Summary of PTC Therapeutics (PTCT) Update / Briefing May 17, 2023 Company Overview - **Company**: PTC Therapeutics (PTCT) - **Product**: Sepiaterin - **Indication**: Treatment of Phenylketonuria (PKU) Key Points Industry and Product Development - **Phase III Trial**: The AFFINITY trial for sepiaterin in patients with fetal ketonuria has shown positive top-line results, meeting the primary endpoint of blood phenylalanine reduction [2][19] - **Efficacy Results**: - Overall mean blood phenylalanine reduction of **63%** in the primary analysis population [2][8] - In classical PKU patients, the mean reduction was **69%** [2][8] - **84%** of patients achieved the target phenylalanine level of less than **360 micromoles per liter** [10] - **93%** of adolescents and adults met the European guideline target of below **600 micromoles per liter** [10] Trial Design and Results - **Trial Structure**: The trial included a run-in phase where patients were treated with sepiaterin for two weeks before randomization [3][4] - **Patient Population**: - Total of **156 patients** screened, with **103 patients** showing a reduction of greater than **30%** in blood phenylalanine levels [4][6] - **98 patients** were randomized for the primary analysis [6] - **Safety Profile**: - No serious adverse events reported; common adverse events included headache and diarrhea, mostly grade one [12][13][78] - Similar rates of treatment-related adverse events between sepiaterin and placebo groups [13][78] Market Opportunity - **Commercial Potential**: - PKU represents a unique commercial opportunity with an estimated **58,000 patients** worldwide [17] - Despite two approved therapies, a large unmet need exists, particularly for therapy-naive patients and those poorly controlled on existing treatments [17][18] - **Regulatory Strategy**: Plans to request pre-submission meetings with regulatory authorities and move forward with NDA and MAA submissions [19] Competitive Landscape - **Comparison with Kuvan**: - In a subset of patients previously treated with Kuvan, sepiaterin showed a **48%** reduction in blood phenylalanine levels compared to their baseline on Kuvan [11][25] - The trial results validate the superior efficacy of sepiaterin over Kuvan, with a higher percentage of patients achieving significant benefits [25][26] Future Directions - **Long-term Studies**: Ongoing long-term open-label studies to assess safety and durability of sepiaterin treatment [14][19] - **Phe Tolerance Protocol**: Preliminary data show that patients can tolerate increased phenylalanine intake while maintaining low blood levels [16][104] Conclusion - The AFFINITY trial results position sepiaterin as a promising treatment for PKU, with strong efficacy and safety data supporting its potential to address significant unmet medical needs in the PKU patient population [19][121]