FDA raises questions in adcomm briefing docs for Roche's Polivy label expansion
An FDA advisory committee is meeting on Thursday to weigh a potential label expansion for Roche’s potential blockbuster Polivy, but the agency has some concerns about efficacy and safety.
The pharma giant will come before the Oncologic Drugs Advisory Committee (ODAC) on Thursday to discuss data from the Phase III Polarix trial, originally intended to meet a post-marketing requirement, and see if Polivy can be used for patients with earlier lines of diffuse large B-cell lymphoma (DLBCL).
The drug was first approved back in 2019 under the accelerated approval pathway for patients with relapsed or refractory DLBCL, not otherwise specified (NOS), after at least two prior therapies.
However, FDA dropped a 104-page briefing document that illuminates the agency’s current concerns on the antibody-drug conjugate.
According to the regulator, several concerns related to the Polarix trial include what the agency said was a modest benefit of polatuzumab vedotin (Polivy) plus cancer regimen R-CHP over R-CHOP, another cancer drug regimen — showing a hazard ratio of 0.73. As the agency noted, the point estimates of PFS rates at one and two years were only different by 4.1% and 6.5%, respectively.
“The difference in observed PFS rates is modest, and it is questionable whether this rate of difference is clinically meaningful,” according to the documents. FDA also noted that the PFS benefit did not translate over to a benefit in complete response (CR) rate or overall survival (OS).
Secondly, the FDA pointed out that while the final analysis in OS showed a median follow-up time of 39.7 months, it did not show an improvement for Polivy + R-CHP. On top of that, the hazard ratio in the largest subgroup (DLBCL NOS) was 1.02 — a 2% increased risk of side effects.
“While there is uncertainty associated with the point estimates due to low event rates, lack of improvement in OS, particularly in the context of frontline therapy for LBCL, is a reflection of safety and efficacy and adds to the uncertainties in benefit-risk,” the agency added.
Thirdly, other efficacy endpoints touted in the study have “limitations,” FDA said. One of those endpoints included the difference in complete response rate determined by blinded independent central review, or BICR. The agency said that the difference in CR rate was not statistically significant in either the drug plus R-CHP arm or the drug plus R-CHOP treatment arm, with a p-value of p=0.1557. Further, the agency said the “lack of improvement in CR rate” creates more uncertainty about the efficacy of the treatment, especially in light of the aforementioned PFS benefit.
The Phase III, which enrolled 879 patients, had 740 patients enrolled that had DLBCL NOS.
