Allarity, after some forced clarity from FDA, pivots lead asset hopes to combo approach

After a meeting with the FDA, Allarity Therapeutics is abandoning hope that its lead clinical asset could be sold as a monotherapy for a type of advanced kidney cancer, opting instead to restructure its entire pipeline around combination therapies.

The biotech obtained dovitinib—a small-molecule, pan-tyrosine kinase inhibitor—in 2018 from Swiss drug giant Novartis, centering its pipeline around the drug. Allarity hoped dovitinib would be approved for adults with metastatic renal cell carcinoma (mRCC) in 2022, even signing on to a manufacturing agreement with CDMO giant Lonza that would support potential commercialization.  

However, those dreams have spiraled down the drain as Allarity’s board of directors mandated the biotech move away from monotherapy development, according to an Aug. 2 release. The decision hinges on a recent advisory meeting with the FDA about dovitinib’s potential phase 3 clinical development for third-line mRCC patients.

In December, Allarity submitted a new drug application to the FDA for dovitinib for third-line treatment of mRCC. The application was based on results from GOLD, a phase 3 trial that compared dovitinib to Bayer’s Nexavar in these patients. Results show patients receiving dovitinib had a median survival rate of 15 months, compared with 11.2 months for those treated with Nexavar. 

In February, the FDA responded to Allarity’s application with a refusal to file letter, which means the agency won’t review the application because significant deficiencies were identified.  

Allarity recently met with the agency regarding the application and refusal to file letter. The FDA said under its Project Optimus guidelines—a new initiative launched in May meant to optimize therapeutic dosing in oncology—Allarity would likely need to conduct a new dosing study for dovitinib before launching any future phase 3 trials that would allow for the submission of another application.

A new dovitinib dosing study would further delay a future late-stage study and would increase cost, time and market risk for advancing the drug alone in an increasingly competitive indication, according to the Allarity release. For these reasons, the biotech has decided that advancing dovitinib as a monotherapy in adults isn’t commercially viable or in the best interests of its shareholders. However, Allarity will continue to develop the drug in partnership with OncoHeroes Biosciences as a possible monotherapy for pediatric cancers.

Allarity’s board said refocusing the pipeline on combination therapies aligns with a current shift toward combination therapies in oncology standard-of-care.

As part of its new strategy, Allarity plans to start enrolling participants for a phase 1b/2 study of stenoparib, a PARP inhibitor, in combination with dovitinib for second-line or later treatment of metastatic ovarian cancer.   

The biotech’s cancer candidates are all built around its drug response predictor diagnostic tool, which is used to identify patients who have a high genetic likelihood of responding to certain drugs. Allarity will continue its current phase 2 trial assessing stenoparib as a monotherapy for ovarian cancer, with an interim data readout anticipated in the fourth quarter of this year.

The biotech also has Ixempra, an FDA-approved microtubule inhibitor used to treat second-line metastatic breast cancer.

The company is currently led by interim CEO James Cullem, who assumed the temporary role this June after Steve Carchedi stepped down to “pursue other opportunities,” according to a news release. The board anticipates naming a permanent CEO in the first quarter of next year.