Idera Pharmaceuticals’ TLR9 agonist has failed to improve on Yervoy in a phase 3 melanoma trial. The miss on the objective response rate endpoint sent shares in Idera down 55%, but the biotech is yet to give up on the drug.
Tilsotolimod, then known as IMO-2125, entered the spotlight in 2017 when Idera reported responses in four of the nine patients who received the TLR9 agonist in combination with Bristol Myers Squibb’s anti-CTLA-4 antibody Yervoy. The patients were refractory to anti-PD-1 checkpoint inhibitors, raising hopes tilsotolimod could treat the sizable number of people who progress despite receiving Keytruda or Opdivo.
The halving of the response rate in a larger phase 2 dampened expectations. Now, the phase 3 data have dealt another blow to the prospects of tilsotolimod. The objective response rate in patients who received tilsotolimod and Yervoy was 8.8%, versus 8.6% in people who only got Bristol Myers’ drug.
Idera reported a numerical improvement in the disease control rate—34.5% versus 27.2%—but that figure was still well down on the phase 2 finding. The setbacks leave Idera looking to the overall survival data for a chance to salvage something from the phase 3. Overall survival is the co-primary endpoint. If tilsotolimod betters Yervoy by that yardstick, Idera could still have a path to market.
The phase 3 investigators are continuing to gather overall survival data. Idera is also forging ahead with a phase 2 study that is giving tilsotolimod in combination with Opdivo and Yervoy. The phase 2 trial is enrolling patients with microsatellite-stable colorectal cancer.
Idera moved tilsotolimod into and through the clinic based on evidence that intratumoral injections of the TLR9 agonist activate the innate and adaptive immune systems. As lack of immune infiltration limits the efficacy of checkpoint inhibitors, Idera and others groups posited TLR9 agonists could bring the strong responses to drugs such as Keytruda seen in some people to more cancer patients.
The failure of tilsotolimod in the phase 3 trial puts a dent in that theory. Checkmate Pharmaceuticals, Dynavax and Exicure are among the other companies working on TLR9 agonists. Shares in Checkmate and Exicure fell slightly in premarket trading.