Roche’s Ocrevus had been growing comfortably as the top choice for new multiple sclerosis patients without major concern over competition until Novartis launched an in-class rival, Kesimpta. Now, Roche hopes more data in newly diagnosed patients can help safeguard its lead.
Ocrevus helped 85% of patients with early relapsing-remitting MS erase all evidence of disease activity after 48 weeks of treatment, according to phase 3b data published at the American Academy of Neurology (AAN) annual meeting. That means those patients had no relapses, worsening of disability or new brain lesions.
The entire group on average experienced a very low annualized relapse rate of 0.005. Patients also showed a slight improvement on a disability score called the Expanded Disability Status Scale from 1.71 at baseline to 1.56 after 24 weeks and 1.55 after 48 weeks. A marker of nerve cell damage also returned to near-healthy levels with Ocrevus.
The results came from an open-label, single-arm phase 3b trial dubbed Ensemble. Patients enrolled had never received any prior disease-modifying therapy and had had MS symptoms for less than three years before the screen.
“There has been a recent paradigm shift as data continues to suggest that high-efficacy therapies given early in the disease course may offer the greatest impact in delaying disability progression,” Roche's Genentech said in a statement.
RBC Capital Markets analysts made a similar observation, saying in a recent note that the most efficacious therapies, such as Ocrevus, are being deployed much earlier in the disease “with the idea that you can benefit patients most by hitting MS 'hard and early' and preventing cumulative neurological damage.”
New patients are exactly whom Novartis is targeting for its follow-up analysis of Kesimpta data. At the ECTRIMS event last year, Novartis unveiled a post-hoc analysis of the phase 3 Asclepios I and II trials of Kesimpta in a subgroup of treatment-naïve patients who were exactly the type enrolled in Ocrevus’ Ensemble study.
Compared with Sanofi’s Aubagio, Kesimpta halved the annualized relapse rate; patients on Kesimpta had roughly 0.09 relapses a year, versus 0.18 for Aubagio. At the one-year mark, 47% of Kesimpta patients had no evidence of disease activity, compared with 24.7% of patients for the Aubagio group.
In an update of its post-hoc analysis of the Asclepios trials at the AAN event, Novartis showed Kesimpta cut the risk of disability progression independent of relapse activity by nearly 60% against Aubagio in the newly diagnosed patient subgroup. Over half the cases of confirmed disability worsening in these patients happened regardless of whether they experienced relapse, according to Novartis, indicating MS progression starts fairly early—all the more reason to begin treatment early.
Both Ocrevus and Kesimpta target the CD20 antigen on B cells. Ocrevus is given intravenously by a healthcare practitioner every six months in the maintenance phase, while patients self-administer under-the-skin Kesimpta at home once monthly during maintenance. To further boost its convenience, Ocrevus in December snagged an FDA nod for a shorter, two-hour infusion time, down from the previous 3.5 hours.
Ocrevus also showed a high level of compliance in a real-world analysis of data from U.S. commercial and Medicare and Medicaid claims databases unveiled at AAN.
About 80% of patients adhered to twice-yearly dosing of Ocrevus after their second year of treatment. That was compared with 54% for other IV drugs, 35% for intramuscular and under-the-skin injectables, and 55% for orals. The results were pooled from patients who started treatment between April 2017 and December 2019, so they didn't include any COVID-19 effect or data from Kesimpta, which the FDA approved in August 2020.
Among the many MS treatments out there, Ocrevus maintained a leading U.S. new patient share of 40% as of the end of 2020, according to Roche. The company is also testing a higher dose of the drug in phase 3b trials in relapsing MS and primary progressive MS.
Despite enthusiasm around its convenience, the initial uptake of Kesimpta appears to be slow. A director at one of the nation’s largest academic MS centers said he only started 5% to 10% of his new patients on Kesimpta. That's despite what should be a dosing benefit, with Kesimpta's self-administration helping patients avoid healthcare visits during the pandemic, RBC's analysts noted in their report.
The industry expert suggested the low use of newly launched Kesimpta reflects a tendency among physicians to stick with the drugs they’re most familiar with during the pandemic. Once the crisis passes, the expert expects Kesimpta use to tick up.