In the JournalsPerspective

Novel study design, open dialogue on drug development critical to JIA drug pipeline

Yukiko Kimura

Opening dialogue between regulatory agencies, pharmaceutical companies and clinicians to develop and implement novel clinical trial designs could be one possible way to increase access to new medicines for patients with juvenile idiopathic arthritis, according to a commentary published in Arthritis & Rheumatology.

“There are unique challenges to bringing drugs to market for children that often delay or prevent treatments approved for adults with inflammatory arthritis from being available to the pediatric community,” Yukiko Kimura, MD, of the Hackensack Meridian School of Medicine at Seton Hall, and co-chair of CARRA Research and Registry Oversight, told Healio Rheumatology. “In addition, study designs routinely used in adult trials may not be acceptable to families and pediatric providers.”

“Placebo controlled clinical trials have been the gold standard for authorizing new medicines for the treatment of rheumatic diseases, but are no longer feasible in rare diseases such as JIA,” she added. “The numbers of new treatments for inflammatory arthritis have grown exponentially. Children and adolescents with inflammatory arthritis need access to these effective new treatments, so new approaches to authorizing these medicines for children are needed.”

To discuss and suggest possible routes toward expanding access to JIA treatments, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) hosted a 1-day meeting between pharmaceutical company officials, pediatric rheumatology clinicians, patient representatives, the FDA, the European Medicines Agency and the Arthritis Foundation.

 
Opening dialogue between regulatory agencies, pharmaceutical companies and clinicians may lead to increased access to new medicines for patients with JIA, according to a commentary.
Source: Adobe

The meeting, held on April 11, 2018, in Denver, saw the stakeholders discuss the current state of JIA clinical trials, outcome measures, the role of registries and potential new approaches.

According to the meeting participants, registration trial designs to test medicines among patients with JIA should adapt to changes in clinicians’ treatment repertoire regarding inflammatory arthritis. Methodologies that have been successful in the past are no longer useful, they added, as the pool of patients who meet the inclusion criteria, and are willing to participate, decreases. Meanwhile, the number of drugs that require trials continues to increase.

Possible solutions include collaboration among stakeholders, including regulatory agencies, pharmaceutical companies, with the goal of reducing barriers to regulatory approval. In addition, representatives from the FDA and European Medicines Agency discussed the use of novel clinical trial designs, including open-label and Bayesian methodologies.

“One major takeaway was the need for frequent and open dialogue between regulatory agencies and companies to plan the best pediatric drug development programs for each medication, including input from clinicians, researchers, patients and parents,” Kimura said. “In addition, stakeholders discussed different approaches to drug development, such as the use of real-world data and extrapolation from adult arthritis trials in order to make the approval of new medications faster and more efficient. Lastly, no matter how the authorization studies are conducted, the long-term safety of these medicines in children must be studied rigorously in a large disease specific registry that will follow patients for long periods.”

Kimura added that she hopes the meeting will eventually lead to changes at the FDA.

“The FDA is holding a public workshop on October 2, 2019, to discuss drug development for JIA, focusing on the feasibility of extrapolation from adult arthritis trials and other study approaches,” she said. “Hopefully, the workshop will lead to changes in FDA guidance that will help ensure that effective new treatments will be more rapidly available for children and adolescents with different forms of JIA.” – by Jason Laday

Disclosure: Kimura reports salary support from CARRA and a research grant from Genentech through CARRA. See the full study for additional authors’ disclosures.

Yukiko Kimura

Opening dialogue between regulatory agencies, pharmaceutical companies and clinicians to develop and implement novel clinical trial designs could be one possible way to increase access to new medicines for patients with juvenile idiopathic arthritis, according to a commentary published in Arthritis & Rheumatology.

“There are unique challenges to bringing drugs to market for children that often delay or prevent treatments approved for adults with inflammatory arthritis from being available to the pediatric community,” Yukiko Kimura, MD, of the Hackensack Meridian School of Medicine at Seton Hall, and co-chair of CARRA Research and Registry Oversight, told Healio Rheumatology. “In addition, study designs routinely used in adult trials may not be acceptable to families and pediatric providers.”

“Placebo controlled clinical trials have been the gold standard for authorizing new medicines for the treatment of rheumatic diseases, but are no longer feasible in rare diseases such as JIA,” she added. “The numbers of new treatments for inflammatory arthritis have grown exponentially. Children and adolescents with inflammatory arthritis need access to these effective new treatments, so new approaches to authorizing these medicines for children are needed.”

To discuss and suggest possible routes toward expanding access to JIA treatments, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) hosted a 1-day meeting between pharmaceutical company officials, pediatric rheumatology clinicians, patient representatives, the FDA, the European Medicines Agency and the Arthritis Foundation.

 
Opening dialogue between regulatory agencies, pharmaceutical companies and clinicians may lead to increased access to new medicines for patients with JIA, according to a commentary.
Source: Adobe

The meeting, held on April 11, 2018, in Denver, saw the stakeholders discuss the current state of JIA clinical trials, outcome measures, the role of registries and potential new approaches.

According to the meeting participants, registration trial designs to test medicines among patients with JIA should adapt to changes in clinicians’ treatment repertoire regarding inflammatory arthritis. Methodologies that have been successful in the past are no longer useful, they added, as the pool of patients who meet the inclusion criteria, and are willing to participate, decreases. Meanwhile, the number of drugs that require trials continues to increase.

Possible solutions include collaboration among stakeholders, including regulatory agencies, pharmaceutical companies, with the goal of reducing barriers to regulatory approval. In addition, representatives from the FDA and European Medicines Agency discussed the use of novel clinical trial designs, including open-label and Bayesian methodologies.

“One major takeaway was the need for frequent and open dialogue between regulatory agencies and companies to plan the best pediatric drug development programs for each medication, including input from clinicians, researchers, patients and parents,” Kimura said. “In addition, stakeholders discussed different approaches to drug development, such as the use of real-world data and extrapolation from adult arthritis trials in order to make the approval of new medications faster and more efficient. Lastly, no matter how the authorization studies are conducted, the long-term safety of these medicines in children must be studied rigorously in a large disease specific registry that will follow patients for long periods.”

Kimura added that she hopes the meeting will eventually lead to changes at the FDA.

“The FDA is holding a public workshop on October 2, 2019, to discuss drug development for JIA, focusing on the feasibility of extrapolation from adult arthritis trials and other study approaches,” she said. “Hopefully, the workshop will lead to changes in FDA guidance that will help ensure that effective new treatments will be more rapidly available for children and adolescents with different forms of JIA.” – by Jason Laday

Disclosure: Kimura reports salary support from CARRA and a research grant from Genentech through CARRA. See the full study for additional authors’ disclosures.

    Perspective
    Carolyn Zic

    Carolyn Zic

    The conclusions of this article may prove to be of great importance to both providers caring for children with JIA as well as to patients and families by providing some encouragement that changes may be on the horizon. The authors express the urgency for a need for change in the current research landscape, highlighting the necessity to progress care for children with JIA. These feeling are echoed in the community caring for pediatric patients with rheumatic conditions.

    We know that access to medications to effectively treat disease in a timely fashion is vital; however, there remains a drastic gap in access to treatments as there are limited FDA-approved medications available for patients with JIA.

    Stepping back to take a critical look at how clinical studies are conducted while maintaining the protection of the vulnerable subjects (pediatric patients) is a complex task. However, it is imperative to exam the current process and how that may be affecting the ability of new treatments in the pediatric rheumatology space.

    Allowing families and other patient advocates a ‘seat at the table’ in this review process assists in ensuring that patients’ needs are met and their voices are heard, paving the way for further advancements in research and access to new treatments. 

    • Carolyn Zic, RN, BSN, CPN
    • Pediatric rheumatology nurse
      Comer Children’s Hospital
      University of Chicago Medicine
      Board member, Rheumatology Nurses Society

    Disclosures: Zic reports no relevant financial disclosures.