Pfizer's Lorbrena breaks into front-line ALK lung cancer, jostling with Novartis, Roche and Takeda

Pfizer’s Lorbrena has finally broken into front-line non-small cell lung cancer, where Novartis, Roche and Takeda are already jockeying for a niche market.

The FDA expanded Lorbrena’s use into newly diagnosed patients with ALK-positive NSCLC, Pfizer said Wednesday. With that front-line nod, the agency converted Lorbrena's conditional green light for previously treated cases into a full approval.

How does Pfizer expect to compete in such a crowded field? As a third-generation ALK inhibitor, Lorbrena has arguably the best efficacy data in head-to-head tests against its predecessor, Xalkori.

In the phase 3 Crown trial, Lorbrena cut the risk of tumor progression or death by 72% over Xalkori. The number looks notably better than the Xalkori beats posted by second-generation ALK inhibitors.

Roche’s Alecensa cut that same risk by 50% in its phase 3 Alex trial, while Takeda’s Alunbrig performed similarly with a 51% reduction in its own phase 3 trial. Novartis’ Zykadia secured its front-line nod in 2017 with chemotherapy-topping data, rather than a Xalkori comparison, showing a 45% risk reduction in disease worsening or death compared with the older regimen.

RELATED: ESMO: Pfizer's Lorbrena blows Xalkori out of the water in bid for front-line, ALK-positive lung cancer use

As the first ALK inhibitor on the market, Pfizer’s Xalkori has one major shortcoming—it doesn’t work well against brain metastases; it doesn’t appear to penetrate the blood-brain barrier. An estimated 40% of people with ALK-positive metastatic NSCLC have brain metastases at diagnosis.

Pfizer designed Lorbrena with that shortfall in mind.

 In a subset of Crown participants with measurable brain metastases, Lorbrena shrunk tumors in 82%, way more than the 23% rate in the Xalkori arm. Lorbrena also significantly extended the time to central nervous system progression, slashing that risk by a whopping 93% over Xalkori.

But while Lorbrena has put up the best efficacy numbers, it remains to be seen whether doctors will indeed choose the third-gen med over its rivals for newly diagnosed patients—and safety could be an issue.

RELATED: ASCO: Roche's Alecensa stays on top of Xalkori with long-term survival showing

Probably because of its strong brain-penetrating ability, Lobrena has shown some unique side effects such as cognition and mood changes. Even though these problems were typically mild and reversible with dose interruption, they could factor into physicians’ prescribing decisions. It’s also possible that physicians might be inclined to reserve a drug with such high efficacy to later lines of therapy.

ALK pathology represents a niche market in NSCLC, accounting for roughly 3% to 5% of all cases.

Still, in 2020, Roche’s Alecensa brought in sales of CHF 1.16 billion ($1.26 billion), up 40% year over year at constant currencies. Takeda’s Alunbrig, which just nabbed its own first-line FDA nod last May, hauled in JPY 6.5 billion ($60.5 million) in the nine months ended in December despite a 29% year-over-year increase.

Lobrena’s new go-ahead was reviewed under Project Orbis, which allows for concurrent filings and collaborative review with other drug authorities in Canada, Singapore, Switzerland, Australia, Brazil and the U.K.

Editor's Note: This story has been corrected to show that Alunbrig's JPY 6.5 billion sales were for three quarters ended in December, not three months.