Nuvalent, a clinical-stage biopharmaceutical company, has announced the submission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for neladalkib, an investigational ALK-selective inhibitor for the treatment of patients with advanced ALK-positive non-small cell lung cancer (NSCLC) who have previously received tyrosine kinase inhibitor (TKI) therapy.

The NDA submission marks a significant milestone for the company, with neladalkib progressing from first clinical trial initiation to regulatory filing in under four years. The application is supported by data from the global ALKOVE-1 Phase I/II clinical trial, which evaluated the therapy in patients with advanced ALK-positive NSCLC who had been pre-treated with TKIs.

According to the company, neladalkib demonstrated encouraging anti-tumour activity in this patient population, including intracranial responses and the ability to address key mechanisms of disease progression. The therapy also showed a favourable safety profile, consistent with its design as a highly selective ALK inhibitor that spares the tropomyosin receptor kinase (TRK) pathway.

Neladalkib has received breakthrough therapy designation from the FDA for patients with locally advanced or metastatic ALK-positive NSCLC who have been treated with two or more prior ALK TKIs. It has also been granted orphan drug designation, reflecting its potential to address a rare and serious condition with limited treatment options.

The drug has been specifically designed to overcome resistance seen with earlier generations of ALK inhibitors, including tumours harbouring complex mutations such as G1202R. Its ability to penetrate the Central Nervous System (CNS) may also improve outcomes for patients with brain metastases, a common complication in advanced lung cancer.

The ALKOVE-1 trial, a first-in-human study, included a Phase I portion focused on safety, tolerability, dose determination and preliminary efficacy, followed by a Phase II portion designed with registrational intent. The study continues to enrol patients globally, including those with other ALK-positive solid tumours.

Nuvalent stated that detailed results from the trial will be presented at an upcoming medical conference. The company aims to work closely with the FDA during the review process to bring neladalkib to patients as quickly as possible.

With this submission, Nuvalent is advancing its strategy of developing precision therapies targeting clinically validated kinase pathways, addressing unmet needs in cancer treatment and improving outcomes for patients with resistant forms of the disease.