Disease Analysis: Multiple Sclerosis

Definition

Multiple sclerosis (MS) is widely recognized as the most common neurological and inflammatory disorder of the central nervous system (CNS) in the adult population. It is a chronic, recurrent, progressive autoimmune disorder characterized by repeated episodes of inflammation of the white matter nervous tissue of the CNS. The location of the inflammation varies from person to person and from episode to episode, and as such, results in a variety of clinical symptoms. The periventricular regions, optic nerves, brainstem, cerebellum, and spinal cord are common locations for inflammation in MS. The average age for disease onset is 30 years, with women being twice as likely to develop MS compared to men.

Latest key takeaways

• Datamonitor Healthcare estimates that in 2021, there were 2.1 million prevalent cases of multiple sclerosis (MS) worldwide, and forecasts that number to increase to 2.2 million prevalent cases by 2027.
• A large selection of disease-modifying therapies (DMTs) are currently available in the MS market with a sizable range of attributes, potencies, and safety profiles. Consequently, this set of DMTs typically can yield some relief from this chronic condition.
• Utilization of first-generation DMTs such as Avonex, Betaseron, Copaxone, and Rebif is declining due to their comparatively poor safety, efficacy, and administration profiles versus newer DMTs. Most are genericized, but still see some use in the first-line treatment setting, particularly for less severe cases of MS and especially where payer pressure is involved.
• Since Ocrevus’s launch in 2017, the drug has quickly risen to realize its gold-standard potential in the wider MS field. Its efficacy is unparalleled, and coupled with its six-monthly dosing regimen, the drug is popular with patients and physicians alike. As the only approved therapy for primary progressive MS (PPMS), it has little competition in this patient segment. Furthermore, Ocrevus is increasingly being prescribed at the first and second lines of treatment in other MS subtypes, and particularly in more rapidly progressing and severe cases.
• Long-awaited decisions have been made in key patent litigation trials of former blockbuster DMTs. In 2020, it was ruled that Biogen’s ‘514 patent, protecting Tecfidera until 2028, was invalid. This paved the way for Mylan to gain FDA approval for its dimethyl fumarate generic and launch the drug in rapid succession.
• Novartis’s success in confirming validity for the Gilenya dosing regimen patent, which was set to expire in December 2027 (inclusive of the pediatric exclusivity extension), was short-lived. The Supreme Court reversed a lower court judgment from 2020 which had previously upheld the validity of patent 9,187,405. Following the Supreme Court decision, fingolimod generics have now entered the market.
• Bristol Myers Squibb’s Zeposia, a sphingosine-1-phosphate (S1P) receptor modulator, was approved in 2020 for relapsing forms of multiple sclerosis (RMS), and will provide stiff competition for rival S1P drugs Gilenya and Mayzent. Meanwhile, market penetration may be difficult for Johnson & Johnson’s Ponvory, which was approved in March 2021. As another S1P receptor modulator, the drug lacks a clearly distinguished profile from its rivals.
• Novartis’s anti-CD20-targeting drug Kesimpta has received FDA approval for the treatment of RMS in adults. This positions the drug as a direct market competitor to Roche’s dominant Ocrevus, though Roche has the underserved PPMS segment contained in the Ocrevus label. Kesimpta, however, has the advantage of a more appealing subcutaneous administration route.
• High-impact upcoming events for drugs in the MS space expected before the end of 2022 comprise a US approval decision for ublituximab. In subsequent years, we can expect highly impactful topline results for subcutaneous Ocrevus, as well as Phase III topline results for multiple pipeline agents, such as evobrutinib, IMU-838, and LOU064.