Following in the footsteps of several Big Pharma companies, another ALK inhibitor has made its entry into the U.S. 

The new entrant is ensartinib from Xcovery Holdings, a subsidiary of China’s Betta Pharmaceuticals. The FDA on Wednesday approved the drug under the brand name Ensacove as a first-line treatment for ALK-positive non-small cell lung cancer among patients who’ve not previously received an ALK inhibitor.

Before the FDA go-ahead, ensartinib was first approved in China in 2020 under the trade name Beimeina. There, the drug moved into the first-line setting in 2022.

Betta noted that Ensacove marks the first innovative targeted lung cancer drug developed by a Chinese company to make it to the global market. Still, the drug is entering a niche market dominated by Big Pharma companies.

As a second-generation ALK inhibitor, Ensacove is clearly better than Pfizer’s first-generation Xalkori. But Roche’s Alecensa, Takeda’s Alunbrig and Pfizer’s third-generation med Lorbrena have all outperformed Xalkori to secure their respective first-line approvals from the FDA. Novartis also has an ALK inhibitor, Zykadia, which was cleared for first-line treatment in 2017 based on a comparison with chemotherapy.

The FDA’s nod for Ensacove came more than three years after results from the drug’s first-line eXalt3 study were published in JAMA Oncology. Compared with Xalkori, Ensacove reduced the risk of progression or death by 44% in first-line ALK-positive NSCLC, according to the FDA. No statistically significant difference in overall survival was observed, as Ensacove was linked to a non-statistically significant 12% lower risk of death.

The data cited by the FDA, which will be featured on Ensacove’s U.S. label, appear to come from a longer follow-up of eXalt3.

Ensacove’s efficacy data were not very differentiated compared with those Big Pharma offerings that have been available on the U.S. market for years.

The current ALK leader, Roche’s Alecensa, broke into the first-line ALK setting seven years ago after the phase 3 ALEX trial showed it slashed the risk of disease worsening or death by 47% versus Xalkori. The number later expanded to 57% at the trial’s final progression-free survival analysis. By that time, overall survival data were also immature but showed a 33% improvement trend in favor of the Roche med.

What’s more, Alecensa in April jumped into early-stage disease with a first-in-class FDA nod to treat ALK-positive NSCLC as an adjuvant treatment following tumor resection.

Ensacove has its own ongoing phase 3 in the adjuvant setting, albeit only among Chinese patients.

It’s estimated that about 5% of NSCLC cases are ALK-positive, and treatment can last for a long time for many patients. 

In the first nine months of 2024, Alecensa brought in 1.15 billion Swiss francs ($1.28 billion) in sales, while Pfizer’s Lorbrena commanded $538 million and Takeda’s Alunbrig generated 25.6 billion Japanese yen ($163 million). Still, those are large numbers compared with Betta’s 2.34 billion Chinese yuan ($321 million) of total revenue earned during the same period from five products, including ensartinib in China.

Betta Pharma is revered as a pioneer in China’s biotech industry. The company’s EGFR tyrosine kinase inhibitor icotinib, a competitor to AstraZeneca’s Tagrisso, was the first targeted cancer drug invented and fully owned by a Chinese company. Its approval by Chinese authorities in 2011 was hailed as a landmark event.

But the company has fallen behind many of its peers because of its heavy reliance on traditional small-molecule drugs rather than newer technologies.