Bayer pulls Aliqopa from US for follicular lymphoma

Bayer pulls Aliqopa from US for follicular lymphoma

Bayer has said it plans to withdraw its PI3K inhibitor Aliqopa from the US market as a treatment for follicular lymphoma (FL) after the drug failed a confirmatory trial, dealing another blow to the embattled drug class.

Aliqopa (copanlisib) was given accelerated approval by the FDA in 2017 as a third-line treatment for adults with relapsed FL, a form of non-Hodgkin lymphoma (NHL), based on response rate data from the phase 2 CHRONOS-1 study.

The CHRONOS-4 trial intended to show that the drug extended progression-free survival (PFS) when added to stand chemotherapy for patients with relapsed FL and other forms of NHL, including marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia after at least one prior line of systemic therapy, but missed the mark.

Now, Bayer says it is working with the FDA on withdrawing the drug while “exploring access options for patients currently receiving Aliqopa who have experienced a favourable response to treatment”, where their doctors feel it is warranted and no alternative drugs are available. It will publish the full results of CHRONOS-4 at a later date.

The withdrawal of Aliqopa is another example of the difficulties developers of PI3K inhibitors have encountered trying to prove that the drugs are effective in haematological cancers.

When it was approved, Aliqopa was positioned as a rival to Gilead Sciences’ Zydelig (idelalisib), also used as a third-line therapy for FL. Zydelig failed a confirmatory trial in that indication, however, and was withdrawn from sale last year, although it remains on the market as a treatment for chronic lymphocytic leukaemia (CLL).

Another drug that fell to the confirmatory trial curse was Secura Bio’s Copiktra (duvelisib), withdrawn for FL in 2021 but still available for CLL and small lymphocytic leukaemia (SLL).

MEI Pharma and partner Kyowa Kirin had to abandon plans to file for approval of their PI3K inhibitor zandelisib in B-cell lymphoma after being “discouraged” by the FDA from making the attempt based on a phase 2 study, and Incyte withdrew an application parsaclisib for FL, MZL and mantle cell lymphoma (MCL) after discussions with the FDA about its phase 2 data.

Meanwhile, Bayer also withdrew marketing applications filed in the US, EU and other markets in 2021 for Aliqopa as a therapy for various forms of NHL in combination with rituximab. Sales of the drug have never grown sufficiently to warrant being broken out in Bayer’s financial reporting.

Safety has long been an issue with the class, particularly infections, liver toxicity, diarrhoea and other gastrointestinal problems, and pneumonitis. For that reason, they have tended to be reserved for use after more tolerable agents.