FDA Initiatives Advance Orphan Therapies


Applied Clinical Trials

Applied Clinical TrialsApplied Clinical Trials-11-01-2018
Volume 27
Issue 11

FDA initiatives aim to increase biomarkers and early advice to sponsors for more efficient and cost-effective clinical trials for developing targeted therapies, including orphan therapies.

Jill Wechsler

Streamlined clinical trials and continued patient involvement in product research continue to advance the development and market approval of more innovative therapies for rare conditions. FDA has approved more than 60 orphan indications for new and existing products this year, building on 80 approvals for 2017, according to a study from the IQVIA Institute for the National Organization for Rare Disorders (NORD) (see https://www.iqvia.com/institute/reports/orphan-drugs-in-the-united-states-growth-trends-in-rare-disease-treatments?utm_campaign=2018_InstituteFallReports_Insititute_HF&utm_medium=email&utm_source=Eloqua&utm_campaign=2018_InstituteFallReports_Insititute_HF&utm_medium=email&utm_source=Eloqua). FDA approvals of new treatments are “shattering previous records” based on continued innovation in research in this area, observed NORD President Peter Saltonstall in conjunction with NORD’s annual Rare Disease Summit in Washington, D.C. in October.

Important FDA initiatives aim to increase the use of biomarkers and provide early advice to sponsors to make clinical trials more efficient and less costly for developing targeted therapies, including those for rare conditions. An important draft guidance issued in October encourages sponsors to use “minimal residual disease” (MRD) as a biomarker in testing drugs or biologics to treat certain blood cancers (https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM623333.pdf). This general measure of tumor burden in clinical trials, observed FDA Commissioner Scott Gottlieb in announcing the advisory, has the potential to expedite product development by assessing a patient’s response to treatment or the risk of future relapse. The policy supports using MRD to enrich clinical trial populations and define treatment arms, with an eye to further developing the marker as a surrogate endpoint.

The agency also finalized a guidance on identifying treatments that address underlying factors that may contribute to disease, such as rare molecular changes present in small subsets of patients (https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM588884.pdf). This advisory aims to help sponsors enroll in clinical trials those patients with genetic markers that indicate likely response by providing

information on grouping patients with different molecular alterations and on strategies for evaluating the benefits and risks of targeted therapies to treat diseases with rare molecular alterations.


More support

Sponsors, researchers, and patients can obtain advice and information through a new FDA web portal on “developing products for rare diseases,” which aims to provide a “central home” on FDA regulatory initiatives and programs in this area (https://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/default.htm). A guidance published earlier this year, moreover, clarifies FDA’s orphan drug designation process, which opens the door for sponsors to gain expedited reviews and financial support for clinical studies and other processes (https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM589710.pdf). To help shape early R&D programs for therapies for rare diseases, FDA is encouraging sponsors to sign up for pre-investigational new drug (IND) meetings to discuss studies that utilize smaller patient pools. Another FDA guidance spells out what manufacturing and preclinical data is needed to make such early meetings useful, and what expedited programs, standards, and support is available to researchers seeking to test new treatments (https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM623293.pdf).

A broader agency reorganization plan announced by Gottlieb in July aims to better coordinate advice and oversight for orphan drugs by establishing an Office of Clinical Policy and Programs (OCPP) that supports cross-cutting clinical programs involving multiple FDA medical product centers. Under the new structure, OCPP will report to FDA Deputy Commissioner Rachel Sherman and include the Office of Orphan Products Development (OOPD), the Office of Pediatric Therapeutics, the Office of Combination Products, and a new Office of Clinical Policy. OCPP also will oversee an expanded agency-wide program for patient affairs and healthcare providers to enhance engagement with these external stakeholders.

FDA officials plan to expand OOPD’s staff and programs under Janet Maynard, newly named acting director of the office. And FDA’s new orphan product council is meeting regularly and assisting in the development of additional guidance documents, reported Sherman at the NORD summit.

These initiatives stop short of establishing a separate FDA center of excellence for rare diseases, as sought by patient advocates in this area. But the planned organizational changes will mean that the oversight of new therapies for rare diseases, said Sherman, “will never become orphans” at FDA.


Jill Wechsler is the Washington Correspondent for Applied Clinical Trials


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