FDA nod for AZ’s Calquence sets up new Imbruvica showdown

AbbVie and Johnson & Johnson are facing a challenge to their blockbuster chronic lymphocytic leukaemia drug Imbruvica from AstraZeneca, after the FDA approved rival drug Calquence.

The US regulator has cleared BTK inhibitor Calquence (acalabrutinib) for previously-untreated and refractory CLL and small lymphocytic lymphoma (SLL), greatly expanding the eligible patient population for the drug beyond its current use in mantle cell lymphoma (MCL).

The approval prepares the ground for a second marketing tussle with Imbruvica (ibrutinib), the top-selling drug in the class with sales of $4 billion last year across multiple blood cancer indications, including CLL, SLL and MCL, in the US alone.

AZ also picked up simultaneous approvals in Canada and Australia under a new scheme called Project Orbis that allows filings to be made simultaneously to the FDA and other regulatory agencies.

Extending the use of Calquence into first-line CLL is seen as the key to unlocking the drug’s sales potential as AZ tries to continue the big progress it has made in oncology with its trinity of lung cancer therapy Tagrisso (osimertinib), ovarian and breast cancer drug Lynparza (olaparib) and immunotherapy Imfinzi (durvalumab).

Sales of Calquence in MCL have been relatively modest at $108 million in the first nine months of 2019 – with $44 million of that total coming from the third quarter – but AZ believes the CLL indication could help transform its fortunes.

The drugmaker quoted potential peak sales of around $5 billion when it acquired the molecule in 2015 along with a majority stake in Acerta Pharma for $4 billion.

Many analyst forecasts are considerably lower on the grounds that Calquence will not find it an easy task displacing Imbruvica, which is expected to peak at around $7 billion in annual sales.

Both Imbruvica and Calquence are also facing competition from BeiGene’s BTK inhibitor Brukinsa (zanubrutinib), newly-approved by the FDA for MCL and also in late-stage development for other blood cancer indications including CLL, SLL, follicular lymphoma (FL) and marginal zone lymphoma (MZL).

Calquence’s approval in CLL comes on the strength of the ASCEND and ELEVATE-TN trials, which were both halted early and showed that the drug improved progression-free survival in refractory and previously-untreated CLL, respectively.

Both AZ and BeiGene are hoping to dislodge Imbruvica by running head-to-head trials of their new drugs against the market leader, focusing on second-line treatment of previously-treated CLL.

AZ is sponsoring the ACP-196 trial of Calquence and Imbruvica while BeiGene is pitting Brukinsa against AbbVie/J&J’s drug in the ALPINE study, due to complete in 2020 and 2021, respectively.