In early April 2017, Roche/Genentech launched its hotly-anticipated anti-CD20 monoclonal antibody Ocrevus (ocrelizumab) for the treatment of relapsing forms of MS (RMS) and—in a landmark FDA approval—primary progressive MS (PP-MS). In short, Ocrevus depletes CD-20 positive B cells and offers superior efficacy in RMS compared with Rebif (interferon-β-1a, subcutaneous delivery) while exhibiting a compelling safety profile in two Phase III trials [OPERA I and II]. Excitingly, in PP-MS, data from the Phase III trial [ORATORIO] show that Ocrevus slows disease progression compared with placebo. DRG is preparing to field a three-wave launch-tracking series on the drug in both patient subtypes* to learn, “in real time,” how quickly neurologists adopt Ocrevus and how they incorporate the product into the MS treatment algorithm. These findings will help us further refine our forecasts. Here, we offer some thoughts and perspectives on Ocrevus and its potential impact on both populations, each distinct in its issues and considerations.
Separating risk from efficacy in relapsing MS? Ocrevus is the 15th disease modifying therapy (DMT) approved for RMS; it’s a crowded market, increasingly shaped by oral agents but with a durable reliance on platform injectables (owing to time-tested safety) and arguably underpenetrated by the most effective options. The fanfare for Ocrevus is justified. The drug is poised to be a game-changer where other highly-potent agents (e.g., Tysabri and Lemtrada) were not due to its favorable safety profile. Ocrevus’s label is impressively clean with no line of therapy guidance, no REMS, and no specified monitoring protocol. Warnings that do appear are not unexpected and include infusion-related side effects (the most common adverse events in clinical trials), malignancy risks (an imbalance of cases was observed in clinical trials between treatment groups), and mechanism of action-related progressive multifocal leukoencephalopathy (PML) risk. However, none appear as black box warnings and no cases of PML have been observed with Ocrevus to date. Ocrevus’s uptake, as for any new DMT, ultimately hinges on its acceptance by a generally risk-averse prescriber base (though one growing increasingly accustomed to managing risk). At this time, we expect the Ocrevus adopter pool for RMS patients will grow rapidly, but total volume may grow at a more cautious pace overall (which we will examine with our launch-tracking series). DRG interviews with experts (before approval) indicate the existence of anticipation and a readiness among “aggressive treaters” to integrate the drug immediately into practice. (In fact, one expert interviewed on April 28th confirmed that “warehousing” of patients for Ocrevus has been occurring, and stated that approximately 30 patients had already been infused.) This, coupled with early demand from existing suboptimal responders, could mean a solid initial uptake in second or later lines of therapy in relapsing patients who are ready to switch therapies. We expect deeper penetration to occur over time as post-market experience builds, more so if the drug can encroach into earlier lines of therapy—which would be in line with growing consensus in the field, but not prevailing practice, that early treatment with more-potent therapies optimizes long-term outcomes. In the words of one U.S. expert interviewed, “There is absolutely a first-line role for Ocrevus in relapsing MS; there are centers that use rituximab as a first-line drug in JCV-positive patients, and Tysabri in seronegative patients; these are aggressive treaters. I would use rituximab more in my practice if I could, but insurance coverage is limiting. Aggressive docs will contend that Ocrevus is a first-line drug for all MS patients, conservative ones will say none. It’s a powerful drug and patients will have to accept that they are on a ‘big gun.’ Ultimately, I think Ocrevus will take some of the new diagnoses for the bold treaters, it will take a lot of the Tysabri patients, and it will take the breakthrough disease activity patients on Tecfidera and Gilenya.”
Our take on Ocrevus in PP-MS: DRG research has repeatedly shown that patients with PP-MS, when they are treated with DMTs, receive off-label DMTs in roughly the same pattern as their relapsing counterparts, with perhaps greater reliance on more potent drugs or therapies outside the MS drug basket. As such, Ocrevus, which secured breakthrough therapy designation from the FDA, is long-awaited and is much needed in this population. DRG primary market research conducted in February 2017 indicates that two-thirds of surveyed neurologists anticipate prescribing Ocrevus to their PP-MS patients. However, among likely prescribers, the mean maximum patient share they project for Ocrevus in PP-MS falls meaningfully below 100%. We will probe this intriguing finding in our launch-tracking series as we seek to better identify the profile of the PP-MS patient who is likely, and is not likely, to receive this first and only approved therapy for PP-MS. In an interview earlier this month, a U.S. expert suggested that it would be difficult for physicians to deny a PP-MS patient’s request to initiate Ocrevus treatment since it is the only approved therapy available for this patient population. Additionally, we have previously shared some thoughts on Ocrevus use in PP-MS patients in another forum (click here).
That price point: Understandably, much has been made of the annual cost of Ocrevus. At $65,000/year (wholesale acquisition cost [WAC]), the drug becomes one of the most competitive products in the market, alongside Sandoz/Momenta’s Glatopa (the only generic DMT available) at $63,000/year. This is in sharp contrast to the last MAb to reach the market, Zinbryta, which launched at a price of $82,000/year, more in line with other U.S. DMTs. The U.S. MS market has been subject to steep pricing increases year-over-year and a premium price point for Ocrevus would not have been a shock (in fact, it was our forecast expectation) given its compelling clinical value. However, the drug’s potential to grow the market by increasing drug-treatment rates (especially in PP-MS) and bringing DMT abandoners back to treatment permits a more judicious pricing approach. Roche/Genentech’s strategy stands out at a time where the pharmaceutical industry at large has attracted ample scrutiny surrounding pricing. Indeed, Genentech stated that pricing Ocrevus in this manner is an “important first step” in addressing industry pricing trends.
Ocrevus also stands to win over payers: earlier this year, the Institute for Clinical and Economic Review (ICER) published an evidence report1 that included Ocrevus in its value assessment with hypothetical outcomes. According to the report, Ocrevus may come close to achieving ICER’s cost per QALY threshold in relapsing forms of MS; in order for Ocrevus to achieve a willingness to pay (WTP) threshold of $150,000/QALY, it would have to be priced at approximately $58,600. (Note that the drug would exceed ICER’s cost per QALY threshold for PP-MS if priced above $14,367, perhaps because ICER compared the drug to best supportive care in its PP-MS analysis.) Harkening to the point raised by Merck KGaA in its response to the buzz surrounding Ocrevus’s price relative to Rebif, Ocrevus could be covered on a medical benefit (vs. a pharmacy benefit) and be subject to lower discounting. That said, DRG’s national formulary data indicate that a sizeable proportion of plans cover Tysabri and Lemtrada (both infusibles) as a pharmacy benefit, and we might expect the same for Ocrevus. In either coverage situation, it appears the drug is set to offer a competitive net price to payers, and a similar pricing strategy may set up the drug favorably for payer negotiations in Europe, where the drug is under EMA review. As we refine our forecast to take a different WAC and an unrestrictive label into account, we continue to anticipate Ocrevus will achieve multi-billion-dollar sales through 2025, even as a subcutaneous next-generation competitor from Genmab/Novartis is projected to enter the market of relapsing forms of MS in 2020.
*DRG will be following prescribing trends of Ocrevus in PP-MS and relapsing MS to providing in-depth analysis through three waves of Emerging Therapy reports. In addition, DRG will release an Access and Reimbursement (US) report that covers neurologists’ and managed care organizations’ perceptions of the MS market and addresses potential uptake and formulary placement of Ocrevus and other future entrants.
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- Disease-Modifying Therapies for Relapsing-Remitting and Primary-Progressive Multiple Sclerosis: Effectiveness and Value, March 6, 2017.