ICER: Monoclonal Antibodies Not Cost-Effective in Multiple Sclerosis

A potential new monoclonal antibodies therapy for relapsing forms of multiple sclerosis under review at the FDA — ublituximab — as well as all currently available monoclonal antibodies, would have to be discounted by 51% to 84% to be considered cost-effective, according to an updated evidence report from The Institute for Clinical and Economic Review (ICER).

ICER found that these therapies — TG Therapeutics’ ublituximab, Biogen’s Tysabri (natalizumab), Novartis’ Kesimpta (ofatumumab), Genentech’s Ocrevus (ocrelizumab) — will achieve common thresholds of cost-effectiveness if priced between $16,500 and $34,900 per year. In their analysis, ICER analysts assumed a placeholder annual acquisition cost for ublituximab of 55,081, equal to the net price of Ocrevus. The annual acquisition cost for Tysabri is $100,902 and Kesimpta is $87,730.

Jon Campbell, Ph.D.

“Our analysis also found that monoclonal antibodies would need to be priced considerably lower than they are now in order to meet traditional standards for cost-effectiveness,” Jon Campbell, Ph.D., ICER’s senior vice president of health economics, said in a press release.

Ublituximab is anti-CD20 monoclonal antibody that has is currently under review at the FDA; the Prescription Drug User Fee Act action date is Dec. 22, 2022. TG Therapeutics released in August 2022 new exploratory analyses from the ULTIMATE I and II phase 3 trials. Both trials met their primary endpoint with statistically significant reduction in annualized relapse rate over a 96-week period compared with Sanofi’s Aubagio (teriflunomide) in patients with RMS. ULTIMATE I and II demonstrated significant reductions in risk of relapses, as well as reduction of active or new brain lesions.

In a pooled analysis the most common adverse event associated with ublituximab was infusion related reactions (47.7% of patients who received ublituximab experienced at least one infusion-related reaction vs. 12.2% for the teriflunomide group).

ICER analysts found that ublituximab as effective as other monoclonal antibodies at reducing relapses in patients with multiple sclerosis but there was less data to compare changes to confirmed disability progression at six months. Compared with oral products, ublituximab showed a relatively greater reduction in relapses. Based on head-to-head trial data, ICER analysts had higher certainty that ublituximab provides a small net health benefit over Sanofi’s Aubagio (teriflunomide) but they did not have sufficient evidence to rate ublituximab versus Novartis’ Mayzent (siponimod) because of differences in trial populations.

ICER analysts compared ublituximab with several currently monoclonal antibody therapies to treat patients with multiple sclerosis, including Tysabri, Kesimpta, Ocrevus, and Genentech’s Rituxan (rituximab) and its biosimilars.

The analysis also included oral therapies to multiple sclerosis:

• Biogen therapies Tecfidera (dimethyl fumarate) and its generics and Vumerity (diroximel fumarate);
• Banner Life Sciences’ Bafiertam (monomethyl fumarate);
• Novartis therapies Gilenya (fingolimod) and Mayzent (siponimod);
• BMS’ Zeposia (ozanimod);
• Janssen’s Ponvory (ponesimod); and
• Sanofi’s Aubagio (teriflunomide)

ICER used a decision analytic model to assess comparative cost-effectiveness. All treatments had base-case results greater than $150,000 per quality-adjusted life year (QALY) gained and equal-value life year (evLY) gained.

Because the clinical evidence was insufficient to differentiate between the monoclonal antibodies, ICER presented one health-benefit price benchmark (HBPB) range across all modeled monoclonal antibodies (rather than a separate range for each intervention). ICER’s HBPB is a price range suggesting the highest U.S. price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment.

This analysis will be reviewed at a Jan. 20, 2023, meeting.