After completing the study’s first part, patients could join an open-label extension portion, in which all would receive the active medication for another 48 weeks.
The main goal of the randomized part was to assess changes in neurofilament light chain (NfL), a biomarker of nerve cell damage, in the cerebrospinal fluid, which is the liquid surrounding the brain and spinal cord. However, the trial failed to met that goal, as well several other secondary measures of efficacy.
From the 54 participants enrolled in the first part, 42 decided to join the open-label extension and 33 completed all assessments at 96 weeks.
The findings were generally similar to those in the randomized part, with patients in the continuous Tecfidera group and delayed treatment group both showing stable clinical and MRI measures of disease severity. Likewise, serum NfL concentrations were not different between groups after 48 weeks and remained stable at 96 weeks, or nearly two years.
“We found no evidence of differences in clinical and MRI measures between patients initially treated with dimethyl fumarate and patients initially treated with placebo from baseline to week 48 and from week 48–96, where all patients were treated with dimethyl fumarate,” the researchers wrote.
“Our results show that PPMS patients, on average, are clinically and MRI stable over 2 years, with or without dimethyl fumarate treatment,” they added.
Some surprising results
In total, 42% of patients in the extension part experienced worsening in at least one physical measure of MS. These assessments included the expanded disability status scale, which measures disease severity, the timed 25-foot walk, a test of walking function, and the 9-hole peg test, which measures dexterity.
The findings were in line with the expected worsening of the physical condition of patients with PPMS over time.
But surprising to the team were results showing that a similar proportion of participants (46%) experienced improvements in one or more of those scales.
These physical improvements “are likely explained by optimization of supportive measures by the trial personnel, e.g., referral for physical therapy and perhaps some degree of learning effects,” the team wrote. But because reports of improvements in PPMS over time are scarce, “our finding of a substantial degree of improvement is very interesting in itself,” the team added.
There also were 16% of patients whose cognition improved over the two years, compared with 6% with worsening cognition.
Our results show that PPMS patients, on average, are clinically and MRI stable over 2 years, with or without [Tecfidera] treatment
Adverse events in the extension part of the trial were similar to those reported in the first part, except for fewer reports of flu-like symptoms and flushing. Five serious adverse events occurred, but none were deemed to be caused by Tecfidera.
Overall, Tecfidera treatment “showed no effects on neither clinical nor MRI outcomes or changes in serum concentrations of NFL. An expected number of patients showed evidence of progression on standard clinical scales; however, this was matched by an equal number of patients improving,” the researchers concluded, adding that the reasons for such an improvement “must be addressed in future studies.”
The small size of the extension part of the trial, with only 33 patients completing all 96 weeks, was a limitation that impeded the researchers from analyzing some of the MRI findings in more detail, among other issues, the team noted.