FDA designates Nuvalent's NVL-655 as breakthrough therapy

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation (BTD) to Nuvalent’s NVL-655, a brain-penetrant anaplastic lymphoma kinase (ALK)-selective tyrosine kinase inhibitor (TKI), for the treatment of non-small cell lung cancer (NSCLC). This designation is specifically aimed at patients who have locally advanced or metastatic ALK-positive NSCLC and have previously undergone treatment with two or more ALK TKIs.

NVL-655 is designed to tackle several clinical challenges, including emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events. These issues often arise due to the structurally related tropomyosin receptor kinase (TRK) family, which can complicate treatment outcomes.

The FDA's decision to grant BTD for NVL-655 is based on initial efficacy and safety data obtained from the Phase I segment of the Phase I/II ALKOVE-1 clinical trial. Currently, the Phase II portion of the ALKOVE-1 trial is enrolling participants, and Nuvalent plans to present updated data in the second half of this year.

Breakthrough therapy designation is intended to expedite the development and review process for drugs that treat serious conditions and where preliminary evidence indicates that the drug may significantly improve upon existing therapies. Under this designation, the FDA provides intensive guidance and may allow for a rolling review process to speed up the drug's assessment.

NVL-655 has also previously been awarded orphan drug designation for the treatment of ALK-positive NSCLC. According to Nuvalent's chief development officer, Darlene Noci, the breakthrough therapy designation for NVL-655 is a significant milestone for their ALK program. It is also the second breakthrough designation granted to their pipeline of novel kinase inhibitors this year. The company is committed to advancing NVL-655 rapidly, recognizing the ongoing need for innovation in treating patients with ALK-positive NSCLC who have exhausted available therapies. Nuvalent expects to provide an update from the ALKOVE-1 trial of NVL-655 at a medical meeting in the latter half of this year.