Quite a bit’s going on in the world of disease modifying therapies (DMTs), and we’ve prepared a brief update for you. Read on for more about Gilenya’s FDA approval for use in kids, new results from a study on siponimod, daclizumab’s removal from the market, and new data on cladribine.
Gilenya Approved by FDA as First Disease Modifying Therapy for Children with Relapsing MS
Gilenya (fingolimod) has been approved by the U.S. Food and Drug Administration (FDA) to treat children and adoclescants with relapsing forms of MS. Gilenya was previously indicated for adult patients (18 or older), and this expanded approval allows the drug to be used to treat patients with relapsing MS at the age of 10.
The FDA’s approval was supported through the research and outcome data from the Phase 3 PARADIGMS study which compared safety and effectiveness of Gilenya to Avonex in children. The study’s co-principal investigator is Brenda Banwell, MD, the chief of the division of Neurology at Children’s Hospital of Philadelphia. The study, which is ongoing, involved 215 pediatric MS patients, between the ages of 10 and18 at 87 sites across the world.
The participants each took an injection weekly and an oral pill daily. Half of the enrolled participants received active Avonex while the other half of the participants received active fingolimod. The data showed that Gilenya treatment could reduce by nearly 82% the frequency of MS exacerbations in pediatric patients; reduced the development of new brain lesions by 53.4%; and reduce by 77.2% the risk of three-month confirmed disability progression compared with Avonex.[su_blockquote cite=”Dr. Teri Schreiner, RMMSC @ CU”]The importance of this study cannot be underestimated. Those of us treating children and adolescents with multiple sclerosis have used the same disease modifying treatments without data about how the medications work in those patients under 18 years old. Now, we have data and an understanding of how this medication works in the younger population of patients. [/su_blockquote]
The most commons side effects of Gilenya in children were similar to those reported in the clinical trials with adult patients, including upper respiratory tract infections, fever, and an increase susceptibility to the flue and flu-like illnesses.
Siponimod Phase 3 Clinical Trial Results
Results of a Phase 3 clinical trial studying siponimod were recently published in the journal The Lancet. The results showed a reduction of the risk of disability progression in patients with secondary progressive multiple sclerosis (SPMS). The EXPAND trial included 1,651 SPMS patients in 31 countries. Participants had moderate disability and were randomized to either receive 2 mg of siponimod orally or a placebo once a day.
The findings of this study were as follows:[su_list icon=”icon: circle” icon_color=”#193aea”]
- Siponimod reduced participants’ three-month disability progression scores by 21% and six-month scores by 26%, when compared to the placebo.
- Siponimod slowed patients’ brain shrinkage by 23 percent compared with a placebo, and reduced by 55 percent patients’ annualized relapse rate after two years.
- Siponimod reduced by 80 percent the progression of brain lesions.
- Some adverse events were more frequent in siponimod-treated patients than in the placebo group, including lower levels of immune cells in the blood, higher levels of liver enzymes, slower heart rates, high blood pressure, and varicella infections.
Novartis, the maker of this agent, plans to submit an application for siponimod to the U.S. Food and Drug Administration to seek its approval as a disease-modifying therapy for SPMS.
“This would be the second drug approved in this class, with the first being fingolimod (Gilenya),” said Dr. Timothy Vollmer, RMMSC Medical Director and Co-Director of RMMSC at CU. “This being the first to succeed in a secondary progressive patient population will be a welcomed addition to our treatment choices for MS patient of all forms of MS.”
Daclizumab (Zinbryta) Voluntarily Taken Off Market Due to Growing Safety Concerns
As you may have heard, the pharmaceutical companies Biogen and Abbvie have voluntarily taken daclizumab (Zinbryta) for treatment of relapsing MS off the market worldwide. The companies announced that the decision was due to growing concerns about the safety of the drug, including severe liver damage and immune-related conditions. The March announcement came after seven cases of serious inflammatory brain disorders in Germany, including encephalitis and meningoencephalitis, and one case in Spain.
The drug had been approved by the FDA in May, 2016. Biogen and AbbVie say they will continue to work collaboratively with regulatory authorities with healthcare providers who have patients using the drug in the withdrawal of Zinbryta. Patients currently treated with Zinbryta should contact their healthcare provider.
New Data on Cladribine Tablets Released
Results of a study on the effects of cladribine tablets on patients with highly active relapsing MS were published this month in the Multiple Sclerosis Journal. The results showed positive clinical and MRI results in participants with highly active relapsing MS who were given cladribine tablets compared with the placebo.
The study contributed additional data to a prior study on cladribine, called the CLARITY study. This trial involved 870 patients who were placed in different subgroups based on criteria on the level of their disease activity and whether or not they were currently on a disease modifying therapy. The findings of the study were as follows:[su_list icon=”icon: circle” icon_color=”#193aea”]
- In the overall population, cladribine tablets 3.5 mg reduced the risk of 6-month confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs. placebo.
- In the subgroup with a high rate of disease activity (more than 2 relapses in the year prior to the study), there was a risk reduction of 82% vs. the placebo.
- In the subgroups with non-high rate of disease activity, either on DMT or not on DMT, the risk reduction was 18% and 19% respectively.
- This indicates a greater responsiveness to cladribine tablets 3.5 mg in patients with high disease activity.
Cladribine is an oral therapy used as an anti-cancer drug – it works by selectively targeting immune cells thought to be linked to MS. It is approved for use in relapsing MS in Europe and Canada but has not been approved in the United States.