Breakthrough Clinical Results
IDEAYA Biosciences announced positive Phase 2 clinical data for darovasertib in the neoadjuvant setting of primary uveal melanoma (UM). The OptimUM-09 trial demonstrated significant ocular tumor shrinkage, high eye preservation rates, and reduced predicted radiation dose to the eye. A notable percentage of patients also experienced improved visual acuity. Darovasertib has received U.S. FDA Breakthrough Therapy Designation in the neoadjuvant setting for enucleation-eligible patients. IDEAYA is also conducting a Phase 3 trial (OptimUM-10) of darovasertib as a single-agent in the neoadjuvant setting of primary UM.
Key Highlights
- 83% of patients demonstrated ocular tumor shrinkage with darovasertib treatment.
- 57% eye preservation rate in enucleation-recommended patients, increasing to 95% in patients achieving ≥20% tumor shrinkage.
- 70% of plaque brachytherapy-eligible patients achieved a reduction in predicted radiation dose to the eye.
- Darovasertib was generally well tolerated with manageable adverse events.
Incidence and Prevalence
Global Uveal Melanoma Incidence and Prevalence
Global Incidence Rates
Uveal melanoma is the most common primary ocular malignancy among adults, representing only 4% of all melanomas with a general incidence rate of 0.6 per 100,000. Incidence rates vary significantly by region:
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North America:
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United States: 5.1-5.2 per million (1973-2013)
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Canada: 3.34 per million (1992-2010) increasing to 5.09 per million (2011-2017)
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Meta-analysis estimate: 5.74 per million (95% CI: 4.37-7.11)
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Europe:
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Overall: 3.1 to 5.8 per million (1995-2002)
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Sweden: 5.6 per million (1960-2009)
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Germany: 6.41 per million (2009-2015)
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Poland: 6.67 per million (2010-2017)
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United Kingdom: 10 per million (1999-2010)
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Hungary: 6.40-10.96 per million person-years (2012-2021)
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Meta-analysis estimate: 7.30 per million (95% CI: 6.36-8.24)
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Oceania:
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New Zealand: 5.56 per million (2000-2020)
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Australia: 7.6 per million (1982-2014)
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Asia:
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South Korea: 0.60 per million (1999-2011)
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Uveal melanoma specifically: 0.42 per million (1999-2011)
Geographic and Demographic Patterns
- Latitude correlation: Incidence correlates with latitude (r = 0.77), with a north-to-south decreasing gradient in Europe
- Genetic factors: Incidence correlates with SNP rs12913832 (r = 0.83), blue iris color (r = 0.56), green iris color (r = 0.51), and negatively with brown iris color (r = -0.64)
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Racial distribution:
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98% of cases affect Caucasians
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In the US, relative risk compared to Black patients: 19.2 for non-Hispanic whites, 5.4 for Hispanic patients, and 1.2 for Asian and Pacific Islander patients
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The overall white:black ratio is 18:1
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Gender differences: Incidence is slightly higher in males than females
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In the US: males 4.9 per million vs females 3.7 per million
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In Hungary: highest rate among men at 13.38 per million person-years (2015)
Trends
- North America: A significant decreasing trend according to meta-analysis
- Europe: No significant trend detected in meta-analysis
- Canada: Ongoing, steady increase with rates doubling between 1992-2010 and 2011-2017
- South Korea: Higher rates in 2006-2011 than in 1999-2005
- Most countries (28/35) show stable incidence trends
Prevalence and Mortality
Uveal melanoma is considered a rare disease, but has high mortality: * 90% of affected patients die within 15 years * Swedish 5-year survival: 60.3% (crude) and 70.1% (relative) * Finnish long-term mortality: 31% by 5 years, 45% by 15 years, 49% by 25 years, and 52% by 35 years * Metastatic uveal melanoma is the leading single cause of death throughout follow-up
Key Unmet Needs and Target Populations in Uveal Melanoma
Diagnostic and Prognostic Challenges
- Gene expression profiling (GEP) has significant limitations with a substantial probability of misclassification (11.3-16.3%)
- Two-site sampling is recommended to reduce the risk of underestimating metastatic risk
- Tissue biopsy is not routinely recommended due to risk of extraocular dissemination
- Patients with different gene expression profiles are being studied, particularly those with class 1b tumors where 50% showed low nuclear BAP1 expression
Treatment Challenges
- Metastatic uveal melanoma (mUM) currently has no curative treatment available
- Unlike cutaneous melanoma, there are no established treatments that significantly improve outcomes
- Immunotherapy approaches effective in cutaneous melanoma show little or no success in uveal melanoma
- Tebentafusp is the only FDA approved immunotherapy for metastatic uveal melanoma in HLA-A02:01 positive patients
- Patients with ICI-resistant/ICI-refractory disease, CNS metastases, history of autoimmune disease, and those with immune-related adverse events lack evidence-based treatment guidance
High-Risk Populations Being Targeted
- Patients with high risk of developing metastases are being targeted through BAP1 expression assessment
- Patients with low nuclear BAP1 expression (68% developed metastasis vs. 9% with high expression)
- Patients requiring monitoring for metastasis development using circulating tumor DNA (ctDNA) as a biomarker
- Patients with specific genetic markers (HTR2B, EEF1A2, FEZ1, GRID1, HAP1, and SPHK1) associated with poorer prognosis
- Patients with metastatic potential evaluated using prognostic models based on S100A4, PDE4B, CHCHD10, NSG1, and C4orf48 genes
Research Needs
- Large-scale translational research programs based on stored human samples
- Identification of new biomarkers for early diagnosis and new targeted treatment modalities
- More research on the biology of uveal melanoma and improvements upon current technologies
- Better understanding of the molecular basis of local myelomonocytic cell population
- Development of efficacious, safe, and noninvasive therapeutic approaches
- Novel treatment approaches including transarterial chemoembolization, melphalan percutaneous hepatic perfusion, and targeted therapies based on GNAQ and GNA11 mutations
Patient Support Needs
- Decision-making about cytogenetic testing (CGT) for prognostication is burdensome to many patients
- Patients need careful support by psycho-oncologists considering their fears and expectations
- Patients reject CGT when they worry that knowing results will have an unintended influence on their life
Company drugs in pipeline
IDEAYA Biosciences Drug Pipeline Indications
I don't have specific information about IDEAYA Biosciences' drug pipeline indications. The available data doesn't contain details about which cancer types or medical conditions IDEAYA is developing treatments for, nor does it provide information about their current drug development programs.
For accurate and up-to-date information about IDEAYA Biosciences' pipeline, it would be advisable to:
- Visit the company's official website
- Review their recent investor presentations
- Check their SEC filings
- Examine recent press releases
- Consult clinical trial registries like ClinicalTrials.gov
IDEAYA Biosciences is a precision medicine company that typically focuses on targeted therapeutics for specific patient populations based on molecular profiling. Their approach likely involves developing drugs that target specific genetic mutations or molecular pathways involved in various diseases, particularly in oncology.
The field of precision oncology has been advancing rapidly, with companies like IDEAYA working on treatments that address specific biomarkers and genetic alterations found in different cancer types. These targeted approaches aim to improve efficacy while reducing side effects compared to traditional treatments.
To understand IDEAYA's current focus areas, consulting their latest corporate communications would provide the most accurate picture of their clinical pipeline, including which indications they are prioritizing and what stage of development each program has reached.