Breakthrough Clinical Results

Servier and IDEAYA Biosciences announced an exclusive license agreement for darovasertib, a PKC inhibitor, for uveal melanoma treatment outside the US. Servier will gain regulatory and commercial rights, paying IDEAYA $210 million upfront and up to $320 million in milestones, plus royalties. Darovasertib is in Phase 2/3 and Phase 3 trials for metastatic and primary uveal melanoma, respectively, with a goal to launch a global Phase 3 adjuvant trial in 2026. The drug has received FDA Breakthrough Therapy and Fast Track designations, and Orphan Drug status.

Incidence and Prevalence

Global Incidence and Prevalence of Uveal Melanoma

Uveal melanoma is the most common primary intraocular malignancy in adults, despite comprising less than 5% of all melanomas. This life-threatening disease shows significant geographic and demographic variations in its distribution worldwide.

Global Incidence Patterns

The global distribution of ocular melanoma follows a distinct pattern:

• High incidence regions (≥8.0 cases per million person-years): Northern Europe, Western Europe, and Oceania
• Moderate incidence regions (2.0 to 7.9 cases per million person-years): North America, Eastern Europe, and Southern Europe
• Low incidence regions (<2.0 cases per million person-years): South America, Asia, and Africa

Notably, ocular melanoma incidence strongly correlates with latitude (r = 0.77, P ≤ 0.001) and is expressed as a north-to-south decreasing gradient in Europe. This geographic pattern is partly explained by selection for lighter pigmentation in the past 5000 years, which accounts for approximately 73% of the difference in uveal melanoma incidence between Northern and Southern Europe.

Recent Incidence Data

In the United States, data from the Surveillance, Epidemiology, and End Results database between 1973 and 2012 reported a mean age-adjusted incidence of 5.1 per million (95% CI 4.2-6.1). The incidence is higher in males (5.9, CI =4.4-7.6) compared to females (4.5, CI =3.3-5.8), P<0.001.

A Canadian study documented that the 2011-2017 age-standardized incidence rate for uveal melanoma was 5.09 cases per million individuals per year (95% CI, 4.73-5.44), representing an increase from the 1992-2010 rate of 3.34 cases per million individuals per year. The incidence rate in Canada has doubled between these periods, from 0.074 to 0.15 cases per million individuals per year.

Demographic Patterns

Uveal melanoma most commonly occurs in the sixth decade of life (61.4±15 years) and among Caucasians (94.7%). The disease is rare in Asian countries like Malaysia, though there is an increasing number of cases reported. In a Malaysian study, eight cases of choroidal melanoma were identified with a median age of 65 years, with six females and two males.

The incidence is particularly low among blacks. A case report described a 38-year-old black man diagnosed with choroidal melanoma with extensive orbital invasion, which is highly unusual and represents the youngest reported case of choroidal melanoma with extrascleral extension in a black patient.

Survival and Mortality

About half of patients diagnosed with uveal melanoma will develop metastases within 10 to 30 years, most commonly in the liver. The median survival time after metastasis is 4-5 months, and once metastases develop, the 3-year survival rate drops rapidly to 13%.

The mean overall and cancer-specific 5-year relative survival rates were 79.8%±5.8% and 76%±5.3%, respectively. Despite changes in treatment approaches, the 5-year cancer-specific survival rate has remained relatively unchanged over time.

Drug used in other indications