Halozyme drops PFS co-primary endpoint from PEGPH20 phase 3

Halozyme has dropped the progression-free survival (PFS) co-primary endpoint from its phase 3 trial of PEGPH20 in metastatic pancreatic cancer. The change ties the fate of the trial to an overall survival endpoint that is expected to read out in the second half of 2019.

When Halozyme designed the HALO-301 trial, it persuaded the FDA to sign off on a design featuring co-primary endpoints. The plan was to test the effect of Halozyme’s pegylated form of recombinant human hyaluronidase on PFS at an interim analysis, before going on to collect the OS data needed to win a full approval.

“Our rationale was that if the FDA would grant an accelerated approval based on progression-free survival, PEGPH20 could be available to patients significantly earlier,” Halozyme CEO Helen Torley said on a conference call with investors to discuss the change. 

However, the prospect of getting PEGPH20 to patients “significantly earlier” on the strength of PFS data has waned since the trial began. The trial was due to deliver PFS data in April but a higher than expected rate of censoring—40%—pushed back the readout. Halozyme incorporated PFS censoring into the trial to reduce the risk that patients who change drug mid-study will confound the analysis.

The upshot is that whereas Halozyme originally expected to have PFS data 16 months before the OS readout, the lag may now be as little as six months. Halozyme framed that change in expectations as the motivation for the move to a single OS primary endpoint.

“As part of finalizing the statistical analysis plan, we consulted with several statistical and regulatory advisors. [They] recommended pursuing a potentially better option of analysing overall survival as the only primary endpoint of the study, given what they and we noted was a much shorter interval between the time to PFS and OS events than we had originally projected,” Torley said.

The feedback prompted Halozyme to approach the FDA about changing the endpoints. The FDA is yet to review the amended protocol and statistical plan, but Halozyme said the agency thinks the aspects of the plan it has seen look to be acceptable. That emboldened Halozyme to unveil the change.