Ozanimod Capsules: Indications Beyond Multiple Sclerosis

Additional Indications Under Investigation

Based on the available information, Ozanimod is currently being evaluated for use in two major inflammatory bowel diseases:

1. Ulcerative colitis (UC)
2. Crohn's disease

Both of these indications are being investigated in multinational phase III trials. This represents a significant expansion of Ozanimod's potential therapeutic applications beyond its initial approval for relapsing forms of multiple sclerosis by the US FDA in March 2020.

It's worth noting that Ozanimod has already achieved a milestone as the first S1P-receptor modulator approved for the treatment of ulcerative colitis. This suggests that while trials are ongoing, there has been some regulatory success for the UC indication.

Mechanism of Action in Inflammatory Bowel Disease

Ozanimod's potential effectiveness in these conditions stems from its mechanism as a sphingosine 1-phosphate (S1P) receptor modulator. It functions as a functional antagonist that causes internalization of S1P receptors on T-cells. This action:

• Inhibits lymphocyte egress from lymph nodes
• Curtails migration to sites of active inflammation

As an oral small molecule with a rapid onset of action, Ozanimod offers a novel therapeutic mechanism in the treatment of UC. Clinical evidence indicates it is an effective treatment for ulcerative colitis patients who are both bio-naïve and bio-exposed.

Intervention Models for Non-MS Trials

Regarding the specific intervention models being utilized in these phase III trials for ulcerative colitis and Crohn's disease, the available information does not provide details about:

• Randomization methods
• Blinding procedures
• Specific study designs
• Control mechanisms

While we know these are multinational phase III trials, the specific design and methodology details are not described in the provided information.

Safety Considerations

Although the safety profile of Ozanimod in ulcerative colitis appears favorable based on current data, it's noted that more long-term data are needed. Additionally, further studies are required to compare Ozanimod to currently available therapies to best define its positioning in UC treatment algorithms.

Ozanimod represents an important development in the treatment landscape for inflammatory bowel diseases, offering a novel mechanism of action and the convenience of oral administration for conditions that significantly impact patients' quality of life.

Economic Burden of Multiple Sclerosis in USA and Europe

United States

The total economic burden of MS in the USA in 2020 was estimated at $20,103.49 more per patient compared to those without MS. Direct healthcare costs can average $70,000 a year and have risen rapidly over the last decade. Disease-modifying therapies (DMTs) are the major cost contributors, accounting for 43%-78% of direct costs, with the median annual price for branded DMT products currently exceeding $90,000.

Prescription medication expenditures accounted for 65.12% of total healthcare expenditures in MS patients, with mean adjusted prescription costs being $13,092.16 higher than non-MS patients. Annual price increases for most DMTs have commonly exceeded 10% over the last 15 years.

A 2015 US study found MS prevalence was 572,312 with annual direct costs $24,327 higher for MS patients compared to non-MS individuals. MS patients had 3.3-fold higher odds of unemployment and lost an average of 10.04 QALYs compared to the non-MS cohort.

A 2022 study using Medicare claims data showed that for the 82% of individuals without subsidies, annual median total DMT costs were $56,794 with median out-of-pocket DMT costs of $4,566. Additionally, 93% of MS patients received supportive care medications, with annual median total costs for these drugs at $15,134.

Europe

In Italy (2019), mean annual costs were estimated at €39,307 per patient, varying by severity: €29,676 for mild, €43,464 for moderate, and €53,454 for severe cases. Direct healthcare costs were the major component (€21,069), followed by indirect costs (€15,004). The overall cost of MS in Italy was €4.8 billion, with the National Healthcare System sustaining most costs (80%).

A more recent 2024 Italian cross-sectional study estimated the mean total cost per MS patient at €20,299.4 per year, with costs increasing by disability level from €16,812.0 (minor) to €44,404.0 (severe). DMT costs accounted for 62.5% of total costs, while productivity loss accounted for 22.0%.

In Slovakia (2020), the total economic burden was €57,347,523, with total annual cost per patient of €6,682.

The International Multiple Sclerosis Study involving 19 countries reported average annual costs per patient to be €41,212, with direct medical costs of €21,093, direct non-medical costs of €2,110, and indirect costs of €16,318.

A 2021 Swedish study found mean annual excess costs of €7,381 for healthcare and €13,173 for productivity losses per person with MS. DMTs were the largest healthcare cost component at €4,262 per person, while productivity losses were predominantly from disability pension (79.3%).

General Trends

Costs are significantly higher for patients with severe disability compared to those with mild disability. Patients with relapses incur significantly higher costs compared to those without relapses. Pharmacy costs are the major cost drivers across all disability levels. Approximately 40% of working-age MS patients are not working due to MS, and costs rise steeply with increasing disability.