ASCO26: Celcuity punished as trial disappoints investors

Celcuity is still confident it is on to a winner with its breast cancer treatment, gedatolisib, but a much-anticipated readout at ASCO led to a backlash from investors and a sell-off of its stock.

Gedatolisib is a PAM pathway inhibitor – combining PI3K and mTOR inhibition in one molecule – and in the VIKTORIA-1 trial was given as a triple therapy (with Pfizer's CDK4/6 inhibitor Ibrance and aromatase inhibitor fulvestrant) or a dual therapy (with fulvestrant) in HR-positive, HER2-negative breast cancer driven by PIK3CA mutations.

The triplet reduced the risk of disease progression or death by 50% compared to Novartis' PI3K inhibitor Piqray (alpelisib) plus fulvestrant, with a median progression-free survival of 11.1 months and 5.3 months, respectively. The doublet also did well, reducing PFS by 49% to 11.3 months.

Despite that strong result, shares in the company fell more than 25% after the data was presented at ASCO, suggesting investors were disappointed by the scale of the improvement in OFS on display compared to earlier clinical trial results.

Celcuity, which revealed earlier this year that gedatolisib had outperformed Piqray in the study, said the PFS result came in ahead of its internal expectations, and the company also emphasised the tolerability compared to Novartis' drug and a very low discontinuation rate.

"It is rare in oncology for a targeted therapy to offer both improved efficacy and better safety results relative to another drug in its class," said chief executive and co-founder Brian Sullivan.

Knee-jerk reactions to positive data emerging on much-anticipated new therapies aren't unusual, as seen with Abivax, which plummeted this week on data for its ulcerative colitis candidate before recovering some of the lost ground, so it will be interesting to see if there is a correction to Celcuity's share price in the coming weeks. The stock had regained almost 3% pre-market at the time of writing.

There's a major inflection point for the stock coming in mid-July, when the FDA is expected to deliver a verdict on gedatolisib's filing for HR+/HER2-, PIK3CA wild-type advanced breast cancer, currently under priority review. That marketing application is also based on the VIKTORIA-1 trial.

Based on the new data, gedatolisib should be approvable as a broadly-acting drug in both wild-type and mutant forms, while current PI3K inhibitors, such as Piqray and Roche's Itovebi (inavolisib), are currently only indicated for PIK3CA-mutant disease.

Sara Hurvitz of the Fred Hutchinson Cancer Center, a co-principal investigator for VIKTORIA-1, said that therapies targeting only PI3K or AKT typically offer modest benefit for patients with this type of breast cancer in the second-line setting.

"Gedatolisib combined with fulvestrant, with or without palbociclib, showed it can offer these patients two times the likelihood of survival without disease progression or death relative to a single-target inhibitor of the PAM pathway," she asserted.

"The gedatolisib regimens, if approved, represent a new potential standard of care."

Celcuity has previously said that approval in the second-line setting alone would unlock a $5 billion potential market for gedatolisib.