Padcev–Keytruda combo receives orphan drug designation for bladder cancer

Approved by the FDA in November last year… gains momentum for its marketing authorization in Korea

Nirogacestat and tovorafenib also receive orphan drug designations.

The Padcev–Keytruda combination therapy for bladder cancer has been designated as an orphan drug in Korea. Since orphan drug designation enables expedited review by the Ministry of Food and Drug Safety (MFDS), the timeline to commercial approval is expected to be shortened.

On the 4th, the MFDS announced that it has designated three drugs, including the enfortumab vedotin–pembrolizumab combination therapy for bladder cancer, as orphan drugs.

Enfortumab vedotin is the generic name of Padcev, an antibody-drug conjugate (ADC) developed by Astellas. Pembrolizumab is the generic name of Keytruda, the immuno-oncology drug developed by MSD.

The newly designated orphan indication is muscle-invasive bladder cancer in the perioperative setting for patients ineligible for cisplatin-containing chemotherapy (limited to cases where both components are administered in combination).

This indication was approved by the U.S. FDA in November last year. Results from the KEYNOTE-905 clinical trial, which evaluated the combination therapy of the two drugs for bladder cancer, showed that the combination of Padcev and Keytruda improved event-free survival (EFS) by 60% compared to the control group (NR. vs 15.7 months; HR 0.40; 95% CI 0.28–0.57; P<.001), and overall survival (OS) improved by 50%. The pathological complete response rate (pCR) was also significantly higher in the Padcev-Keytruda combination group.

It appears that the company applied for domestic approval following FDA approval. If the combination therapy receives commercial approval, patient access to treatment is expected to improve substantially.

The orphan drug designation also includes nirogacestat (tablet) and tovorafenib (oral formulation).

Nirogacestat is a drug indicated for the treatment of desmoid tumors, marketed under the brand name Ogsiveo by Merck.

SpringWorks Therapeutics, a healthcare affiliate of Merck, received approval for the oral gamma-secretase inhibitor Ogsiveo from the European Commission (EC) in August last year as monotherapy for adults with progressing desmoid tumors requiring systemic treatment.

Ogsiveo is the first and only therapy approved in the European Union for the treatment of desmoid tumors.

Tovorafenib is a treatment for pediatric low-grade glioma (pLGG). It is a type II BRAF inhibitor developed for pediatric low-grade glioma patients with BRAF gene mutations. Marketed as Ipsen's ‘Ojemda,’ the drug received U.S. FDA approval in 2024. It is expected to provide a new treatment option for pediatric brain tumor patients who have failed existing therapies.

Designation as an orphan drug shortens the approval period through expedited review. Beyond conditional approval and fee reductions, submission requirements are simplified, including exemptions from bridging studies, and a fast-track approval process is conducted through priority review.