Rallybio Drops Maternal Disorder Drug Following Phase 2 Failure

US-based biotechnology company Rallybio is discontinuing its RLYB212 program for preventing the development of fetal and neonatal alloimmune thrombocytopenia (FNAIT) due to unsatisfactory outcomes from a Phase II study.

FNAIT is an uncommon, pregnancy-associated illness in which a mother’s immune system targets the infant’s platelets, resulting in thrombocytopenia and possibly severe hemorrhagic outcomes.

The firm’s primary asset, RLYB212, did not provide required effectiveness signals or pharmacokinetic data, nor did it reach anticipated target concentrations in a Phase II study, ultimately leading to its demise.

Rallybio CEO Dr Stephen Uden expressed disappointment regarding the pharmacokinetic outcomes observed in the Phase II trial of RLYB212. He noted that the findings differed substantially from expected projections, and without empirical data to guide further dose modifications, the risk-to-benefit ratio no longer justifies continuing the treatment.

The single-arm Phase II study aimed to evaluate the pharmacokinetics as well as safety of RLYB212, a subcutaneous human monoclonal anti-HPA-1a antibody, in women undergoing pregnancy who are at an elevated risk for HPA-1a alloimmunization and FNAIT. The secondary endpoints included the evaluation of pregnancy and neonatal/infant outcomes, as well as the incidence of emergent HPA-1a alloimmunization.

Second-trimester pharmacokinetic findings from patients indicated that RLYB212 failed to reach the anticipated goal concentrations of 6 ng/mL to 10 ng/mL, as well as the minimal effectiveness threshold of 3 ng/mL. The research also concluded that dosage modification is impractical. Rallybio suggests that the expression of the HPA-1a antigen on the placenta may influence plasma levels of RLYB212.

Enrollment in the study has been terminated, and all participant screening has ceased. The monitoring of patient safety will go on as outlined in the clinical study guidelines.

Rallybio has an additional drug, RLYB116, a C5 inhibitor for use in the management of complement-mediated disorders, including myasthenia gravis (MG), which it will now prioritize in clinical development. RLYB116 is undergoing a Phase 1 study to assess the treatment in healthy volunteers. In September 2023, the first results from the study were revealed, indicating RLYB-116’s potential efficacy.

Should it get approval, GlobalData forecasts that RLYB-116 sales would reach $1.23 billion by 2030.

Dr Uden emphasized that Rallybio remains fully committed to its mission of developing groundbreaking treatments. He stated that the company is dedicated to delivering value to shareholders by progressing a pipeline of potentially leading therapies for individuals with rare conditions. This includes the aforementioned RLYB116, REV102—an ENPP1 inhibitor aimed at treating hypophosphatasia—and RLYB332, a long-acting antibody targeting matriptase-2 for addressing iron overload disorders.