FDA Implements FDARA Provision on Orphan Drug Clinical Superiority Determinations

Obtaining FDA decisions detailing when one orphan drug has been determined by the Agency to be “clinically superior” to another orphan drug – either to obtain approval of a product notwithstanding another company’s orphan drug exclusivity for the same drug for the same indication, and/or to obtain a separate period of orphan drug exclusivity – has historically been a bit of a task. First, we members of the public had to comb through FDA’s Orphan Drug Designations and Approvals Database to identify instances in which clinical superiority based on greater efficacy, greater safety, or a major contribution to patient care might have been an issue.  Then we had to submit – and wait for FDA to respond to – a Freedom of Information Act request to obtain FDA’s letter decision and orphan drug designation package.  The fruits of our labor are apparent in various FDA Law Blog posts that compile and categorize FDA’s various orphan drug clinical superiority decisions – see here, here, and here.  But those days of research and waiting might now be behind us!

As we previously noted in a summary memorandum, the 2017 FDA Reauthorization Act (“FDARA”) amended the FDC Act – and the Orphan Drug Act in particular – to add Section 527(e), which states:

(e) DEMONSTRATION OF CLINICAL SUPERIORITY STANDARD.— To assist sponsors in demonstrating clinical superiority as described in subsection (c), the Secretary—

(1) upon the designation of any drug under section 526, shall notify the sponsor of such drug in writing of the basis for the designation, including, as applicable, any plausible hypothesis offered by the sponsor and relied upon by the Secretary that the drug is clinically superior to a previously approved drug; and

(2) upon granting exclusive approval or licensure under subsection (a) on the basis of a demonstration of clinical superiority as described in subsection (c), shall publish a summary of the clinical superiority findings.

It’s FDC Act § 527(e)(2) that really got us excited! (Yes, this blogger gets excited about that kind of stuff.)  We had to sift through FDA’s website to find out how the Agency implemented the new statutory requirement, but we finally found a website titled “Clinical Superiority Findings.”  As of now, FDA’s website identifies only a single clinical superiority determination.  That determination concerns MYLOTARG (gemtuzumab ozogamicin), and it’s a greater safety clinical superiority determination:

The new approval for Mylotarg is for a lower dose and different schedule than the previous approval. In a cross-study analysis of clinical outcomes for patients with relapsed or refractory acute myeloid leukemia treated with single-agent Mylotarg, in comparison to the regimens using the previously approved regimen, patients treated with the new dosing regimen had less early mortality, less hepatotoxicity, less veno-occlusive disease, more rapid platelet recovery and less hemorrhage.  Therefore, the sponsor has demonstrated that the newly approved dosing regimen is safer than the previously approved dosing regimen, and thus clinically superior for the purposes of orphan-drug exclusivity.  21 CFR 316.3(b)(3), 316.34(c).

New clinical superiority determinations will be added as they are made by FDA. As for previous determinations, we assume that FDA will not add those to the website.  So, you’ll have to refer back to our previous postings for descriptions of those precedents.