Biogen has released new data on several of its therapies for multiple sclerosis (MS), including Vumerity (diroximel fumarate), Tecfidera (dimethyl fumarate), and Tysabri (natalizumab).
The data — six presentations — originally were to be presented at the 2020 annual conference of the American Academy of Neurology (AAN), which was canceled due to the COVID-19 pandemic. Instead, the data were posted online.
“The data shared at AAN represent our ongoing efforts to improve the MS treatment experience and deliver therapies that provide clinically meaningful benefits to individuals living with this chronic disease,” Bernd Kieseier, MD, said in a press release. Kieseier is executive director, head of Global MS, Worldwide Medical, Biogen.
In one presentation, “Improved Gastrointestinal Tolerability Profile with Diroximel Fumarate Compared to Dimethyl Fumarate in Relapsing MS Patients,” researchers analyzed data from the clinical trial EVOLVE-MS-2 (NCT03093324).
In EVOLVE-MS-2, participants with relapsing-remitting MS (RRMS) were assigned randomly to treatment with either Tecfidera (240 mg) or Vumerity (462 mg) for five weeks. These two oral medications are different formulations of the same active ingredient — monomethyl fumarate. The main purpose of the trial was to compare the safety and tolerability of the two therapies, especially regarding gastrointestinal side effects.
Among 502 participants who rated their gastrointestinal (GI) symptoms at least once, fewer patients receiving Vumerity, compared to Tecfidera, reported that GI symptoms interfered with daily life “quite a bit” or “extremely.”
The specific symptoms were: nausea (2.4% with Vumerity vs. 6.8% with Tecfidera), vomiting (1.2% vs. 5.6%), upper abdominal pain (1.2% vs. 6.8%), lower abdominal pain (1.2% vs. 3.2%), and diarrhea (3.6% vs. 6.4%).
Also, treatment discontinuation due to GI symptoms was significantly lower with Vumerity (0.8%) than with Tecfidera (4.8%).
“GI symptoms interfered less with daily activities for [Vumerity]-treated patients compared to [Tecfidera]. Further benefits on additional measures of treatment burden, including lower medication use for GI symptoms, were seen with [Vumerity],” the researchers wrote.
In another presentation, “Diroximel fumarate and dimethyl fumarate demonstrate early clinical and radiological efficacy in relapsing-remitting multiple sclerosis,” researchers analyzed data from the clinical trial EVOLVE-MS-1 (NCT02634307).
Participants who completed EVOLVE-MS-2 had the option to enroll in EVOLVE-MS-1, an open-label extension study in which all participants were treated with Vumerity.
Currently, 82 participants have completed 48 weeks in EVOLVE-MS-1, representing about a year of total treatment.
Data now released showed that the mean number of brain MRI lesions was 1.1 prior to treatment, and was significantly reduced to 0.2 after one year of treatment with Vumerity, with 96.3% of participants being lesion-free. Significant lesion reductions were observed as early as seven weeks after starting treatment.
Three other Biogen AAN presentations focused on Tysabri. This medication is currently approved to be given by injection once every four weeks (Q4W), but extended interval dosing (EID) — in which injections are given about every six weeks — is being evaluated as a possible way to limit side effects.
In the presentation, “Serum Neurofilament Light (sNfL) Levels in Patients with Relapsing-remitting Multiple Sclerosis (RRMS) Switching from Natalizumab Every-4-week (Q4W) Dosing to Extended Interval Dosing (EID),” researchers compared the effectiveness of the two dosing schedules by measuring the levels of the protein neurofilament light (NfL) in the blood of RRMS patients. NfL is released when neurons are damaged; as such, it can be used as a marker of neurodegeneration in MS.
This analysis included 79 people with RRMS who were given the Q4W dosing schedule and 60 people who switched to EID. Levels of NfL were not significantly different between these dosing schedules.
“Patients in real-world clinical practice who switched from natalizumab Q4W to EID showed no increase in sNfL levels, supporting previous reports that EID is not associated with increased disease activity,” the researchers wrote.
Tysabri is known to potentially increase the risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection. Using data from a Tysabri prescribing database (TOUCH), which included tens of thousands of treated patients, researchers confirmed previous data and showed that Tysabri EID was associated with a reduced PML risk compared to Q4W.
These data were presented in “Natalizumab extended interval dosing (EID) is associated with a reduced risk of progressive multifocal leukoencephalopathy (PML) than every-4-week (Q4W) dosing: Updated analysis of the TOUCH® Prescribing Program database.”
Biogen is continuing to evaluate Tysabri EID in the NOVA clinical trial (NCT03689972).
In the last Tysabri-related presentation, “Updated Incidence of Natalizumab-associated Progressive Multifocal Leukoencephalopathy (PML) and Its Relationship with Natalizumab Exposure Over Time,” researchers demonstrated that the overall incidence of PML cases has remained relatively stable since mid-2016 in Tysabri-treated patients — about 4.14 cases per 1,000 patients.
“This stabilization coincides with the publication of new PML risk estimates, suggesting that risk stratification factors are being incorporated into clinical practice and may continue to impact PML incidence in the future,” the researchers wrote.
Of note, some of these PML risk factors include the presence of anti-JC virus antibodies (JC virus is the agent causing PML), prior immunosuppressant use, and longer treatment duration.
In the sixth Biogen presentation at AAN, “Interim analysis of peginterferon beta-1a in the breast milk of lactating patients with multiple sclerosis,” researchers investigated whether Plegridy (peginterferon beta-1a, under-the-skin injection) was present in the breast milk of six women with MS who started treatment after beginning lactation.
The highest recorded Plegridy concentration in breast milk was 126.2 picogram (pg)/mL; average values were 56.9 pg/mL after five days and 27.4 pg/mL after 14 days. Of note, in a previous study using Avonex (intramuscular interferon beta-1a ), the highest observed breast milk concentration was 179 pg/mL, with an estimated relative infant dose of 0.006%.
“These findings may be useful for clinicians considering postpartum treatment options for patients with MS,” the researchers wrote.
Overall, the data presented at AAN “demonstrate the strength of our portfolio and Biogen’s commitment to enhancing the care of individuals with relapsing MS,” Kieseier concluded.
