BioMarin reported that its enzyme replacement therapy for ENPP1 deficiency failed to show clinical benefit in a phase 3 study, delivering a setback for the company’s rare disease pipeline. The program, targeting patients who lack sufficient ENPP1 activity, produced mixed results in late-stage evaluation, according to the report. The outcome is likely to narrow the probability of regulatory success and may prompt reassessment of next development steps or post-trial analysis plans. BioMarin’s ENPP1 effort had been positioned as a potentially transformative approach in a patient population with limited therapeutic options. The failure adds to the scrutiny regulators and investors apply to rare disease approvals, especially where endpoints and magnitude of benefit become decisive.