10 May 2019 - - The European Commission granted conditional marketing authorization for Lorviqua (lorlatinib, available in the US, Canada and Japan under the brand name Lobrena), as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase -positive advanced non-small cell lung cancer (NSCLC) whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor therapy, or crizotinib and at least one other ALK TKI, US-based pharmaceutical company Pfizer Inc. (NYSE: PFE) said.

Lorviqua is a third-generation ALK TKI that was specifically developed to penetrate the blood brain barrier, in the presence or absence of resistance mutations.

The conditional marketing authorization was based on results from a non-randomized, dose-ranging and activity-estimating, multi-cohort, multi-center Phase 1/2 study, B7461001, evaluating Lorviqua for the treatment of patients with ALK-positive advanced NSCLC, who were previously treated with one or more ALK TKIs.

A total of 139 patients with ALK-positive metastatic NSCLC after treatment with at least one second-generation ALK TKI, such as alectinib, brigatinib or ceritinib, were enrolled in the Phase 2 portion of the study.

Among these patients, the overall response rate for those who have been treated with one prior ALK TKI was 42.9% (95% CI: 24.5, 62.8) and 39.6% (95% CI: 30.5, 49.4) for those with two or more prior ALK TKI treatments (N=111).

In the trial, 67% of patients had a history of brain metastases.

Among 295 ALK-positive or ROS1-positive metastatic NSCLC patients who received Lorviqua 100 mg once daily in study B7461001, the most common (≥ 20%) adverse reactions were hypercholesterolemia (84.4%), hypertriglyceridemia (67.1%), edema (54.6%), peripheral neuropathy (47.8%), cognitive effects (28.8%), fatigue (28.1%), weight increased (26.4%), arthralgia (24.7%), mood effects (22.7%) and diarrhea (22.7%).

Conditional approval is granted to a medicinal product that fulfils an unmet medical need, where the benefit-risk balance is positive and the benefit of the product's immediate availability outweighs the risk of less comprehensive data than normally required.

Under the provisions of the conditional approval, Pfizer will provide additional data from the post-marketing studies, including the Phase 3 CROWN study of Lorviqua versus crizotinib in the first-line treatment of patients with ALK-positive NSCLC, which is currently ongoing.

Lorviqua is a TKI that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. Lorviqua was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier.