Novartis looking for new homes for midphase asthma, eye disease and NASH assets after pipeline review

Novartis has put (PDF) a trio of midphase drugs up for partnering. After performing its annual portfolio review, the Swiss Big Pharma decided to bring in outside support to drive development of treatments for retinitis pigmentosa, asthma and nonalcoholic steatohepatitis (NASH).

The three candidates on the block are the gene therapy CPK850, the anti-TSLP antibody fragment CSJ117 and the FXR agonist LJN452. All the assets made it as far as phase 2 before Novartis decided to partner.

Novartis developed the sub-retinally delivered gene therapy CPK850 for use in patients with retinitis pigmentosa because of mutations in the RLBP1 gene. The candidate uses the AAV8 viral vector to carry the gene for human RLBP and thereby address the cause of the genetic disease. Novartis moved the candidate into the clinic in 2017 to assess whether it can improve visual function.

The asthma candidate, CSJ117, moved into the clinic in the same year as CPK850. Since then, Novartis has initiated three phase 2 trials to evaluate the inhaled therapy in patients with uncontrolled asthma or chronic obstructive pulmonary disease, establishing itself as a player in a space that has also attracted the attention of Amgen and AstraZeneca, a pair that won approval for their rival TSLP-blocker Tezspire last year.

Novartis has tested the third drug now up for partnering in NASH and primary biliary cholangitis. LJN452, the FXR agonist also known as tropifexor, was once a key pillar of the company’s approach to NASH.

Shortly after taking over as Novartis CEO in 2018, Vas Narasimhan told investors he believed LJN452 had a best-in-class profile that could avoid the itching and cholesterol elevations associated with similar drug molecules, enabling the use of a much higher dose. At that time, LJN452 was Novartis’ lead compound in NASH. The company has terminated two LJN452 studies over the past year.

NASH has been an unforgiving landscape for pharmas big and small, with companies like Bristol Myers Squibb walking away from once promising candidates as the disease refuses to bow to any therapeutics. 

Novartis disclosed the results of its annual portfolio review alongside the news (PDF) that a phase 2 clinical trial of the TIM-3 monoclonal antibody sabatolimab has failed to generate the data needed to support an early submission in myelodysplastic syndromes. Because the readout was “not supportive” of an early filing, Novartis will wait for data from an ongoing phase 3 trial before seeking approval.