One of the first multiple sclerosis (MS) drugs to win approval from the U.S. Food and Drug Administration (FDA) just got a makeover and will be hitting the market as a twice-monthly injection called Plegridy.
A research team led by Dr. Peter Calabresi, a professor of neurology at the Johns Hopkins Medicine and director of the university's Multiple Sclerosis Center, showed that interferon beta 1a could be modified to create a long-acting version of the drug, which only needs to be injected twice a month.
Betaseron, Avonex, and Rebif all fall under the umbrella class of "interferon beta." Further classification separates Betaseron, which is known as interferon beta 1b, from Avonex and Rebif which fall under the heading of interferon beta 1a. Avonex is administered by intramuscular injection once a week, and Rebif is taken three times per week using a smaller needle, and is injected into the fatty layer under the skin.
Calabresi and his team set out to modify the interferon beta 1a drug Avonex.
Cosmetics Ingredient Is Key to the Drug's Lasting Effects
For the experiment, Calabresi enlisted more than 1,500 people with MS and divided them into three groups. One group received a placebo shot every two weeks, another was given the modified interferon beta 1a every two weeks, and the third group received the modified medicine once a month, with a “dummy” shot at the two week mark in between. The study was “blind,” meaning the patients all took shots every two weeks but nobody knew to which group they had been assigned.
Calabresi and his team were hoping to learn whether the new version of the drug would be more effective if taken every two weeks or once a month.
In order to give the interferon a more lasting effect, scientists added “polyethylene glycol (PEG) polymer chemical chains,” according to a press release. “PEG has been proven safe in other medications, shampoos, toothpaste, and moisturizers.” According to the National Institutes of Health, PEG is also used as a laxative and is the active ingredient in MiraLax.
Adding this ingredient, Calabresi told Healthline, "decreases metabolism/degradation of protein so it has a longer half-life." That makes a single dose of the drug last much longer. Although there are no side effects of using PEG, Calabresi said it "may increase interferon potency, [increasing the] toxicity of the drug, but [there are no known side effects] related to PEG itself, which is in many cosmetic products."
Their results showed that the new, modified version of interferon beta 1a worked best when taken every other week. And the patients in the study did not develop resistance to the drug when tested at the end of one year.
Many patients who are given an interferon drug for MS will, over time, develop antibodies to fight the drug and it will become less effective for them. When that happens, patients have no alternative but to try other drugs or therapies to slow their disease progression.
At the end of Calabresi’s study, the group given the twice-monthly interferon beta 1a shots fared best. Their annual relapse rate diminished by 36 percent and magnetic resonance imaging (MRI) scans revealed a dramatic 67 percent drop in new, enhancing MS lesions.
'A Huge Advantage' for MS Patients
Though the latest trend in MS drugs is to administer them in pill form, there is good reason to revisit the less sexy—yet tried and true—injectables.
Interferon beta has a long-standing track record, with 20 years of post-marketing data to support its safety, tolerability, and effectiveness. A modified version with a less frequent dosing schedule gives people with MS yet another weapon for their disease fighting arsenal.
"While this isn't a brand new blockbuster drug, I do think it will improve compliance and tolerability and therefore positively impact the quality of life of people with MS who take interferon beta," said Calabresi in the press release. "If it gets FDA approval, this new formulation would allow patients to get the same effect, but instead of the burden of injecting themselves every other day, they only have to do it twice a month. For an MS patient, that's a huge advance."
When asked how soon this new version might hit shelves, Calabresi said that the "FDA is said to make a decision in August, but they sometimes delay these dates."
Correction: A previous version of this story stated that the drug Rebif is being re-engineered. In fact, Avonex is the drug in question. Also, Rebif is taken by injection three times per week, not every other day.