Novartis has dumped (PDF) its secretive, high-risk, high-reward obesity candidate after emerging from a phase 2 trial with lackluster efficacy. The Swiss drugmaker disclosed the termination alongside news that it is stopping development of a phase 3 pancreatic cancer candidate “based on benefit-risk assessment.”
Talking to investors in February, Novartis CEO Vas Narasimhan, M.D., named the obesity candidate, MBL949, as a high-risk, high-reward program. Narasimhan previously said the molecule has a “unique mechanism of action” and, if the phase 2 readout was positive, could spur a flurry of activity including the progression of earlier-stage candidates, development of combinations and “potential external opportunities.”
Now, disappointing efficacy data have kiboshed Novartis’ plans to put MBL949 at the heart of a broader push into obesity. The Big Pharma disclosed the change in a line in its financial results, revealing that the program was “discontinued due to lack of efficacy.” Novartis completed a phase 2 trial in May.
On an earnings call with analysts this morning, Narasimhan explained that the asset "ultimately did not have a compelling overall profile."
The CEO had previously declined to disclose the molecule’s mechanism of action, only telling investors it is “unique.” The second quarter update lists GDF-15 next to MBL949. GDF-15 has attracted the interest of other companies targeting obesity. Eli Lilly terminated a trial of a GDF-15 receptor agonist in response to “an insufficient benefit/tolerability ratio.” Johnson & Johnson outlicensed a GDF-15 analog in 2021.
On this morning's call, Narasimhan said Novartis does have preclinical programs "looking at novel mechanisms in the preclinical space in obesity and metabolism," but he stressed that these are still at a "very early" stage of development. Instead, when it comes to the cardiometabolic space, the Big Pharma's "focus is cardiorenal," he added.
The other high-profile casualty of Novartis’ second quarter clearout is NIS793. Novartis moved the drug candidate, a TGFB inhibitor also known as niseovkitug, into a phase 3 trial as a treatment for first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) in 2021. The study was scheduled to finish at the start of 2026.
However, Novartis is discontinuing development in mPDAC “based on benefit-risk assessment.” A phase 2 trial in colorectal cancer is continuing. ClinicalTrials.gov lists a colorectal cancer study of NIS793 with a primary completion date of May 2024.
Several other candidates included in the pipeline Novartis published in the first quarter are missing from the latest list of active programs. Fierce Biotech has contacted the company for further information on the status of the programs.