Takeda sets sights on first-line lung cancer market with new Alunbrig data

Pfizer’s ALK inhibitor Xalkori is facing a further challenge from Takeda newcomer Alunbrig, which outperformed it in a phase 3 trial.

Takeda has reported updated results from its ALTA-1L trial of Alunbrig (brigatinib) versus Xalkori (crizotinib) in first-line treatment of AK-positive non-small cell lung cancer (NSCLC), saying that its drug was better at reducing the risk of disease progression or death over more than two years of follow-up.

Median progression-free survival was three times as long with Alunbrig as with Xalkori – at 29.4 months versus 9.2 months. Meanwhile, Takeda’s drug reduced the risk of disease progression or death by 57% in the overall population, and 69% in patients whose cancer had spread to the brain.

The presentation of earlier data from the trial a year ago fired a shot over Pfizer’s bows, and now Takeda says it intends to file for approval of Alunbrig as a first-line treatment for patients with ALK-positive NSCLC.

Alunbrig is one of a series of new ALK inhibitors that are deemed to be more potent than Xalkori, penetrate into the brain more readily and have activity against the most common crizotinib resistance mutations.

Alunbrig is already approved for use in patients who have progressed despite first-line ALK inhibitor treatment, but extending into first-line use will allow Takeda to mount a direct challenge against Xalkori and other second-generation drugs in the class, such as Roche’s Alecensa (alectinib) and Novartis’ Zykadia (ceritinib) – which both also bested Xalkori in first-line trials.

Sales of Xalkori have been on the slide since Zykadia and Alecensa claimed approval for use in previously-untreated patients two years ago. Pfizer made $385 million worldwide from the drug in the first nine months of 2019, having peaked at just under $600m in 2017.

Alecensa is in the ascendency at the moment, growing 50% to CHF 656 million ($657 million) in the first three quarters of this year, while Zykadia is clearly trailing its rivals as it doesn’t warrant having its sales broken out in Novartis’ quarterly results statements.

Takeda said at the end of October that Alunbrig made 3.4 billion yen (around $31 million) in the first six months of its current financial year from second-line use.

It reckons however that the impressive efficacy seen in ALTA-1L, as well as a good safety profile, give it a chance of competing against its three rivals in first-line ALK-positive NSCLC and could kickstart sales growth.

Pfizer isn’t about to cede control of the ALK inhibitor market without a fight however, and at the end of 2018 it claimed US approval for Lorbrena (lorlatinib), its own second-generation drug, as a second-line option for lung cancer.

The company is conducting its own head-to-head trial of Lorbrena and Xalkori in previously-untreated patients with results due early next year, according to the clinicaltrials.gov database.