Abbvie, Roche’s Venclexta Endangers AML Approval With Flopped Confirmatory Trial

AbbVie and Roche notched a big win for blood cancer therapy Venclexta with a late 2018 FDA approval in the ultra-competitive acute myeloid leukemia (AML) market. But with only an early-stage trial to its name, Venclexta’s approval was conditional––and a failed confirmatory trial could now jeopardize its green light.

A combo of Venclexta and low-dose chemotherapy cytarabine (LDAC) failed to significantly extend AML patients’ lives over LDAC alone in a phase 3 trial meant to confirm Venclexta’s approval, AbbVie said Friday.

The Venclexta-LDAC combo posted a 25% reduction in the risk of death over solo LDAC and extended patients’ lives by a median 7.2 months compared with 4.1 months in the LDAC arm, AbbVie said.

The company has submitted data from the phase 3 Viale-C study to the FDA and global regulators, it said, with Neil Gallagher, AbbVie’s Chief Medical Officer and VP of development, adding in a statement that the results, “while not statistically significant, are indicative of the clinical activity” of the pairing.

In November 2018, the FDA approved Venclexta as a combination therapy with any of three chemo options to treat newly diagnosed patients aged 75 or older or those who aren’t eligible for intensive induction chemo.

As part of the accelerated approval, AbbVie agreed to to conduct confirmatory trials for Venclexta as an add-on to each of the three chemotherapies options, with the LDAC study reaching a readout first. The FDA based its approval on a phase 1/2 study showing 37% of trial patients hit remission on Venclexta with azacitidine, 54% on a Venclexta-decitabine regimen and 21% on Venclexta plus LDAC.

AbbVie said it had “several studies” in the AML confirmatory program underway, including Viale-A, a phase 3 trial examining a combo of Venclexta and azacitidine.

Still, the newest failure could dent AbbVie and Roche’s attempts to bring Venclexta outside of the profitable chronic lymphocytic leukemia (CLL)  market where it’s made its name. Since its first FDA nod in CLL back in 2016, Venclexta’s label has been expanded to include all relapsed CLL patients, rather than just those bearing a genetic mutation known as the 17p deletion.

That success led analysts to predict that Venclexta could hit $3 billion by 2022, putting it among oncology’s best-sellers in that year.

Even if Venclexta keeps its AML nod, it will face an tough battle with a number of competitors flooding into the market.

In November 2018––the same month as Venclexta’s conditional AML approval––Astellas’ Xospata notched an FDA approval for AML patients with one of two forms of FLT3 mutation who’ve relapsed or are resistant to standard chemotherapy. The same month, Pfizer’s Daurismo received its own AML nod, grabbing a win as a combo treatment with LDAC.

Another med in the market, Novartis’ Rydapt, received an FDA green light in 2017 specifically for newly diagnosed AML patients with a specific genetic mutation.-Fierce Pharma