The U.S. Food and Drug Administration (FDA) has given final approval to Banner Life Sciences’ Bafiertam (monomethyl fumarate), a bioequivalent alternative to Biogen’s Tecfidera (dimethyl fumarate) to treat people with relapsing multiple sclerosis (MS).

Relapsing forms of MS are clinically isolated syndrome (CIS), relapsing-remitting disease (RRMS), and active secondary progressive MS (SPMS).

“The FDA’s final approval marks an important milestone for Banner and for patients living with relapsing-remitting multiple sclerosis,” Franck Rousseau, MD, CEO of Banner, said in a press release. “We are working diligently and are eager to bring this alternative treatment to physicians and patients as soon as possible.”

Bafiertam, a delayed-release capsule treatment, was given tentative approval by the FDA in November 2018, noting it satisfied the bioequivalence, safety, efficacy, and quality standards required for approval. Bioequivalence means that equal doses of two medicines provide the same amount of the active ingredient at the proper site of action.

Final approval was pending the June expiration of a U.S. patent protecting Tecfidera, as well as litigation between Banner and Biogen regarding the patent.

The U.S. District Court for the District of Delaware ruled in favor of Banner in January, deciding that Bafiertam did not infringe upon the patent. This decision was upheld by the United States Court of Appeals for the Federal Circuit in April.

The active ingredient of Bafiertam is monomethyl fumarate. Tecfidera is quickly converted from dimethyl fumarate into monomethyl fumarate in the body. Patients treated with Tecfidera, however, have reported a range of gastrointestinal side effects, such as indigestion, nausea, diarrhea, vomiting, and abdominal pain. 

Banner sponsored a Phase 1 clinical trial (NCT04022473) comparing the gastrointestinal tolerability of Bafiertam to Tecfidera in 210 healthy adults. Participants were randomly assigned to one of the two oral therapies, and followed for five weeks, as gastrointestinal side effects typically appear in the first weeks of treatment.

In the first phase of the study, a titration period, volunteers were given oral capsules of either Bafiertam at 95 mg or Tecfidera at 120 mg (its recommended initial dose) two times a day for seven days. During the study’s four-week second phase, a maintenance treatment period, participants were given either Bafiertam at 190 mg or Tecfidera at 240 mg twice a day.

According to company officials, Bafiertam is expected to cause fewer and less severe gastrointestinal side effects compared to Tecfidera.

“As a practicing neurologist treating patients with MS, I’m encouraged that a lower dose of Bafiertam is equivalent to Tecfidera, and may possibly lead to improved gastrointestinal tolerability for patients, especially early in the treatment regimen,” said Daniel Wynn, MD, director at Consultants in Neurology Multiple Sclerosis Comprehensive Care Center in Chicago.

Bafiertam is not recommended for patients with a known hypersensitivity to Tecfidera or related therapies.

Information on adverse events related to Bafiertam’s use is based on those found in patients taking Tecfidera. The most serious include difficulties breathing and swelling of the throat and tongue, or an opportunistic viral infection of the brain caused by the JC virus (JCV) called progressive multifocal leukoencephalopathy (PML). At a first sign or symptoms of these events, Bafiertam treatment should be stopped and medical care sought. 

In addition to other opportunistic infections, low white blood cell counts and liver injury are also known. Bafiertam may cause flushing, which, based on experience with Tecfidera, generally begins soon after treatment initiation. 

To help ease flush in patients with RRMS, the FDA granted orphan drug status to a new aspirin formulation, called VTS-Aspirin, used in combination with the fumarate-based therapies Bafiertam or Vumerity (diroximel fumarate, also by Biogen) as a potential alternative oral treatment for RRMS. 

Aspirin has been successfully used to ease the side effects of fumarate-induced flushing, but needs to be taken at least 30 minutes before the fumarate treatment to be effective. VTS-Aspirin, being developed by Vitalis, can be taken at the same time as a fumarate treatment, and can be used in combination with approved therapies or as one single medication. 

In a small randomized clinical trial in healthy people, VTS-Aspirin plus Tecfidera was reported to reduce flushing by 63.3% compared to those on Tecfidera alone. It also completely stopped flushing in one-third of participants. 

To support approval of this VTS-Aspirin and new fumarate combination, called VTS-72 by Vitalis, the company announced plans to launch a Phase 3 clinical trial this year.