Celcuity eyes big market opportunity after breast cancer win

Armed with positive phase 3 results with lead drug gedatolisib in breast cancer, Celcuity is preparing for an FDA filing and possible launch into what could be a blockbuster market.

The results of the VIKTORIA-1 study of gedatolisib, an intravenous PI3K/mTOR inhibitor originally developed by Pfizer, revealed a significant improvement in progression-free survival (PFS) in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer without PIK3CA mutations.

The trial compared a combination of gedatolisib and fulvestrant – with or without Pfizer's CDK4/6 inhibitor Ibrance (palbociclib) – to fulvestrant alone in patients whose cancer had advanced despite earlier treatment with a CDK4/6 blocker or aromatase inhibitor.

With the triple regimen, the risk of disease progression or death was reduced by 76%, and median PFS extended from two months with fulvestrant to more than nine months. Dual therapy with gedatolisib and fulvestrant was nearly as good, reducing the risk by 67% with a median PFS of 7.4 months.

Shares in Celcuity rocketed 168% on the data – giving the Minneapolis-based biotech a valuation approaching $1.4 billion – as the company pointed to an unprecedented benefit for a phase 3 trial in HR+, HER2- advanced breast cancer.

"The topline data for both gedatolisib regimens from VIKTORIA-1 are potentially practice-changing," said co-principal investigator Sara Hurvitz of Fred Hutchinson Cancer Center in the US.

"To my knowledge, we have not seen phase 3 results in patients with HR-positive, HER2-negative advanced breast cancer before where there was a quadrupling of the likelihood of survival without disease progression relative to the study control."

At a stroke, the data gives Celcuity a potential advantage over already-marketed oral PI3K inhibitors like Novartis' Piqray/Vijoice (alpelisib) and Roche's Itovebi (inavolisib), which are currently approved only for PIK3CA-mutated patients, the latter as a first-line option.

PIK3CA mutations are found in approximately 40% of HR-positive breast cancers and are linked to faster tumour growth, disease progression, and treatment resistance.

VIKTORIA-1 includes a cohort of patients with tumours that are PIK3CA-positive and is due to report later this year. Assuming that hits the mark, Celcuity could approach the market with a broad label in the second-line setting, with a filing expected before year-end.

In the meantime, Celcuity is waiting for a readout from a second pivotal trial – VIKTORIA-2 – that is testing front-line gedatolisib in combination with a CDK4/6 inhibitor in patients with and without PIK3CA mutations.

For now, all eyes will be on the presentation of the full VIKTORIA-1 dataset later this year, to see if the efficacy and safety data stand up to scrutiny.

On the tolerability, Celcuity said that discontinuation rates were lower than in other pivotal trials of approved therapies for this form of breast cancer, and had lower rates of the main side effects – hyperglycaemia and stomatitis – that were encountered in its earlier phase 12b study.

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