Bridging the gap: Tackling inequities in access to cystic fibrosis therapies

Cystic fibrosis (CF), an autosomal recessive disease, continues to cause premature mortality with a current life expectancy of 56 years. A perspective piece published in the Medical Journal of Australia (MJA) last week sheds light on the evolving therapeutic landscape and the pressing need for equitable access to innovative treatments.

The past century has seen significant progress in managing CF, marked by the 2011 introduction of the first disease-modifying therapy, Vertex’s Kalydeco (ivacaftor), 22 years after the CFTR gene was identified. The latest milestone is the triple-combination therapy comprising elexacaftor, tezacaftor, and ivacaftor (ETI) which is approved for people with cystic fibrosis with at least one F508del-CFTR allele.

“Given the rapidly evolving landscape of precision medicine, the Australian health technology assessment (HTA) pathway is undergoing its first review in over three decades. We eagerly await the outcomes and hope that new pathways will address current inequities in Australian cystic fibrosis patients’ access to disease-modifying treatments,” said lead author Professor Adam Jaffe, Paediatric Respiratory Physician at Sydney Children’s Hospital Randwick.

In Australia, approximately one-third of people with CF can access one of three modulator therapies. However, a significant portion remains excluded due to various factors, including age, unresponsive or extremely rare CFTR variants, or the lack of approval for certain therapies by the Therapeutic Goods Administration (TGA) despite U.S. FDA endorsement.

The limitations of traditional clinical trials further complicate the therapeutic landscape. Double-blind, placebo-controlled studies often rely on frequentist statistics to evaluate treatment effects at a group level. However, research by Boyle and colleagues has revealed variability in individual responses among patients with the same CFTR genotype. These findings, supported by subsequent trials of ETI underscore the need for predictive tools to personalise treatment and maximise individual outcomes.

To address these challenges, the authors advocate for the adoption of in vitro cell models as companion diagnostics. Primary cell organoids, for instance, could identify non-responders, preventing the administration of ineffective therapies and reducing low-value healthcare practices.

Additionally, n = 1 trials, which use patients as their own controls, offer a promising approach for evaluating treatments for rare CFTR variants. These innovative trial designs, often guided by Bayesian statistical methods, have already gained traction with the FDA for assessing therapies for rare diseases.

“Incorporating in vitro cell models into cystic fibrosis care could identify the best therapy (in terms of CFTR rescue) for patients with multiple therapeutic options and help address inequity by providing access for patients with rare variants,” the authors concluded.

In reimagining healthcare across the entire patient journey, Health Industry Hub^TM is the only one-stop-hub uniting the diversity of the Pharma, MedTech, Diagnostics & Biotech sectors to inspire meaningful change.

The Health Industry Hub^TM content is copyright protected. Access is available under individual user licenses. Please click here to subscribe and visit T&Cs here.