Will the FDA refuse approval in the face of the favourable ODAC 9 versus 1 vote?, page-4

Here is the conclusion from an article that looked at the impact of ODAC deliberations on FDA decisions between January 2009 to December 2019.

Conclusion
Within the FDA’s benefit-risk framework, reviewers evaluate applications to determine that a drug under development is effective and that its expected benefits outweigh its potentialrisks to patients. In addition to the body of evidence presented by sponsors in a New Drug Application (NDA)or Biologics Licensing Application (BLA), this assessment is informed by the severity of the condition for which the drug is being developed, how well patients’ medical needsare being addressed by available therapies, uncertainties around how well premarket clinical trials will translate into real-world use, and the need for risk management tools [23].As part of its statutory commitment, FDA utilizes ACMs to better understand complex therapeutic questions and makeinformed regulatory decisions. In oncology, this has become increasingly important as therapeutic modalities and clinicaltrial design have evolved significantly over the years. Atthe point ODAC meets, FDA in its role as regulatory body has established concerns with the data package. The calling of an ODAC meeting allows the Agency to have a discussion with a body of experts on the clinical significance ofthe therapy in question and its implications to practitioners and patients. Albeit not specific to oncology, historical data tell us that disagreement between Advisory Committees’vote and FDA’s regulatory decisions are uncommon [1, 2,24–26]. Here, we sought to briefly illustrate those occasions.Although ultimately the Agency’s decision is the result of rigorous internal review and assessment of benefit versus risk, there are some key resonating themes observed.

For cases in which FDA’s regulatory decision was less conservative than the ODAC’s, the importance of a clinicallymeaningful effect for patients compared to contemporaneous approved therapies for any given malignancy was acknowledged by the FDA. In such situations, sponsors generallypresent additional data following the AC meeting, withor without FDA meetings, which tend to influence FDA’s decision as seen in the case of selinexor, panobinostat, andolaparib. Additionally, therapies that received approvaldespite a negative ODAC vote were those with a novel MOAand which provide options to refractory patients who areout of treatment options. In light of this, it behooves sponsors to critically evaluate their data and identify the highestunmet medical need subpopulation in whom a positivebenefit-risk ratio is expected. FDA has shown over the yearsthat it is willing to hold discussions with sponsors when the population most likely to benefit is identified. Finally, the Agency and committee members paid attention to regulatoryprecedent; often, discussion was had on the threshold of evidence that previous sponsors had met and how that compared to the case in question.

In cases where FDA took a more conservative approach than the ODAC’s, the inadequacy of clinical trial design and ability of the data to meet FDA’s evidentiary standard wasa common hurdle for sponsors. Factors such as the clinical relevance of the regulatory endpoint, adherence to the prespecified trial protocol, and the integrity of data collected were discussed at length. In line with FDA’s objective touphold patient safety, toxicity was another factor that playsa major role in ODAC discussions and ultimately, FDA’s decision against approval.

Although not legally binding, ODAC’s opinion on a therapyis valued by FDA. The six cases presented offer insights into the circumstances surrounding FDA’s regulatory decisionand the potential rationale that underpin discordance with ODAC’s opinions.