GSK kicks out of Wave's AATD programme

Wave Life Sciences has lost GSK as the partner for its RNA-editing drug for alpha-1 antitrypsin deficiency (AATD), just over three years after the pharma group paid $170 million upfront for rights to the programme and other candidates.

In a statement, Cambridge, Massachusetts-based Wave said that while GSK is no longer interested in lead candidate WVE-006, their partnership remains active with four other programmes now being taken forward.

The original alliance covered up to eight preclinical projects, and the company suggested GSK now wants to focus more on "large-scale diseases," rather than rare conditions.

AATD is an inherited disorder whose primary consequence is life-threatening pulmonary emphysema, resulting in irreversible destruction of the tissues supporting the function of the lungs. It also causes damage to the liver. There are an estimated 200,000 individuals living with AATD in the US and Europe with the genetic form of the disease – homozygous for the 'ZZ' mutation – that is targeted by WVE-006.

The decision to dissolve the partnership on WVE-006 comes despite encouraging results from the phase 1b/2a RestorAATion-2 trial of the therapeutic in 2024, which Wave trumpeted as the first clinical data with a therapeutic RNA-editing drug in humans.

Since then, the study has generated further positive data at multiple dose levels, showing that the drug can raise levels of wild-type ATT and reduce levels of the mutated, inactive form. New data from the next cohort of patients in RestorAATion-2 is due in the coming weeks.

Wave has pitched GSK's decision not to continue with WVE-006 as an opportunity to speed up "regulatory engagement" for the therapy as it seeks a green light from the FDA for an accelerated approval pathway. It said it is hoping for feedback from the agency on that in the middle of this year.

"AATD is one of the largest rare disease indications and the 200,000 individuals in the U.S. and Europe living with homozygous 'ZZ' AATD face extremely limited treatment options," said Wave's president and chief executive, Paul Bolno.

At the moment, weekly intravenous augmentation therapy using plasma-derived AAT is approved for the lung complications, but there are no treatments available for AATD liver disease, he added.

"WVE-006 is well-suited to Wave's strengths and ability to execute on a commercial strategy. We look forward to engaging with regulators on how to rapidly advance this potentially transformative, first-in-class therapy to address both lung and liver manifestations with convenient, infrequent subcutaneous dosing."

Also this week, GSK said it would cut 350 jobs from its R&D workforce as new chief executive Luke Miels starts to ring the changes at the pharma group.

Miels has made growing the company's pipeline a priority, and last month – shortly after he took the helm – it reached a $2.2 billion deal to acquire food allergy biotech RAPT Therapeutics.

Photo by Gabriel Bezerra on Unsplash