In a surprise move this week, the US Food and Drug Administration (FDA) approved Farydak®, despite the 5-2 vote by the FDA’s Oncologic Drugs Advisory Committee (ODAC) recommending against approval in November 2014. The approval is obviously good news for the myeloma community. There is an unmet need for new active agents.

It appears that the FDA circumvented the prior controversy regarding less than impressive efficacy and some serious toxicities by focusing on a pre-specified subset analysis of patients treated previously with bortezomib and an iMiD (thalidomide and/or Revlimid ®). For these 193 patients, the median progression-free survival (PFS) was 10.6 months for the panobinostat combination versus 5.8 months with placebo: a 4.8 month advantage. This trumped the prior numbers which ranged from 1.7 to 3.9 months of PFS benefit. The overall response rate was also higher: 59% versus 41%.

The FDA handled the serious toxicity aspect using a “Boxed Warning” approach with a specified Risk Evaluation and Mitigation (REMS) plan for severe diarrhea and potential severe and fatal cardiac events, arrhythmias and ECG changes. The side effect profile is thus acknowledged with warnings about how to best prevent or alleviate these problems.

The willingness of the FDA to consider Farydak® in this fashion is very positive, I think, as it makes agents available that confer some benefit in the randomized trial setting as long as use is accompanied by careful risk assessment. This is preferable to either disapproval or a much looser “compassionate use” protocol prior to adequate efficacy/risk evaluation, such as what is proposed in the so-called “Right to Try” legislation that has passed in some states. So, kudos to the FDA for choosing this middle ground and trusting the treating physician to be aware of the efficacy profile and the “Boxed Warnings.” It is certainly hoped that judicious dose reductions of panobinostat as needed will be accompanied by retained efficacy and a reduced side effect profile.

For relapsed patients, each new response is a blessing; each new response is a bridge to further new options. Let’s be optimistic that several new agents in the pipeline will likewise receive approval and be available in the most appropriate relapse niche. 

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Comments

I have afib issues with Velcade, cynic, Dex. Nothing new here!

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