It’s time to build the infrastructure needed to scale up inhaled gene therapies targeting cystic fibrosis, and to bolster investment that supports several key program components.

By JOAN LAU
Thanks to simultaneous achievements in gene therapy and medicine delivery platforms, new solutions to intractable problems are bringing us to a real watershed moment in the treatment of respiratory disease. This synchronicity of science and tech advancements is no accident; along with colleagues in my own and other organizations, I have been working for the past several years on the medical and technological leaps that together signal hope for respiratory-disease patients with unmet need.
This is especially true for those with cystic fibrosis (CF), for whom the standard of care is in urgent need of update. And now that we have the science and the technology in place, we must push to scale-up efforts; patients are waiting.

Right now, CF patients rely on treatments aimed at symptoms, not causes, such as antibiotics, anti-inflammatory medications, bronchodilators, and mucus thinners. While aggressive research has been conducted to improve treatments, 10% of CF patients remain non-responsive to the current standard of care due to their specific genetic mutations.

For patients experiencing advanced lung disease and respiratory failure, the extreme step of lung transplant surgery may be required. But now, the development of novel genetic therapies that address CF’s underlying genetic cause have the potential to reverse organ damage – and provide new hope for those with advanced disease who do not respond to or tolerate approved therapies.

One study calls CF “the Holy Grail for lung gene therapy.” Unlike other lung disorders that have complex causes and involve the interaction of multiple genes and contributing environmental factors, CF is a monogenic disorder, making it an ideal candidate for treatment via gene therapy. CF is also a progressive disease that limits life expectancy, and for which there is currently no cure. As such, the advancement of gene therapy poses a promising treatment option, and meets the need for delivery by inhaler – which gets treatment directly to the most severely affected organ, the lungs.

CFTR modulators may be able to restore function of faulty CF transmembrane conductance regulator (CFTR) proteins — that plays a role in creating sweat, mucus, tears, saliva and digestive enzymes — and improve lung function. Here is where gene therapies have tremendous potential to treat underlying causes of CF, genetic mutations that affect the CFTR gene, by delivering a new, correct version of the faulty CFTR gene into a patient’s cells. The faulty, mutated CFTR genes would still be present in the body, but the correct CFTR copies give the cells the ability to make normal CFTR proteins. In many cases, people receiving the gene therapy see their symptoms lessened and their condition improved, and coupling gene therapy with delivery by inhaler is opening the door to a new method of treating this debilitating disease.

Companies in the space, like mine, are making advances that combine effective gene therapy with delivery by inhaler or nebulizer. 4D Molecular Therapeutics recently announced early data that showed the effectiveness and safety of their gene therapy delivered via inhaler, which improved or stabilized lung function in three patients in a Phase 1/2 clinical trial, enabled gains in quality of life, and resulted in CFTR protein production. The demonstrated effectiveness of gene therapy for CF delivered by inhaler is leading to growing validation of the approach; in September, the UK Respiratory Gene Therapy Consortium announced the spin out of AlveoGene, a new gene therapy company that will employ gene therapy-delivery via nebulizer for direct, long-lasting impacts.

Given this promise and enthusiasm, it’s time to build the infrastructure needed to scale-up inhaled gene therapies targeting CF, and to bolster investment that supports a number of key program components. To accelerate new options, infrastructure supporting dose range finding studies or toxicology studies are needed – and that means labs capable of producing research-grade drug candidate screening preparations and larger material amounts at a quantity and quality suitable for non-GLP and GLP studies.

My colleagues and I have learned that building a viral vector core and end-to-end process development lab enables platform processes to be built with an eye on late stage demands while supplying nonclinical and clinical studies with consistent, high-quality material early on, decreasing the need for comparability studies later during drug development. These efficiencies are important to ensuring the development speed, safety and quality of potential treatments.

Just three decades ago, the average life expectancy of a person living with CF was about 30 years. While that has increased by 20 years, CF patients still face tremendous challenges. CF doesn’t just impact a person’s health, it curtails quality of life, making it impossible to see loved ones because of the risk of getting a virus that could be life-threatening or missing out on life events because of long hospital stays. Considering the promise shown in early data – and the ability of the inhaler to deliver effective gene therapy to where it’s needed, investment in inhaled gene therapy isn’t just likely to result in return on investment, it’s also the right thing to do. Patients are waiting; the time to push forward is now.

Photo from Flickr user NIH Image Gallery