How Data Packages Lacking Phase III Pivotal Trial Data Can Support Regulatory Approval and Reimbursement for...

Oncology drugs lacking supportive phase III trial data have achieved Food and Drug Administration (FDA) and European Medicines Agency (EMA) regulatory approval and even European reimbursement approval where no therapeutic alternative exists and early-stage data indicate dramatic clinical benefits.

This research aimed to compare under what circumstances oncologics can obtain both regulatory and reimbursement approval in Australia on this basis.

Therapeutic Goods Administration (TGA) Australian Public Assessment Reports, EMA, FDA, and Pharmaceutical Benefits Advisory Committee (PBAC) Public Summary Documents were extracted for any oncologic indication appraised in Australia on a pivotal trial package lacking phase III data, excluding pediatric indications and new formulations.

Australian Public Assessment Reports were available for six TGA-appraised oncologics across seven indications on such a data package: five of seven approved, one of seven restricted, and one of seven rejected. The EMA and the FDA issued recommendations on these indications an average of 1 and 2 years earlier, respectively. The PBAC appraised six oncologics across 10 indications on such a data package, with four (nilotinib, dasatinib, imatinib, and brentuximab vedotin) approved and two rejected (cetuximab and bevacizumab). Seven of the eight approved indications required multiple submissions, with inadequate clinical data frequently cited as key. Six of the eight PBAC-approved indications included economic modeling on a cost-benefit approach.

The TGA will approve oncologics that offer potentially substantial clinical benefits on the basis of an indirect comparison of single-arm trials but at a delay versus the EMA and the FDA. The PBAC reimbursement approval also requires more rigorous supportive clinical data and acceptable cost-effectiveness as demonstrated on a cost-benefit or cost-quality-adjusted life-year metric.