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CRITical Thinking is a blog written by staff, directors, and friends of the Collaboration for Research Integrity and Transparency (CRIT), a joint program of Yale Law School, Yale School of Public Health, and Yale School of Medicine. CRIT's mission is to promote health by improving the integrity and transparency of biomedical and clinical research.

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Federal Judge Rules in FDA's Favor in Dispute Over Pediatric Exclusivity: A Win for the Agency, Patients, and Clinical Evidence

February 21, 2018

On February 17, 2018, a federal judge in the D.C. District Court affirmed the U.S. Food and Drug Administration's decision to deny a six-month extension of market exclusivity for Amgen's blockbuster drug cinacalcet (Sensipar). Commonly used for patients with end-stage kidney disease, cinacalcet is one of Amgen's most profitable drugs and generated $1.37 billion in U.S. sales in 2017. The court's decision now clears the path for generics to enter the market as early as next month, when cinacalcet's main patent expires.1

Beyond the immediate benefits of lowering the price of cinacalcet for patients, the decision has broader implications for the FDA's ability to administer the pediatric exclusivity program—a powerful financial incentive for pharmaceutical companies to conduct pediatric research. By ruling for the FDA, the judge preserved the agency's authority and discretion to make pediatric exclusivity determinations in a way that encourages clinically meaningful research.

At issue in the case was the FDA's interpretation of the statutory standard for granting pediatric exclusivity—whether the sponsor's pediatric studies "fairly respond" to the agency's request for the studies. In May 2017, the FDA had denied pediatric exclusivity for cinacalcet because it found that Amgen's pediatric trials did not fulfill the enrollment criteria and did not otherwise meet the objectives specified in the written request. The studies yielded inconclusive safety results and thus, did not produce information that was clinically meaningful for the relevant pediatric population.

Amgen brought a lawsuit to challenge the denial and notably, the FDA's interpretation of the "fairly respond" standard. The company argued that the standard is agnostic to the scientific value of the studies and only requires that the sponsor meet most of the terms (numerically speaking) specified in the request.

While the case was pending, Yale CRIT fellow Jeanie Kim and faculty co-directors Amy Kapczynski and Joseph Ross wrote a viewpoint for JAMA. We supported the FDA's "clinically meaningful" interpretation. Such an interpretation ensures that the FDA can apply its scientific expertise to determine which studies meet its evidentiary standards and are likely to provide useful pediatric data. Furthermore, Amgen's interpretation would create disincentives for rigorous pediatric clinical trials, defeating the purpose of the pediatric exclusivity program to meet a research need.

On January 26, 2018, the court ruled in the FDA's favor, deferring to the agency's interpretation of the "fairly respond" standard. The judge found that it is reasonable for the agency to evaluate whether the studies were designed and conducted to produce meaningful safety and efficacy data for pediatric patients in light of Congress' purpose for establishing the pediatric exclusivity program—to address the lack of information about pediatric uses of drugs.

The court did send the case back to the FDA to resolve a narrower issue. Amgen had also argued that even if the FDA's interpretation is sound, the agency applied the standard inconsistently in denying pediatric exclusivity to cinacalcet while granting the exclusivity to Johnson & Johnson's Ortho Tri-Cyclen (OTC) in 2003.

However, after giving the FDA a chance to offer an explanation, the court determined, in its latest decision, that the FDA had a reasonable basis for the disparate treatment. The FDA found that Amgen's studies simply failed to enroll the minimum number of participants to yield reliable data. On the other hand, Johnson & Johnson's studies fulfilled the minimum number of participants by using inclusion criteria that, while not exactly the same as the terms of the request, was an acceptable surrogate that fulfilled the purpose of the request.

Under the "fairly respond" standard, the judge found that it is well within the FDA's authority to make such a determination in accordance with its scientific judgment:

"Whether the FDA was, in fact, correct in determining that the Ortho Tri-Cyclen study subjects met the [enrollment] criteria is not the relevant question. All that matters for the present purposes is whether the FDA applied an interpretation of 'fairly respond' to Amgen that differed from the standard it applied to Johnson & Johnson, and the agency has reasonably explained that it did not do so." Amgen Inc. v. HHS, No. 17-cv-01006-RDM, at 11 (D.D.C. Feb. 17, 2018).

By assessing the quality of clinical studies, the FDA can uphold the strong public interest in ensuring that, in exchange for the commercial advantage of extending market exclusivity, companies conduct robust studies that are likely to guide clinical decision making for pediatric patients.

Amgen immediately appealed the case to the D.C. Circuit Court. With the main patent for cinacalcet set to expire on March 8, 2018, the appellate court will likely be making its decision soon.


1  However, Amgen's patent for the rapid dissolution formulation of cinacalcet does not expire until 2026. See a list of exclusivities related to cinacalcet.