Briefs

FDA Recommends Early, Pre-Approval Trials in Pediatrics for Systemic Dermatitis Drugs

April 16, 2018

The FDA published a new draft guidance outlining how early Sponsors should incorporate pediatric patients, and relevant age groups, for systemic therapies for atopic dermatitis (AD). The agency previously recommended that Sponsors submit pre-approval data on the use of topical products, but did not recommend pediatric studies of systemic drugs until after adult approval. The new draft guidance recommends Sponsors initiate pediatric studies early in development, typically after obtaining initial evidence from early-phase adult studies. In addition, Sponsors should discuss the specifics of their pediatric programs with the FDA as early as possible, as pediatric study plans are required to be submitted within 60 days after an end-of-Phase II meeting. The FDA said it is important to study all relevant age groups, including children younger than two years of age. A sequential approach may not be needed, except for safety concerns, technical issues or the need for information from older subpopulations to inform further study designs. Juvenile animal toxicity studies should also be considered before enrolling human participants. If approved, Sponsors should provide as much information as possible when labeling in regard to pediatric use. The agency said it is also planning a separate guidance to address the technical aspects of drug development for pediatric patients with AD. The draft guidance is available here: www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm603702.pdf.

FDA Outlines Considerations for Enrolling Pregnant Women in Clinical Trials

April 9, 2018

The FDA published a new draft guidance on the scientific and ethical considerations for including pregnant women in clinical trials, telling sponsors that data are needed to inform safe and effective treatment during pregnancy, and that it is appropriate to enroll pregnant women in certain situations. The agency said it considers it ethically justifiable to include pregnant women in clinical trials when adequate nonclinical studies have been completed, and when the trial holds the prospect of direct benefit to the women and/or the fetus that cannot be obtained by any other means. In the postmarket setting, an established safety database in nonpregnant women should be available, and inclusion should be allowed when efficacy cannot be extrapolated or safety cannot be assessed through other study methods.

Veeva and Six CROs Form New Industry Data Standards Group

April 2, 2018

Veeva Systems and six large contract research organizations formed a new technology standards group focused on improving trial collaboration with sponsors. The group — dubbed Align Clinical CRO — includes ICON, Medpace, Pharmaceutical Product Development, PRA Health Sciences, Syneos Health and UBC. “There is tremendous potential to enhance clinical trial execution with common technology standards that benefit the entire industry,” said Henry Levy, president of Align Clinical CRO, which aims to reduce operational costs and run trials faster. “By creating a vehicle for CROs to collaborate and share actionable insight with sponsors, we can improve operational delivery and streamline the increasingly complex trial process,” said Syneos Health CIO Rachel Stahler. The group expects to first deliver a pre-competitive operational data exchange standard, to facilitate information sharing between sponsors and CROs, including definitions related to trial operations, key metrics and milestones. The standard will be posted for public review and input before adoption, the group said. “This is the first time CROs are coming together to make this commitment to transform clinical trials across our industry, and we are excited to be part of this effort,” said Michael Brooks, executive vice president of product registration at PRA Health Sciences. “This shows our mutual commitment to make the drug development process more efficient and to help bring needed therapies to market more quickly.”

House Republicans Pass Right-to-Try Bill

March 26, 2018

The House passed its version of federal right-to-try legislation, sending it for reconsideration by the Senate, which passed a similar bill last August. The bill, H.R. 5247, had failed to garner enough votes on the floor last week to fast-track the bill under suspension of the House rules. Republicans that favor the legislation said they believe terminally ill patients, that have exhausted all other treatment options, should be able to try unproven therapies as a last resort. “For those patients caught between the traditional drug approval delays, a clinical trial process for which they do not qualify, and limited time, this right-to-try establishes the freedom for patients to try therapies in situations where the benefits far outweigh the risks,” said bill sponsor Rep. Brian Fitzpatrick (R-Pa.). Most Democrats opposed the bill, arguing that it would hinder the FDA’s oversight of investigational treatments — and contending that patients already have a program through which they can request access to experimental treatments. In addition, four former FDA commissioners — Robert Califf, Margaret Hamburg, Mark McClellan and Andrew von Eschenbach — as well as over 80 patient advocacy organizations opposed the bill because it would remove agency protections from the process.

IBM Watson Helps Increase Cancer Trial Enrollment

March 19, 2018

In the span of nearly a year, Mayo Clinic’s use of IBM’s Watson computing system for matching patients to clinical trials helped increase enrollment by an average of 80 percent in studies of systemic therapies for breast cancer. Over 11 months, the time needed to screen an individual patient for clinical trial matches also fell when compared to traditional manual methods, they said in a joint press release. In July 2016, Mayo began using the system with a team of screening clinical research coordinators in its ambulatory practice for patients with breast cancer. “This has enabled all patients to be screened for all available clinical trial opportunities,” said Mayo oncologist Tufia Haddad, physician leader for the Watson matching project. The two organizations also plan to expand training and use of the system, including using Watson in additional cancer types, as well as other aspects of cancer therapy, such as surgery, radiation and supportive care. Currently, the system is trained to support clinical trial matching for breast, lung and gastrointestinal cancers.

EMA Revises Guidance on Biomarkers for Alzheimer’s Therapies

March 12, 2018

The EMA’s Committee for Medicinal Products for Human Use revised its guideline on the clinical investigation of treatments for Alzheimer’s disease, focusing on the design and analysis of safety studies and the potential use of biomarkers in various stages of development. The revision, which takes effect on September 1, separates biomarkers according to their potential use: diagnostic, enrichment, prognostic, predictive and pharmacodynamic. The guideline notes that while most biomarkers still require validation for these purposes, cerebrospinal fluid markers, as well as MRI and PET imaging markers, “are qualified for the enrichment of study populations,” even though the biomarkers have not been qualified for use in preclinical Alzheimer’s disease. Identified adverse events should be categorized in relation to the treatment duration, applied dosage, recovery time, different age groups and other variables, the guideline said, and all adverse events occurring during clinical trials should be fully documented with a separate analysis of adverse drug events that lead to drop-outs and fatal outcomes. The revised guideline is available here: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2018/02/WC500244609.pdf.

NIH RA, Lupus Research Program Releases Cellular Datasets to Industry

March 5, 2018

An NIH research collaboration of rheumatoid arthritis and systemic lupus erythematosus has made its datasets, which characterize disease cells, available to the public. The program hopes researchers mine the data to accelerate the development of products and explore potential targets for new treatment options. The Phase I study, part of the Accelerating Medicines Partnership, analyzed individual cells from the lining of joints affected by rheumatoid arthritis and from kidneys damaged from lupus, hoping to better understand the specific pathways at play, and help to provide a new approach to understanding autoimmunity. The data also has potential implications for precision medicine, the NIH said. The program is one of three launched in 2014 as part of a public-private partnership, led by the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases, in cooperation with the National Institute of Allergy and Infectious Diseases. Investigators are currently conducting Phase II studies, including larger cohorts of patients. The Foundation for the NIH manages the partnership with industry, including AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Sanofi and Takeda Pharmaceuticals, as well as nonprofits such as the Arthritis Foundation, Lupus Foundation of America, Lupus Research Alliance and Rheumatology Research Foundation. The Phase I data are freely available through the NIAID-sponsored Immunology Database and Analysis Portal, at www.immport.org. Genomic data are also being submitted to be made available through the NIH’s database of Genotypes and Phenotypes, at: www.ncbi.nlm.nih.gov/gap.

NHGRI Launches Strategic Planning Process for Genomic Research and Funding

February 26, 2018

The National Human Genome Research Institute has begun to refocus its research and funding strategies with new emphasis on the development of precision medicines, exploring the basis for certain diseases and supporting the industry’s education in data science. The main federal institute behind the Human Genome Project, NHGRI plans to prioritize its efforts in emerging areas, such as the use of genomic information in patient care and drug development, and plans to gather input from the industry and the public over the next two years. The NHGRI’s strategic plan is expected to be finalized in October 2020, which commemorates the Human Genome Project’s 30th anniversary. The institute expects to prioritize emerging areas that are not well-defined, that will benefit from significant investments and are not specific to particular diseases. Well-established areas, such as cancer and microbial genomics, are expected to be deemphasized during the upcoming process, the institute said.

FDA Releases Guidances on Clinical Trial Design for Neurological Treatments

February 19, 2018

The FDA has released five guidances on clinical trial designs and endpoints for developing treatments for a variety of neurological disorders, including Alzheimer’s disease, Duchenne muscular dystrophy (DMD) and ALS. The revised draft guidance on Alzheimer’s disease noted a greater focus on evaluating drug treatments during the disease’s earliest stages, partially due to the failures of clinical trials that aimed to alter later stage disease progression. Diagnostic criteria that reliably define an early Alzheimer’s population are suited for evaluating drugs that try to delay or prevent overt symptoms, the agency said. Enrollment eligibility for Alzheimer’s drug efficacy trials should be centered around current consensus diagnostic criteria, focusing on objective tests in addition to history and physical examination when appropriate, to determine the disease’s presence and rule out similar conditions. Alzheimer’s Stage 1 patients — who exhibit evidence of clinical impact — are important targets for clinical trials, although clinically meaningful benefits cannot be measured in them due to a lack of clinical impairment. However, effects on the characteristic pathophysiologic changes of AD — demonstrated by effects on biomarkers — may be measured in these patients, and the measurements may serve as the basis for an accelerated trial, as the biomarker effects would be “reasonably likely to predict clinical benefit,” with a post-approval study required for confirmation. The agency’s final guidance on DMD and related dystrophinopathies said endpoints measuring change of function in a wide range of deficits may offer advantages in the development of drugs that treat diseases like DMD and Becker muscular dystrophy, in addition to increasing the number of patients eligible for enrollment. Sponsors should consider using endpoints that are able to assess function across different stages of the disease — such as combining measures of upper body function and ambulation — and detect improvement and decline from baseline in order to capture the range of possible beneficial drug effects. Patient-reported outcomes (PRO) can be useful for assessing clinical meaningfulness of relatively small objective findings, and for contributing benefit and risk assessments. PRO instruments for dystrophinopathies should, in general, “include a limited number of items that assess the most important aspects of the outcome of interest.” The final guidance on drug development for acute treatment of migraines, which does not apply to over-the-counter products, elaborated on ideal trial design, trial population and entry criteria, dose selection, efficacy endpoints and concomitant medications, among other topics. Draft guidance issued on drugs for the treatment of partial onset seizures explained that “efficacy can be extrapolated from adults to pediatric patients when it is reasonable to assume that children, compared with adults, have a similar progression of disease, similar response of disease to treatment, and similar exposure-response relationship.” The draft guidance on developing drugs for ALS treatment addresses the clinical development of drugs intended to treat the main neuromuscular aspects of the disease and focuses on specific clinical drug development and trial design issues that are unique to the study of ALS. The guidances “signal how modernization of the new drug regulatory program includes an enhanced focus on incorporation of patient input into our thinking,” said FDA Commissioner Scott Gottlieb. Read the five guidances here: www.fdanews.com/02-15-18-Guidances.pdf.

EMA Draft ‘Strengthens’ Guidance on Safety Follow-Up for Advanced Therapies

February 12, 2018

The EMA published a draft revision to its guideline for clinical trials follow up of advanced therapy medicinal products, including gene therapies, cell therapies and tissue engineered products. The draft strengthens and clarifies the EMA’s 2008 guideline, and includes more details on designing post-authorization safety and efficacy follow-up studies. Sponsors need to provide safety and efficacy follow-up data in their marketing applications, including long-term data to analyze the benefits and risks of products. Objectives for safety follow-ups should be based the on specific product characteristics than on its classification, such as whether it is a cell- or gene-based therapy, or a combination. The evaluation of the long-term efficacy is a key issue for gene therapies as premarket clinical trials typically include a limited number of patients and with a limited duration. The EMA suggested sponsors provide long-term follow-up data in several situations, such as for cell therapies with a short shelf life, which may require monitoring of efficacy and the need for re-administration. Immunogenicity is also a critical consideration for the efficacy assessment of a cell-based product. The EMA’s draft guideline is available here: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2018/02/WC500242959.pdf.