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In the News: December 2020 Regulatory and Development Updates

Each month, Camargo’s “In the News” series highlights important changes and advancements in the regulatory and development space and explores how those changes could impact your program.

FDA Issues Advice on Combination Products

In December, the FDA published “Requesting FDA Feedback on Combination Products” to (a) discuss how combination product sponsors can obtain FDA feedback on scientific and regulatory questions and (b) describe best practices for the FDA and sponsors when interacting on these topics. The guidance could also serve as a good regulatory primer for those new to combination products.

The guidance points out the distinction between application-based interactions, such as the formal meeting process used by CDER, and Combination Product Agreement Meetings (CPAMs), the latter having been created via the 21st Century Cures Act.

CPAMs are intended as a means (in addition to the application-based mechanisms) for sponsors to obtain clarity and certainty and are available for combination products for which the lead center assignment is clear. The purpose of a CPAM is to address the standards and requirements for marketing authorization of a combination product and other issues relevant to a combination product, such as requirements related to postmarket modification of the product or CGMPs.

According to the guidance, sponsors should generally use application-based mechanisms to request feedback on scientific issues, study design, testing approaches, or application preparation considerations for combination products or to gain clarity on topics for which the FDA has already published guidance. On the other hand, sponsors should use CPAMs to seek agreement from the FDA on an approach if previous feedback under an application-based mechanism has not provided enough certainty. CPAMs should not be used to resolve disputes that fall under the lead center’s dispute resolution or appeals process.

If you are developing a combination product, Camargo can help you design the fastest, most efficient path to approval.

Approval of the Month: FDA Clears Orladeyo from Biocryst Pharmaceuticals

The FDA approved Biocryst Pharmaceuticals Orladeyo (berotralstat) 100 mg and 150 mg capsules for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older. According to the FDA, HAE is an orphan disease that affects an estimated one in 10,000-50,000 people worldwide (approximately 6,000-10,000 in the United States). Acute attacks of HAE are potentially life-threatening, particularly in cases of laryngeal edema resulting in airway compromise. Attacks at other anatomic sites can cause disabling pain and significant morbidity.

Orladeyo is a new molecular entity (NME) with orphan drug designation that is not approved elsewhere in the world. Most approvals for NMEs require two well-controlled studies, but since HAE is a rare disease, the FDA approved Orladeyo based on a single 24-week pivotal trial in adolescents and adults. Due to the challenges of recruiting these patients, the FDA also allowed patients from Phase 1 and Phase 2 trials to participate in the pivotal study.

Studying two doses in the pivotal study presented another challenge for the sponsor. If one dose had not been not efficacious, it is possible Biocryst would not have been able to obtain sufficient safety information (this drug will be dosed for the life of the patient). In the end, the FDA approved a dosing regimen of a recommended starting dose of 150 mg once daily and 110 mg once daily for patients with moderate-to-severe hepatic impairment or for patients with persistent gastrointestinal adverse reactions.

Clinical trial design for a rare disease requires a customized, creative approach. Camargo has extensive experience in the development and approval of drugs with a single pivotal study. Contact us to learn how we can advance your orphan drug program.

FDA Clarifies Policies on CRLs, Inspections, and COVID-19

In our November edition of In the News, we noted several issues connected with delays in FDA facility inspections for NDA (as well as ANDA and BLA) applicants. In late December, FDA issued a new guidance titled “Review Timelines for Applicant Responses to Complete Response Letters When a Facility Assessment Is Needed During the COVID-19 Public Health Emergency.”

The guidance addresses the FDA’s review timelines during the COVID-19 public health emergency for applicant responses to complete response letters (CRLs) when a facility inspection or assessment is necessary before the FDA can take action on a marketing application. Where a regulatory decision is needed that (a) requires an inspection that cannot be conducted in a timely manner because of COVID-19 or (b) involves the use of time- and resource-intensive alternative tools to assess a facility or BIMO site, the following will apply:

  • Resubmissions of original applications and efficacy supplements for NDAs and BLAs will be subject to a Class 2 review timeline of 6 months.
  • Amendments to both original ANDAs and prior approval supplements to approved ANDAs will be received as a major amendment and will be reviewed per the guidance “ANDA Submissions—Amendments to Abbreviated New Drug Applications Under GDUFA,” regardless of whether the CRL contains a major deficiency.


Ken Phelps
President and Founder

Bill Stoltman, JD
Vice President, Regulatory Operations