No good reaction to Celldex's Act IV

Another cancer vaccine bites the dust. This time it was Celldex's Rintega, the pivotal trial of which was halted for futility in first-line glioblastoma, with the company blaming better than expected survival among control patients.

The setback wipes away any hope that the New Jersey-based biotech will see product sales anytime soon, as follow-on projects are now only in phase II. Today’s announcement also has to shake the confidence of the cancer vaccine faithful, as Rintega had perhaps some of the best data ever coming out of phase II.

Whatever value investors saw in Celldex was mostly baked into hopes that the phase III Act IV trial would be a success. Shares fell 52% to $3.94 in early trading, taking the group’s market capitalisation near to its year-end cash position of $290m; a year ago, the group had been valued at nearly $3bn.

Bull case evaporates

Act IV’s data safety monitoring committee made its call at a second interim analysis, triggered by 75% of the 745 patients in the trial having died. Because the company’s timeline for this analysis had slipped from late 2015, Celldex bulls had argued optimistically that it was because of survival of patients in the active treatment arm of Rintega plus Temodar (Event – Celldex’s second shot at interim halt, February 23, 2016).

The equally plausible explanation, and the one that turned out to be true according to the company, was that control arm patients also had unexpectedly long survival – a numerically longer 21.1 months vs 20.4 months for Rintega. In a conference call today, Celldex executives confirmed that patients randomised to Temodar only outperformed historical and contemporary controls.

Patients from the current and previous trials taking Rintega, along with those taking it on a compassionate use basis, will continue to have access.

Try again?

Failure is a surprise given that in the albeit smaller React trial Rintega managed to eke out a statistically significant overall survival benefit. When combined with Avastin, Celldex’s project generated an 11.6-month survival number compared with 9.3 for Avastin alone.

That was in second-line disease, of course, and with a different backbone medication. This is a hypothesis the company has yet to pursue in a pivotal trial – the hope was for a regulatory filing on phase II data (Celldex chases its tail for cancer vaccine win, November 23, 2015). So Rintega might not be dead just yet, but its runway to market just got much longer – finding the optimal disease state and combination treatment will take time.

The group has a decent pipeline, and in some of the hotter areas of oncology that have generated success like antibody-drug conjugates and immune stimulating antibodies. Rintega might remain an intriguing scientific project, but Celldex very well may want to shift its focus to higher-percentage shots to regain investor interest.

Study Trial ID
Act IV NCT01480479
React NCT01498328

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @ByJonGardner on Twitter

Share This Article