More than 20 multiple sclerosis (MS) disease-modifying drugs (DMDs) currently are available in the U.S. But even with all the competition, prices for most of the agents are around $80,000 per year. Following updated professional treatment guidelines and the FDA approval of new therapies, including generics, Prime Therapeutics LLC recently conducted a study to determine spend and use of the agents over a two-year period. Spending for the class remained fairly steady, as generic use helped offset some costs. Payers should encourage use of these products to help contain their spend on this class, maintains a source from the PBM.

All of the drugs in the study are approved to treat relapsing forms of MS, the most common disease course. Only one — ocrelizumab — also is approved to treat primary progressive MS.

Prime presented the findings during the Academy of Managed Care Pharmacy Virtual Annual Meeting in April.

Among Prime’s 15 million commercially insured members, the total plan and member amount paid through medical and pharmacy benefits for MS DMDs was $6.80 per member per month (PMPM) from the third quarter of 2019 to the second quarter of 2020. That makes it the fourth-highest category in spend for the company behind autoimmune, cancer and HIV.

In April 2018, the American Academy of Neurology (AAN) released its updated MS guidelines, which recommend first-line treatment with alemtuzumab, fingolimod or natalizumab for people with highly active disease. According to AAN, “subgroup analyses from phase III pivotal trials of alemtuzumab, fingolimod, and natalizumab showed a reduction in relapses and MRI measures in people with MS with highly active disease. Compared with interferon-β (IFN-β) therapy, treatment with these therapies resulted in more favorable outcomes in the subgroup of people with MS with highly active disease.”

And since October 2018, a handful of novel DMDs have received FDA approval, as have generics for glatiramer and dimethyl fumarate.

The Prime poster notes that while the Institute for Clinical and Economic Review (ICER) released a report in 2017 on MS DMDs’ cost-effectiveness, “it is likely of diminished relevance to payers today given the major shifts that have occurred in MS therapeutics and treatment guidelines since the report’s release. There is a paucity of data to describe the changes in MS DMD spending and utilization, and initial MS DMD treatment selection” following the new products’ approvals and updated guidelines. In order to design formularies and care management programs, payers need to know this data.

For the utilization, spend and trend analysis, researchers analyzed pharmacy and medical claims from July 2018 through June 2020 for Prime’s 15 million commercially insured members to identify claims for alemtuzumab, cladribine tablets, dimethyl fumarate, diroximel fumarate, fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b, mitoxantrone, natalizumab, ocrelizumab, peginterferon, siponimod and teriflunomide. Selected drugs were grouped together as fumarates (dimethyl fumarate and diroximel fumarate), sphingosine 1-phosphate receptor (S1PR) modulators (fingolimod and siponimod) and interferons (interferon beta-1a, interferon beta-1b and peginterferon). They then confirmed that the claims were for MS treatment.

The total paid amount was the sum of insurer and member payments without adjusting for rebates or coupons. Researchers calculated utilization for each MS DMD or DMD group per 100,000 members and reported it quarterly. To get quarterly PMPM cost, researchers divided the total paid amount in a quarter by the average monthly membership in that quarter. PMPM was calculated for each DMD or DMD group and reported quarterly. To assess generic glatiramer use, claims were divided into three groups — Copaxone, Glatopa and other generic glatiramers — and PMPM was calculated for each and reported quarterly.

For the MS DMD new start analysis, the same pharmacy and medical claims from July 2018 through June 2020 were analyzed for dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b, natalizumab, ocrelizumab, peginterferon or teriflunomide. Researchers defined the earliest claim during that time frame as the index date and index drug in each quarter. New starts were those members continuously enrolled for 12 months before the index data and who had no paid DMD claim during that time.

Overall PMPM Rose From $6.93 to $7.05

Researchers found 245,353 MS DMD pharmacy claims and 47,762 medical claims. They removed 1,384 medical claims that had inappropriately low total paid amount and/or billed number of services, while 26 pharmacy claims with a total paid amount of $0 were removed. Mitoxantrone claims were excluded because less than 2% were for MS.

The overall DMD PMPM rose from $6.93 in third-quarter 2018 to $7.05 in second-quarter 2020. In the medical benefit, PMPM increased from $2.09 to $2.41; it dropped from $4.83 to $4.64 in the pharmacy benefit.

Claims per quarter per 100,000 members declined from 85 to 79 during the study period. Medical benefit claims increased from 12 to 13, and pharmacy benefit claims decreased from 73 to 66.

Costs Stayed Steady for All but Two Drugs

For individual drugs, PMPM costs remained fairly consistent except for two: PMPM for ocrelizumab rose 43%, from $1.17 in third-quarter 2018 to $1.67 in second-quarter 2020, and glatiramer declined from $1.14 to $0.65 during the same period of time.

For the analysis of new starts on DMDs, a total of 2,941 new starts were included. New starts for the AAN-recommended natalizumab and fingolimod increased from 12.9% in the third quarter of 2018 to 16.3% in the second quarter of 2020. Natalizumab had more utilization as a first-line treatment than filgotinib did. The highest rates of new starts were for ocrelizumab, dimethyl fumarate and glatiramer acetate agents.

Asked what some of the most interesting findings of the study were, Cathy Starner, Pharm.D., principal health outcomes researcher at Prime Therapeutics, replies that there is no way to comprehensively see MS specialty drug trend without integrated medical and pharmacy drug trend analytics, which “provided insights to understand the overall flat drug trend by showing: The medical benefit drug ocrelizumab (Ocrevus) accounted for 24% of overall MS DMD spend in the second quarter of 2020, and ocrelizumab PMPM spend increased 43% over the two-year analysis period.” However, the decrease in PMPM costs for glatiramer — a subcutaneous injectable on the pharmacy benefit — helped offset the rise in PMPM costs for ocrelizumab — an infusible under the medical benefit — “resulting in flat overall combined medical and pharmacy MS drug spend.” She tells AIS Health, a division of MMIT, that through the first half of 2020, the price of the original glatiramer, Copaxone, was more than double the prices of the generics.

In addition, she points out, “in the second quarter of 2020, 28.5% of MS patients newly initiated treatment with intravenously infused ocrelizumab instead of an oral or other self-administered MS disease modifying therapy.”

Natalizumab New Starts Jumped in 2Q ’20

New starts for the infusible natalizumab jumped from 7.6% in first- quarter 2020 to 12.5% in the second quarter. “By the end of May 2020, states began reopening, and people began to see their providers again,” she says. “The increase in new natalizumab utilizers may have been the result of patients waiting to get their dose until they felt safe and had provider clinic accessibility.”

When asked whether she would have expected claims for natalizumab and fingolimod to have increased more in light of the AAN recommendations, Starner points out that “the latency period between the release of the data used to inform the guidelines and the release date of the guidelines could have played a role in the relatively small increase in natalizumab/fingolimod new starts. Providers working with many MS patients may have been already initiating the more highly active therapies in patients they identified with highly active disease prior to guideline publication (based on their own assessment of the data supporting natalizumab/fingolimod use).”

According to the AAN guidelines, “None of the available DMTs [i.e., disease-modifying therapies] is completely effective against relapses and MRI activity. When a patient shows breakthrough disease activity (continued relapses, MRI activity), trying a medication with a different mechanism or efficacy profile may be beneficial. Although all possible clinical scenarios cannot be answered by drug trials, current evidence supports higher efficacy of alemtuzumab, natalizumab, fingolimod, and ocrelizumab compared with previously approved self-injectable DMTs. Tolerability and likelihood of adherence are other factors that are important in decisions about switching DMTs. Physician judgment and patient preferences are critical in this process.”

What May Be Behind Ocrelizumab Use?

With ocrelizumab the only drug approved for primary progressive MS, could that — or perhaps its twice-yearly dosing — be the reason behind its high use? Starner explains that international classification of disease, ICD-10, codes do not distinguish among the different forms of MS. “The lack of ICD-10 medical claim diagnosis coding differentiating primary progressive MS and relapsing-remitting MS hinders our ability to assign MS type among the individuals. Ocrelizumab to treat primary progressive MS is a potential contributor to the high use; however, we are not able to explore this potential explanation. Dosing convenience and promising data on relapse rate may play a more significant role in the observed trends than the unique FDA indication; however, it is difficult to know for certain in our data.”

If payers wanted to drill down on ocrelizumab use, they could “request attestation from the provider or ask questions of providers that could help them identify MS diagnosis type,” she states. If prior authorization (PA) is required, payers also could use that to identify a person’s diagnosis. “However, frequently different PA systems are used for medical benefit drugs and pharmacy benefit drugs, and not all insured lives have a PA for their MS drugs. Using PA information is potentially a source for more detailed MS diagnosis information.”

One takeaway from the study for payers is the fact that “in 2019, the highest rate of new starts to MS DMDs were ocrelizumab, dimethyl fumarate and glatiramer acetate products,” with the two latter drugs having generics available. “Directing treatment-naive patients to generic and lower cost MS therapies represents a cost-saving opportunity for payers.” Another is that “for a complete understanding of MS DMD drug trends, it is essential for insurers to integrate their pharmacy and medical claims data.”

She states that although the study shows costs for these therapies were flat, ICER found that they are “overpriced in relation to the patient benefits.…With wholesale acquisition cost (WAC) for the vast majority of MS branded drugs at or above $80,000 a year, in just over 12 years of MS branded drug therapy, an individual will incur $1 million in MS drug costs. Using the ICER MS report and further marketplace discounts, Prime has assessed the branded MS drug pricing fairness and found MS drugs still overpriced to value.

“Fair MS drug pricing is at the discretion of the MS drug manufacturers,” she continues. “One way an insurer can obtain fair pricing is through value-based purchasing agreements. Prime Therapeutics has entered into value-based purchasing agreements with some MS drug manufacturers and encourages all manufacturers to provide fair pricing terms.”

Contact Starner through Jenine Anderson at jenine.anderson@primetherapeutics.com.