The deal’s termination was announced Thursday, months after bintrafusp alfa failed to hit the mark in a Phase II clinical trial as a potential second-line treatment for metastatic biliary tract cancer.
After two years and multiple trial failures, Merck KGaA, Darmstadt, Germany and GlaxoSmithKline have terminated a nearly $4 billion development agreement that centered on the experimental immunotherapy drug bintrafusp alfa.
The termination of the deal was announced Thursday, months after bintrafusp alfa failed to hit the mark in a Phase II clinical trial as a potential second-line treatment for metastatic biliary tract cancer (BTC). That trial failure in patients who have either failed or are intolerant to first-line platinum-based chemotherapy followed a decision made by the two companies to discontinue the development of bintrafusp alfa as a first-line therapy for patients with stage IV non-small cell lung cancer (NSCLC) and high expression of PD-L1.
The asset was in Phase III development when the companies pulled the plug following a recommendation from the Independent Data and Safety Monitoring Board. In that trial, bintrafusp alfa was paired with Keytruda, a checkpoint inhibitor developed by the U.S.-based Merck. The board recommended trial termination after a review determined the study was not likely to meet its primary endpoint of progression free survival.
Bintrafusp alfa is an investigational bifunctional fusion protein immunotherapy. Merck KGaA and GSK initially hooked up to develop the asset in 2019. The goal was to aim the experimental treatment at multiple cancer indications that are considered difficult to treat.
When the companies signed the developmental collaboration for bintrafusp alfa, GSK made an upfront payment of €300 million (about $445 million) to Merck KGaA. Additional milestone payments of up to €2.9 billion ($3.4 billion) were to have been made. However, because bintrafusp alfa failed to meet milestone goals, Merck KGaA said no additional payments were made to the company, and no future obligations remain that are related to this deal.
The decision to terminate the partnership is a particularly tough blow to GSK and embattled Chief Executive Officer Emma Walmsley as the company moves to split into two entities, a more nimble pharmaceutical company and a consumer healthcare business.
With her extensive background in consumer health products, which includes leading GSK’s own consumer health division as well as a 17-year stint at L’Oréal, Walmsley has been under fire from multiple GSK stakeholders for her leadership of the pharma business. The primary charge against her is that she lacks the scientific background necessary to lead a pharmaceutical company.
Although Walmsley has been under fire from activist investor groups Bluebell Capital Partners and Elliott Management, the company board of directors has stood behind its decision to keep Walmsley as CEO. The company split is set for mid-2022. This past summer, Walmsley outlined the projected de-merger of the two GSK businesses. As BioSpace previously reported, the pharma-focused business, dubbed New GSK, has projected revenue of approximately $46 billion by 2031.
Following the merger, New GSK will maintain a focus on the four core therapeutic areas of HIV, infectious disease, immunology/respiratory and oncology. The company’s vaccines business is expected to be a key driver, alongside its specialty medicines business. GSK has 20 different vaccine candidates in its pipeline, as well as its adjuvant pandemic technology.
New GSK also has 42 specialty medicines in development. When looking at both pipelines, the company predicted that a high number of those assets provide potential best- or first-in-class opportunities.
For Merck KGaA, which developed bintrafusp alfa, the company said the trial failures deepen its understanding of TGF-β and will help guide its future development of therapies targeting this pathway.
