The FDA granted approvals to HEC Pharm Co. Limited, Biocon Limited, and Sun Pharmaceutical Industries Limited, for their generic formulations of Novartis’ product, branded as Gilenya, for the treatment of relapsing forms of multiple sclerosis.
Janet Woodcock, MD
The FDA has approved the first 3 generic formulations of fingolimod (Gilenya; Novartis) for the treatment of relapsing forms of multiple sclerosis (MS).1
The approvals were granted to HEC Pharm Co. Limited, Biocon Limited, and Sun Pharmaceutical Industries Limited. Novartis’ formulation of fingolimod was first approved for this indication in September 2010 as the first oral treatment for MS, and was additionally approved for the treatment of children and adolescents aged 10 years and older with relapsing MS, making immunomodulating drug the first agent specifically approved to treat MS in pediatric patients.
“Approving safe and effective generics so patients have more treatment options continues to be a priority for the FDA,” Janet Woodcock, MD, director, Center for Drug Evaluation and Research, FDA, said in a statement. “Having access to affordable treatments is important for patients with conditions that require ongoing care. The FDA has a longstanding commitment to increasing patient access to lower-cost, high-quality generic medicines.”
The treatment was originally approved based on data from the FREEDOMS trial and TRANSFORMS trials, which showed benefit with fingolimod compared to placebo and interferon beta, respectively, in reducing relapse rates and new or enlarging lesions on magnetic resonance imaging (MRI). FREEDOMS also revealed a lower risk of progression of disability with fingolimod compared to placebo after 24 months of follow-up.
According to the FDA, the most frequent adverse events (AEs) reported by patients taking fingolimod in clinical trials included headache, influenza, diarrhea, back pain, elevation of liver enzyme levels, and cough.
In November 2018, the FDA issued a safety alert related to the halting of therapy with fingolimod, stating that the condition can become much worse when treatment is stopped in comparison to while it was being taken or when it was first started.2 This worsening, the agency warned, is rare but may lead to permanent disability. The agency recommended that health care professionals inform their patients before starting treatment about the potential risk of a severe increase in disability after stopping fingolimod.
Additionally, the FDA suggested that health care professionals carefully observe patients for evidence of an exacerbation of their MS and treated appropriately when fingolimod is halted and advise patients to seek immediate medical attention if they experience new or worsened symptoms of MS after fingolimod is stopped. Additionally, they recommended testing for new or enhancing lesions by MRI if an increase in disability occurs and begin appropriate treatment as needed.
Lauren B. Krupp, MD, of NYU Langone Health, told NeurologyLive in August that “the availability of an oral agent has made a huge difference. It also has brought to light how relatively ineffective the interferons were.” This, she said, raised the awareness of high and early efficacy treatment as a very advantageous approach to treating MS.
“The benefit of preventing relapses, of preventing enhancement in terms of enhancing lesions, preventing new lesions, is so important in terms of the well-being of our patients. Some of that is immediate,” Krupp explained. In that same conversation, Brenda L. Banwell, MD, noted that her only concern with the therapy was adherence—as is the case for many medications.
“Just because fingolimod is a tablet does not make it safer than other medications,” Banwell said. And that’s a reminder I give every family. It looks like it is easier to take, but that doesn’t reduce the responsibility for monitoring its safety. And that’s something that we, as an entire community, need to be careful of.”
Although, despite these concerns, some studies have suggested its oral form may increase adherence. A subgroup analysis from a phase 4 trial of fingolimod revealed that the therapy is associated with better treatment adherence with African-American patients. In the trial, African-American patients with MS that were given the oral fingolimod 0.5 mg/day were more 50.2% more likely to remain true to their treatment regimen than those who were treated with injectable disease-modifying therapies (DMTs).3 As well, this was consistent with the findings of the full study cohort, which found that 81.3% of patients given fingolimod were retained compared to 29.2% of those on injectable DMTs (P <.0001).4
1. FDA approves first generics of Gilenya [press release]. Silver Spring, MD: FDA; Published December 5, 2019. fda.gov/news-events/press-announcements/fda-approves-first-generics-gilenya. Accessed December 5, 2019.
2. FDA. Gilenya (fingolimod): Drug Safety Communication - Severe Worsening of Multiple Sclerosis After Stopping the Medicine. FDA website. Published November 20, 2018. fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm626264.htm. Accessed December 5, 2019.
3. Cascione M, Tenenbaum N, Wendt J, et al. Treatment retention on fingolimod compared with injectable multiple sclerosis therapies in African-American patients: A subgroup analysis of a randomized phase 4 study. Mult Scler Relat Dis. 2018;25(1):50-56. doi: 10.1016/j.msard.2018.07.014
4. Cree BA, Arnold DL, Cascione M, Fox EJ, et al. Randomized phase 4 study of retention on fingolimod vs injectable multiple sclerosis therapies. Ther Adv Neuro. Disord. 2017;11:1-15. doi: 10.1177/1756286418774338.