July 2, 2018
In the coming weeks, CDER will publish online a list of surrogate endpoints that led to the approval of oncology drugs and biologicals, FDA Commissioner Scott Gottlieb announced at the National Comprehensive Cancer Network Policy Summit in Washington, D.C. “We believe this list will help to address some of the questions that have been raised about how we apply surrogates to make a given regulatory decision,” he said. “We’ll also be taking steps to provide more guidance to drug developers on these novel approaches.” The guidance will include how to design clinical trials that are based on a biomarker as a novel surrogate endpoint, and the agency will accept sponsor requests for Type C meetings earlier in the drug development process. The meetings can be requested to discuss using a biomarker as a surrogate endpoint in contexts where the marker was never the driving force behind approval. The efforts will give innovators and researchers more clarity about how the agency uses endpoints — and how it expects developers to evaluate biomarkers as surrogate endpoints — in a given disease state, Gottlieb said.
Report Says New Development Innovations Positively Impact Drug Success Factors
A report conducted by the Economist Intelligence Unit (EIU) found that new innovations in drug development positively impact drug development and market access, although the innovations are not yet widely adopted. The report, which was commissioned by PAREXEL, found that the new innovations showed a “surprisingly low” rate of adoption but positively affected drug success factors like clinical trial timelines, the probability of market launch and inclusion on selected payer formularies. After assessing clinical trial data and other sources in the U.S., EU, China and Japan, the report discovered that likelihood of launch was 10 percent higher for drugs developed with precision medicine trials, 13 percent higher for adaptive trials, 19 percent higher for patient-centric trials and 21 percent higher for trials that used real-world data.Neurologic, oncologic and rare disease drugs that used the innovations in their development experienced the most impact. Oncology drugs saw the most benefit with a 33 percent higher probability of launch.
CBER Launches Program to Meet With Sponsors to Advance Early Product Development
In an effort to provide advice to potential sponsors on critical topics for early drug development, CBER launched its Initial Targeted Engagement for Regulatory Advice on CBER Products (INTERACT) meetings program. INTERACT meetings replace the pre-pre-IND meeting process for all products across CBER. However, they do not replace formal meetings for specific products like pre-IND meetings or pre-BLA meetings that occur in later parts of development.Questions asked during INTERACT meetings should focus on topics related or similar to preclinical testing requirements, aspects of manufacturing required for first-in-human trials, device or assay design considerations and initial clinical development strategies.The advice given by CBER staff to a potential sponsor during an INTERACT meeting could help to streamline the product’s development process. For example, advice provided could help sponsors avoid unneeded clinical studies. The discussions can help to “answer important questions, remove roadblocks and, ultimately, help create a clearer route” toward developing safe and effective products for patients, the center said. CBER plans to post a revised web page describing the meeting program in greater detail in the coming months.
Cel-Sci Wins $3 Million in Arbitration From CRO That Underfilled Phase III Trials
A contract research organization must pay $3 million to Cel-Sci Corp. for underfilling a clinical trial for the drugmaker’s head and neck cancer candidate Multikine (leukocyte interleukin). In its arbitration suit, Cel-Sci claimed inVentiv — now known as Syneos Health — breached its contract with the drugmaker with false enrollment projections. The CRO enrolled fewer than 100 patients during its contract with Cel-Sci, and the drugmaker replaced it in March 2013 with two other CROs, Ergomed and ICON. Under the new CROs, the company successfully enrolled 928 patients in the Phase III study. The arbitrator found material breaches of contract. “We have been vindicated,” Cel-Sci CEO Geert Kersten said in a statement on the ruling, noting the CRO’s actions slowed down the clinical development of the immunotherapy. “The delays in the study caused by inVentiv not only delayed the potential approval of this investigational cancer drug by years, but it caused investors to wonder about the utility of the drug,” Kersten said.
Researchers Find That Compassionate Use Programs Benefit from Clinical Data Right-to-Try May Abridge
The recently-passed Right-to-Try legislation may upset the current balance between investigational new drug access and protection of patients in the FDA’s compassionate use programs, according to research published in JAMA Network Open. The researchers at Yale and New York University’s medical school examined data on two decades of compassionate use and expanded access for 92 experimental drugs that went on to secure FDA approval. They found that two-thirds of compassionate use programs gave patients access to experimental treatments just before the drugmakers submitted new drug applications when far more safety and efficacy data are available than at earlier stages. In the wake of the passage of the national Right-To-Try bill, the situation may change, as the legislation allows companies to let patients try experimental therapies without the FDA’s input. The change may have implications for safety and efficacy, the researchers said, because such data is typically not available by the point in the process at which the new law allows drugmakers to give experimental drugs to patients. “For medicines that ultimately receive FDA approval, these findings suggest that the FDA and the pharmaceutical industry have established a balance between investigational new drug access and protection of patients from therapies without established safety,” the researchers wrote. “This balance may be compromised by policy makers seeking to speed access to investigational medicines through the Right-to-Try Act.” Read the study abstract here: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2684626.
Cancer Trials Lack Social Factor Considerations, Johns Hopkins Scientists Say
Social factors like race, ethnicity and economic status should be more regularly taken into account when studying breast cancer risk and treatment outcomes, scientists at the Johns Hopkins Bloomberg School of Public Health say. For example, a 2014 review spanning over 20 years of NCI clinical trials showed that only about 20 percent of the randomized controlled studies stratified results by race or ethnicity. Follow-up analyses of 57 breast cancer observational and randomized controlled trials published in 2016 found that, after excluding trials that focused on disparities, fewer than five percent of them had findings stratified by race or other socioeconomic factors. Commentary by the scientists, which appears in the July edition of the medical journal Cancer Causes & Control, cited evidence that social factors help to determine patient vulnerability to cancer. They argue that the factors should be regularly looked at in studies and clinical risk assessments related to clinical care. “We’ve been missing opportunities to understand and reduce disparities in breast cancer risk and outcomes,” said lead author Lorraine T. Dean, an assistant professor in the Department of Epidemiology at the Bloomberg School. “Simply put, not enough is being done to understand how race, income level and other social factors tie in to cancer susceptibility.”
Synteract Partners With iCAN on Pediatric Research
Synteract announced a collaboration with the International Children’s Advisory Network (iCAN) that will enable the CRO to broaden its access to children and families familiar with clinical research. The network of children’s advisory groups works to give children and parents more input into research, medicine and innovation through education about the role of children’s involvement. Synteract has worked with pediatric clinical trials for the past 30 years and recently named pediatric drug development as one of its primary therapeutic centers of development. “By partnering with iCAN, we gain access to its wide network of children and families spanning socioeconomic, cultural and geographic backgrounds, which will be beneficial for the development of medicines for children,” said Martine Dehlinger-Kremer, Synteract’s head of pediatric development, said in a statement. “Our partnership with iCAN will be valuable in developing better, more appropriate protocols, study designs, patient facing documents and setting strategy for recruitment. It will also help us to further innovation in systems and treatments. It is another important step to show our commitment to this important population.”