The European Medicines Agency (EMA) has granted marketing authorization for Ogsiveo (nirogacestat), a gamma-secretase inhibitor from SpringWorks Therapeutics, for the treatment of adult patients with progressive desmoid tumors requiring systemic therapy. Desmoid tumors are locally aggressive and can cause significant morbidity and pain, but until now, there have been no approved targeted therapies, and treatment has relied on off-label use of chemotherapy or surgery. This approval marks a significant milestone, as Ogsiveo is the first and only targeted therapy approved in the European Union for desmoid tumors. It is expected to transform the treatment paradigm for this rare disease by addressing the limitations of existing non-targeted therapies, such as high recurrence rates and significant side effects.

The approval is based on the positive results from the global, randomized Phase 3 DeFi study (NCT03785964). In the study, Ogsiveo demonstrated a 71% reduction in the risk of disease progression or death compared to placebo, with a hazard ratio (HR) of 0.29 (p<0.001) for progression-free survival (PFS). The objective response rate (ORR) was also significantly higher in the Ogsiveo arm (41%) compared to the placebo arm (8%). In addition, Ogsiveo demonstrated consistent improvements in patient-reported outcomes, including pain reduction and quality of life (QoL).

Following FDA approval in November 2023, this EMA approval establishes Ogsiveo as a key asset in major global markets. With a global desmoid tumor market estimated at over $1 billion, Ogsiveo is positioned to capture a significant share as the first-in-class therapy. It also provides a significant lead over potential competitors, such as AL102 from Ayala Pharmaceuticals, with a potential three-year advantage. Furthermore, the potential for expanding the indications, such as in combination with a BCMA-targeted inhibitor for the treatment of multiple myeloma, is also being explored.

The commercial success of Ogsiveo will depend on securing reimbursement in European countries. The pricing and reimbursement decisions in key markets, such as Germany, France, and Italy, will be critical in determining the initial sales trajectory. While Ogsiveo has been granted orphan drug designation, which provides 10 years of market exclusivity in Europe, the pricing and reimbursement decisions will need to take into account the budgetary constraints of national healthcare systems. If negotiations with national authorities are successful, Ogsiveo is expected to rapidly capture a significant share of the 1,300 to 2,300 new desmoid tumor patients diagnosed annually in Europe.