CBER’s New Director 'Marks' New Era For Biologics Regulation

Peter Marks takes over top spot in FDA's center for biologics after four-year training period as deputy director; his background appears well suited to what promises to be a transformative era in medicine.

New Center for Biologics Evaluation and Research Director Peter W. Marks ascends to the top spot at the center after a nearly four-year training/transition period as deputy director to the former CBER head, Karen Midthun.

Midthun announced her retirement after nearly seven years as acting and permanent CBER director in the early autumn (Also see "Help Wanted: FDA Recruiting New CBER Director Ahead Of Gene, Cell Therapy Wave" - Pink Sheet, 14 Oct, 2015.).

The fast transition to her deputy as permanent successor should provide a smooth, uneventful leadership change. Midthun similarly had taken over the office from the deputy position in 2009 when Jesse Goodman moved to the commissioner’s office as chief medical officer. However, Midthun had a 16-year career at CBER before moving up to be deputy director. Marks joined FDA in 2012 from a teaching/clinical practice position at Yale.

Marks takes over on the cusp of some potentially important regulatory pathway issues for CBER relating to new gene-editing, stem cell and microbiome approaches to treatments.

CBER Director Peter W. Marks

The new issues facing Marks and CBER were highlighted recently in a Jan. 10 speech to the International Society of Stem Cell Research by former FDA deputy commissioner Scott Gottlieb (American Enterprise Institute).

Gottlieb argues that the advent of the new cell-based technologies provides an opportunity for FDA “to adopt a more holistic approach to organizing its regulatory activities.” He contends that “FDA needs to more actively consider moving its regulatory processes away from a mostly clinical orientation and toward one that ties its regulatory functions more closely to the product-specific issues as well as the nature of the risk that the agency is grappling with.”

Gottlieb says that CBER has traditionally taken a more product-oriented approach to regulation. “FDA’s biologics does operate with much more flexibility to how it structures its regulatory approach than the agency’s drug center,” Gottlieb said.

CBER “already takes a more product-specific orientation to its review functions in these areas.” Gottlieb added, however, that “my observation” on the dominance of clinical issues to product-specific issues “is still generally true.”

Gottlieb’s comments suggest substantial outside pressure in the near-term on FDA and CBER to develop different platform approaches to regulation of the new cell-based technologies versus the current premarket focus on demonstrating clinical benefit in a wide array of different uses.

That pressure would be more acute in a Republican administration – particularly one that would rely on Gottlieb as an advisor or potentially as an FDA commissioner.

FDA Sees Gene Editing Fitting Into Current CBER Paradigm

Short of a significant overhaul of CBER’s approach to the new technologies (which is not likely to arise organically within FDA), the key tasks for a Marks-led CBER will be to identify the specific groups within the center that will take the lead on new technologies and how those groups will collaborate with the Center for Drug Evaluation and Research on the clinical reviews related to new technologies.

CBER views gene-editing products as part of the broader gene therapy class. A CBER spokesperson says that “products using gene-editing technologies that edit the human genome are not regulated differently from other gene therapy products.”

The center has been active in guidance in that area and notes two recent guidances in June (“Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products”) and August (“Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products”), the spokesperson notes.

The importance of the evolving regulatory pathway effort to the nascent technologies is demonstrated in the description of the regulatory risks facing the early CRISPR (clustered, regularly interspaced short palindromic repeats) commercialization efforts (Also see "J.P. Morgan Notebook, Jan. 13: Regeneron, AstraZeneca, CRISPR And Juno" - Pink Sheet, 14 Jan, 2016.).

The preliminary IPO prospectus from Editas Medicine Inc. addresses the regulatory pathway risk for its CRISPR/Cas9 approach to addressing genetic mutation conditions. Leber Congenital Amaurosis type 10 blindness is the first target for clinical development.

Editas identifies CBER’s Office of Cellular, Tissue and Gene Therapies and the associated Cellular, Tissue and Gene Therapies Advisory Committee as the loci of FDA control over its technology. In IPO-cautionese, the company acknowledges that the eventual pathway to commercial use is likely to evolve with more complexity.

“The regulatory requirements that will govern any novel genome editing product candidates we develop are not entirely clear and may change,” Editas says.

“Within the broader genome medicine field, only one gene therapy product, uniQure NV's Glybera, has received marketing authorization from the European Commission, and no gene therapy products have received marketing approval in the United States. Even with respect to more established products that fit into the categories of gene therapies or cell therapies, the regulatory landscape is still developing.”

Editas observes that “regulatory requirements governing gene therapy products and cell therapy products have changed frequently and will likely continue to change in the future. Moreover, there is substantial, and sometimes uncoordinated, overlap in those responsible for regulation of existing gene therapy products and cell therapy products.”

Coordination With CDER Will Be Critical

Based on previous experience with overlap technologies such as cancer vaccines and other oncologic biologics, at a minimum there will need to be coordination with the clinical review specialties that reside in CDER, such as ophthalmology for a blindness product.

From the perspective of the potential to co-operate across centers, Marks’ extensive background in academic medicine at Brigham & Women’s and Yale and his specialties in hematology and medical oncology should be a positive.

The academic orientation aligns him with the current tilt from the commissioner’s office and at CDER’s Office of Hematology and Oncology Products for emulating the academic sector in tone and drawing from it for recruitment.

FDA Commissioner nominee Rob Califf (previously Duke vice chancellor) has been emphasizing a renewed agency commitment to strong relations with academic medicine at events like a Grand Rounds at Cleveland Clinic on Jan. 13.

OHOP Director Richard Pazdur recently talked publicly about how he has recruited from academia and created an academic-style environment as part of the change in tone and efficiency in the CDER oncology review area (Also see "FDA Talent Hunt: Is Recruiting From Academia Better Than Industry?" - Pink Sheet, 30 Nov, 2015.).

Marks will fit that model. His specific background is in hematology and oncology and his clinical experience with patients with benign and malignant hematologic disorders – which makes him well versed for the important overlap and collaboration areas with CDER.

That hematology/oncology bond may prove to be more important to the development of a workable and positive regulatory pathway for the new cell technologies through FDA than having a head of CBER with extensive experience in the new technologies themselves.

Prior Industry Experience

The new CBER director also has experience working within industry, though his short biographies for CBER and his previous positions at Yale play down that period of his career.

FDA's bio of Marks describes the years between Brigham & Women’s and teaching and practicing at Yale as entailing work “in the pharmaceutical industry on the clinical development of several different drugs for patients with blood diseases and cancer.”

Marks does not name his corporate affiliations in published bio sketches and FDA declines further identification of his affiliation without a formal Freedom of Information Act request. However, several articles in hematology were published in major journals around 2004, by Peter W. Marks, a research scientist at Novartis AG.

“Peter Wayne Marks” also is listed in 2008 as an inventor on a method of use patent (20080255029) assigned to Novartis for neuroendocrine tumor treatment with an mTOR inhibitor. Novartis' Afinitor (everolimus) is an mTOR inhibitor first approved by FDA in 2009.

At least one previous head of biologics at FDA was an inventor for patent. Harry Meyer, who was head of the Bureau of Biologics in the 1970s and the combined drugs and biologics operations in the mid-1980s, was a co-developer of the strain that led to the rubella vaccine. He held a patent (assigned to the US government) on the detection of rubella by hemagglutination-inhibition.

[Editor's note: This article is also published in The RPM Report. "The Pink Sheet" brings selected complementary coverage from sister publications to subscribers.]