As it enters the market, Ocrevus (ocrelizumab) is a drug set not only to top the multiple sclerosis (MS) field, but also to be 2017’s biggest future-blockbuster entrant. Developed by Roche with involvement from Biogen, the B-cell-targeting antibody is forecast to see annual sales of more than $4 billion by 2023, putting it ahead of previous MS market leaders Copaxone (glatiramer acetate; the first non-interferon to enter the market) and Tecfidera (dimethyl fumarate, which had the fastest market uptake in the field). Enabling Ocrevus to attain this position is its novelty of indication, high efficacy, convenient dosing, reasonable safety and modest pricing.
Targeting an unmet need
MS affects approximately 2.5 million people worldwide and is one of the most common causes of neurological disability in young adults. MS most commonly follows a relapsing-remitting course (RRMS), for which there are a number of approved treatment options including interferons, non-interferon injectables and oral agents. However, Ocrevus is the first drug approved for primary progressive MS (PPMS), a form of the disease that is progressive from the onset and which accounts for approximately 15% of MS cases. The drug’s approval is also not limited to that subset as it is additionally indicated for relapsing MS (RMS). This incorporates both RRMS and also patients with relapses as part of secondary progressive MS (SPMS). Approximately 60% to 70% of RRMS cases become SPMS with time, and there are very limited treatment options available for this form of the disease. By treating relapsing SPMS and PPMS, Ocrevus targets two poorly served MS patient populations as well as RRMS. In addition to its recent U.S. approval, the drug is currently under review in the E.U., with approval and launch expected later in 2017.
Ocrevus gained FDA approval in March 2017 based on impressive phase III data from the OPERA I and OPERA II studies in RMS and the ORATORIO trial in PPMS. In RMS, Ocrevus versus Rebif (recombinant interferon beta-1a) reduced the annualized relapse rate at 96 weeks (46% and 47% in OPERA I and II, respectively), reduced disability progression risk (43% and 37%, respectively), reduced new brain lesions (77% and 83%, respectively) and reduced the number of T1 gadolinium-enhancing lesions (94% and 95%, respectively). In PPMS, Ocrevus versus placebo reduced the risk of confirmed disease progression by 24%, reduced the volume of brain hyperintense T2 lesions (-0.39 versus +0.79 cm3) and reduced (by 25%) the risk of a 20% worsening of the timed 25-foot walk assessment.
Although Ocrevus is an intravenously infused drug competing against many oral options, its superior dosing frequency is likely to more than offset this. Compared with leading oral agents Tecfidera, Gilenya (fingolimod; the first oral MS drug on the U.S. market) and Aubagio (teriflunomide), which are dosed between one and three times daily, Ocrevus is dosed just once every 6 months. This also compares extremely favorably against subcutaneously injected agents such as Copaxone (daily or three times a week depending on the formulation) and Zinbryta (daclizumab; once a month), and intravenous Tysabri (once every 4 weeks).
Tolerable side effect profile
Safety is an issue that has beset the MS field. Tysabri (natalizumab) carries a black box warning regarding its association with fatal progressive multifocal leukoencephalopathy (PML), which occurs at a rate of about 3.5 confirmed cases per 1,000 people treated. Tecfidera and Gilenya also carry label warnings, although not black-boxed, regarding PML, plus further warnings regarding the risk of liver injury. Rebif carries a similar liver warning, while Zinbryta’s liver warning merits a black box, as does its association with immune-mediated disorders. Aubagio carries a black box warning regarding the risk of liver injury and teratogenicity. In contrast, Ocrevus carries no black box and no warnings of specific association with PML or liver injury, although it remains to be seen whether real-world experience will confirm this. Infections and infusion reactions are the most common side effects, although rates of serious infections/adverse events were similar to Rebif or placebo in the OPERA and ORATORIO trials. However, a higher malignancy rate was seen with Ocrevus versus placebo in the ORATORIO study, and this potential risk features on the drug’s label and may be a barrier to uptake.
Ocrevus is priced at $65,000 per year, which is a 25% discount on Rebif and an almost 20% discount on the market average for an MS drug. The U.S.’s National MS Society praised the pricing, and its president, Cyndi Zagieboylo, described the drug as “a real game changer.”
Ocrevus is not the only upheaval facing the MS market – a field that has already seen its share of changes. The entry of oral agents into a previously injectable-only treatment paradigm changed MS treatment significantly. Gilenya was the first to enter in 2010, but although Tecfidera was the third oral to debut, after Aubagio and more than two years after Gilenya, it soon captured market share, benefiting from Gilenya’s need for ECG, blood, vision and liver monitoring at the start of dosing, plus lingering side effect concerns, and from Aubagio’s safety issues and more limited efficacy. Tecfidera almost hit blockbuster status in its first year of launch with sales of $876 million in 2013, tripling to $2.909 billion in 2014, reaching $4.000 billion by 2016 and taking the lead spot in the MS market from Copaxone.
New drugs are also in development against which Ocrevus may have to compete in the future. One example is MedDay’s biotin formulation, MD-1003, which showed good efficacy in a phase II/III trial for not-active progressive disease. Novartis’s siponimod is in development for SPMS, and recently met its phase III trial endpoint. Generics are also a challenge that Ocrevus, and the MS market as a whole, will face. Generic versions of once-daily Copaxone entered in the U.S. and E.U. in 2015 and 2016, respectively, but have not disrupted the market significantly. However, the first generic versions of the oral agents are expected in the short term, with Strides’ generic Gilenya expected to enter in February 2019, which is set to have a much greater impact. It remains to be seen how Ocrevus will fair against cheaper oral alternatives but as of now, Ocrevus with its broad MS label, impressive results, convenient dosing, no black box warning and competitive price is set for maximum impact in the MS market.
The 2017 edition of the annual Drugs to Watch report forecasts that seven other new drugs in addition to Ocrevus will enter the market in 2017 and achieve blockbuster sales of >$1 billion by 2021, as evaluated by consensus sales forecast data from Clarivate Analytics Cortellis Competitive Intelligence (source Thomson Reuters I/B/E/S).
This article is a Clarivate Analytics Market Insights report, an ongoing series featuring expert reviews of hot topics in the pharma/biotech field, with analysis and discussion on the factors currently affecting the industry.