Venetoclax approval could open doors for AbbVie


The speedy green light for AbbVie and Roche’s venetoclax might have come in a small population – patients with relapsed or refractory chronic lymphocytic leukemia with the highly aggressive 17p deletion – but it could act as a springboard for approval in other indications or as part of a combination therapy, where various trials are already under way (see table below).

There is not much doubt about the efficacy of venetoclax, a first-in-class Bcl-2 inhibitor now known as Venclexta. But questions might linger about its safety. If these can be allayed and the drug expanded into broader uses, sales could hit $1.8bn by 2020, according to EvaluatePharma’s consensus of sellside forecasts.

The phase II study on which Venclexta’s approval is based showed an impressive overall response rate of 80%, compared with a 58% ORR in a phase I/II trial of Abbvie/Johnson & Johnson's Imbruvica in relapsed/refractory CLL, although the usual caution about cross-trial comparisons applies.


Venclexta had once been billed as the biggest incoming threat to Imbruvica, but AbbVie’s acquisition of Imbruvica’s originator, Pharmacyclics, made the drugs stablemates, and a combination now seems the most likely outcome. Several studies of this combo are already recruiting patients, according to

Venclexta is also being combined with other drugs including Roche’s Rituxan and Gazyva. It was jointly developed by Roche and AbbVie in a deal that involves splitting US sales 50/50, and AbbVie paying undisclosed royalties to Roche on ex-US sales.

The drug has FDA breakthrough therapy designation in combination with Rituxan in relapsed/refractory CLL and in treatment-naive acute myeloid leukaemia patients unable to receive standard chemotherapy.

One thing to watch out for in future trials will be side-effects, particularly tumour lysis syndrome, which caused several deaths in early trials. AbbVie believes that it solved this problem with dosing adjustments, and no more deaths have been reported since the 2013 ASH meeting.

If the drug’s safety record remains intact and it proves its worth in bigger indications this will provide some consolation to AbbVie, which is facing falling sales of its blockbuster Humira as biosimilars come into play.

New drugs are therefore vital, and Venclexta will have its role to play. It could follow in the footsteps of Imbruvica, which recently got the go-ahead in first-line CLL after also starting off in relapsed/refractory patients with the 17p deletion. Imbruvica is now forecast to be AbbVie's second-biggest seller by 2020.

Venclexta still has a way to go, but the early efficacy signs are positive. Roche and AbbVie will hope that no more safety issues rear their heads.

Selected late-stage Venclexta studies
Regimen Setting Trial ID Notes Primary completion
Venetoclax monotherapy r/r CLL 17p del NCT01889186                 Approved Data reported
Venetoclax + Rituxan r/r CLL NCT02005471 Phase III Sep 2020
Venetoclax + Gazyva 1st-line CLL NCT02242942 Phase III Nov 2018
Venetoclax monotherapy after Imbruvica/idelalisib r/r CLL NCT02141282 Phase II Oct 2017
Venetoclax + Rituxan +/- bendamustine r/r follicular lymphoma NCT02187861 Phase II Mar 2018
Venetoclax + Rituxan/Gazyva + chemo 1st-line non-Hodgkin's lymphoma NCT02055820 Phase II Apr 2018
Venetoclax monotherapy r/r Waldenström macroglobulinaemia NCT02677324 Phase II Feb 2019

To contact the writer of this story email Madeleine Armstrong in London at or follow  @medtech_ma on Twitter

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