It’s been just over six months since NHS England made cladribine (Mavenclad) available to patients with highly-active relapsing remitting multiple sclerosis (RRMS) in England, but according to a report released by Spherix Global Insights the drug’s “use remains low due to limited access, restrictive guidelines and a resulting lack of prescriber base growth”.
Cladribine is thought to be competing with other drugs, such as Novartis’ Gilenya and monoclonal antibody disease modifying therapies (DMTs) including Roche’s Ocrevus, Sanofi’s Lemtrada and Biogen’s Tysabri, for patients.
It is interesting to note that, potentially in anticipation of the March market withdrawal of Biogen's Zinbryta, some current Mavenclad-treated patients were switched from Zinbryta, especially in Germany where neurologists are more likely to see Mavenclad displacing Zinbryta than other DMTs.
Ocrevus was approved in January 2018 for RRMS and early primary progressive MS (PPMS) and has experienced a vastly different initial European Union (EU) launch due to broad use across the five EU countries even in advance of national pricing and reimbursement decisions in many counties. One month post-launch, the Ocrevus prescriber base and self-reported share has surpassed that of Mavenclad. Compared to neurologists in Germany and the United Kingdom (UK), neurologists in Italy and Spain report a greater Ocrevus trial rate, share, and patient volume per neurologist supported by the availability of local compassionate use programs in response to the high unmet need in PPMS.
Neurologists in the UK, with the lowest current prescriber base and most limited access, are pessimistic about payer restrictions for Ocrevus. This is perhaps in reaction to the recent NICE draft guidance for routine funding for Novartis' Extavia, which may be putting other DMTs, such as the interferons and Teva's Copaxone, at risk for reimbursement. Indeed, while current access through non-formulary channels will be beneficial for increasing neurologists' familiarity and comfort with Ocrevus, transitioning these patients from the compassionate use programs to country-level health plans may present a discontinuation pressure point due to potentially restrictive guidelines and out-of-pocket cost for patients.
In contrast to the early US launch, only around one-third of Ocrevus-treated patients in the EU are diagnosed with RRMS (compared to 54% one month post-launch in the United States). Slower uptake within RRMS, the MS subtype with the largest number of patients, may suppress Ocrevus maximal share especially with EU neurologists' lower expectations of regulatory authorities finding added benefit in RRMS compared to PPMS.
In the EU, Novartis is positioned to challenge Biogen for the MS market leadership position based upon current manufacturer support perceptions and an appealing MS pipeline. While more than two out of five neurologists currently select Biogen as the manufacturer offering the best overall support to their clinical practice, Novartis is a close second and both companies are frequently selected for best overall support to patients. Novartis has carved out their current position with just two marketed DMTs (Extavia and Gilenya) and two late-stage DMTs in the pipeline: siponimod, a next-gen S1P receptor modulator filing in Q3 2018 for the first broad SPMS label, and ofatumumab, a human anti-CD20 therapy that will be the only subcutaneous mAb DMT following the recent withdrawal of Zinbryta. With the majority of neurologists selecting one of these two Novartis products as the pipeline DMT they are most interested in having available, successful launches over the next three years could shift the competitive dynamic in favour of Novartis.