China NMPA grants breakthrough therapy status to Hutchmed’s amdizalisib to treat r/r follicular lymphoma

Hong KongTuesday, September 14, 2021, 17:00 Hrs  [IST]

Hutchmed announces that the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) to amdizalisib (HMPL-689), a highly selective and potent PI3Kd inhibitor, for the treatment of relapsed or refractory (r/r) follicular lymphoma (FL), a subtype of non-Hodgkin’s lymphoma (NHL).

NMPA grants BTD to new drugs that treat life-threatening diseases or serious conditions for which there are no effective treatment options, and where clinical evidence demonstrates significant advantages over existing therapies. Drug candidates with BTD may be considered for conditional approval and priority review when submitting a New Drug Application (NDA). This indicates that the development and review of amdizalisib for relapsed or refractory FL may be expedited, to address patients' unmet needs more quickly.

Christian Hogg, CEO of Hutchmed, said, “The granting of BTD to amdizalisib by the NMPA underscores the promising clinical value of this highly selective and potent PI3Kd inhibitor. There is a clear need for new therapies in this treatment setting, particularly with regard to specific toxicities and suboptimal efficacy with existing treatments across different lymphoma subtypes. We look forward to important clinical data on amdizalisib being presented at the ESMO Congress next week and are continuing to accelerate global development of this novel therapy.”

Updated preliminary results from the ongoing phase Ib expansion study in China will be presented as a Proffered Paper at the 2021 ESMO (European Society for Medical Oncology) Congress on September 20, 2021. To date, amdizalisib has been shown to be well tolerated, exhibiting dose-proportional pharmacokinetics (PK), a manageable toxicity profile, and single-agent clinical activity in relapsed/refractory B-cell lymphoma patients.

Hutchmed has initiated an extensive, globally-focused clinical development pathway for amdizalisib. In April 2021, Hutchmed initiated a phase II registration study in China for amdizalisib in approximately 100 patients with relapsed or refractory FL and approximately 80 patients with marginal zone lymphoma (MZL). The trial is being conducted in over 35 sites in China.

PI3Kd (phosphoinositide 3-kinase delta) is a lipid kinase that controls the activation of several important signaling proteins. Upon an antigen binding to B-cell receptors, PI3Kd can be activated through the Lyn and Syk signaling cascade. The abnormal activation of B-cell receptor signaling is closely related to the development of B-cell type hematological cancers, which represent approximately 85% of all NHL cases. Therefore, PI3Kd is considered a promising target for drugs that aim to treat certain hematologic cancers.

Amdizalisib (HMPL-689) is a novel, selective and potent oral inhibitor targeting the isoform PI3Kd. Amdizalisib’s PK properties are favorable with good oral absorption, moderate tissue distribution and low clearance in preclinical PK studies, suggesting a low risk of drug accumulation and drug-to-drug interaction. Because of its high target selectivity and optimal PK profile, amdizalisib has the potential to demonstrate an optimal benefit-risk profile in this class.