Incentivized: Why Drug Development for Cystic Fibrosis has Fared Better Than the Current State of Antibiotic Creation

Cystic fibrosis (CF) patient advocate Gunnar Esiason is living in a world where advancements in CF therapy have greatly improved his quality of life, but he also remains concerned about a future respiratory infection that could be drug-resistant to all available antibiotics, and may have serious health consequences.

During his senior year of college, Esiason was struggling with a severe respiratory infection with the bacterium, Pseudomonas aeruginosa. Esiason was born with CF, and had been dealing with these types of infections periodical throughout his life. In fact, for people with CF, they are suspectable to this pathogen, as it will colonize inside the lungs.

And while Esiason fought the previous infections successfully with antibiotics, this particular bout felt different. His health, as he describes it, was in a “free fall.” He says it felt as if he was in end stage illness and his lungs were overwhelmed with Pseudomonas aeruginosa. During this period which lasted for years, he had many days where he experienced a variety of issues including reoccurring fevers, multiple antibiotic IV treatments, and fatigue so bad he could barely get up to brush his teeth.

Although he had many lows during this time, Esiason remained optimistic about the future of CF therapeutics. “Looking back at that time, I felt hope that there were medicines on the horizon that would treat the underlying cause of my cystic fibrosis,” he said.

Continuous drug development in this space has led to better therapies. With dedicated organizations like the Cystic Fibrosis Foundation and others advocating for better treatments, they had a voice to get things done.

That hope came to Esiason and other CF patients in the form of the combination therapy, elexacaftor/ivacaftor/tezacaftor (Trikafta), which was approved in October of 2019. The agent is the first triple combination therapy available to treat patients with the most common cystic fibrosis mutation, which represents 90% of the CF population, according to the FDA.¹ It has been called a miracle drug by some.

Just two generations ago, children diagnosed with CF were not expected to live into adulthood. Life expectancy for individuals with cystic fibrosis was 14 years back in the 1980s.²

For the youngest CF patients today, life expectancy has dramatically increased. “Based on the 2021 CF Foundation Patient Registry data, the current life expectancy for CF patients born between 2017 and 2021 is 53 years—a substantial jump from a decade ago when the life expectancy was 38. Now, almost 60% of us are older than 18,” the Cystic Fibrosis Foundation writes on its website.³

Still Esiason remains vigilant for the next bacterial infection he will contract. “We are grateful that CF is very much a manageable condition, but I know in the back of my mind, I have run my antibiotic list through to the end.”

So, there remains this dichotomy of ongoing, active drug development for a chronic condition such as CF, but there is this tremendous lag for creating new antimicrobials.

Incentivizing Pharma to Boost Antimicrobial Development
We are all dependent on antibiotics; we are just one multidrug resistant bacterial infection away from having serious complications including and leading up to death. However, most of us are able to put that to the back of our minds as we think of it as a theoretical threat, and not a reality. That might be the calculus for many people, but if you are dealing with a chronic illness that repeatedly could spur a new infection your concerns take on a different perspective.

The road to antibiotic development is a difficult one. From the creation of a new agent, and getting through the multiple trials, the whole process can 10-15 years on average to get a drug approved and to market.

One estimate looking at the total cost to develop an antimicrobial was $1.5 billion.⁴ And the rate of return for pharmaceutical companies can also make it difficult to get involved. One estimate done by industry analysts estimated the sales for an antibiotic is approximately $46 million annually.⁵

Even after development and getting an antibiotic through the approval process, drug resistance can happen within a couple of years.

And most significantly, large pharmaceutical companies have left the antimicrobial development space. It has been dominated by smaller or late-stage biopharmaceutical companies who may be reliant on the one particular investigational microbial they are trying to bring to market.

Understanding the nature of the dearth of antimicrobial development has spawned Congress to write a bill, named the Pioneering Antimicrobial Subscriptions to End Up surging Resistance (PASTEUR) Act. It’s named after Louis Pasteur, the famous French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation, and pasteurization.

The bill was initially introduced in Congress by US Senators Michael Bennet (D-Colo.) and Todd Young (R-Ind.) in September of 2020. Bennet and Young along with Representatives Mike Doyle (D-Pa.) and Drew Ferguson (R-Ga.) reintroduced the bill in June 2021. The Pasteur Act aims to incentivize innovative drug development targeting the most threatening infections, improve the appropriate use of antibiotics, and ensure domestic availability when needed.

“The Pasteur Act is all about incentives and disincentives that exist for drugmakers right now,” Esiason said. “The reason why we have these highly effective medicines that have been able to alter the course of cystic fibrosis is because drugmakers have been incentivized to go after CF.” He mentions the work of for-profits and non-profits partnering together as well as the importance of the Orphan Act in aiding the development of CF therapies.

He goes on to say the Pasteur Act looks to solve the economic disincentives that exist when it comes to antimicrobial development. 

CF patient advocate Gunnar Esiason

Today, Esiason is 31 years old, has a wife and young son, and so much more to do. He is the head of patient-facing strategy at Florence Healthcare and remains passionate about early-stage drug development, patient empowerment and health policy.

He holds an MBA from the Tuck School of Business at Dartmouth, where he was a Wilson Scholar and received the Julia Stell Award, and an MPH from the Dartmouth Institute for Health Policy & Clinical Practice.

Professionally, he has developed a patient engagement platform for a medical nutrition company, built a venture philanthropy practice at the Boomer Esiason Foundation, which has yielded more than $160 million raised for the fight against cystic fibrosis. And he was the head coach of his high school alma mater’s varsity hockey team.

He has consulted on clinical trial development, a real-world evidence population health study, and a cystic fibrosis-specific mental health and wellness screening tool. And his blog has amassed nearly 1 million page views since 2015. His podcast, the State of Health, is available on all streaming platforms.

His advocacy lends a voice to what clinicians, public health officials, and patients all know: something needs to change in terms of the paradigm of antimicrobial development.

An Understanding of Antimicrobial Development and Approvals
Currently some antimicrobials that are in development or approved for other indications may be studied to see if their agents can work against other pathogens.

For example, imipenem-cilastatin-relebactam (Recarbrio) was initially FDA approved in 2019 to treat intra-abdominal infections and complicated UTIs. The next year, the FDA approved its use for Hospital-Acquired Bacterial Pneumonia (HABP), and Ventilator-Associated Bacterial Pneumonia(VABP). This was granted under a Qualified Infectious Disease Program (QIDP) designation.⁶

Although the jury remains out on the efficaciousness of this therapy against Pseudomonas aeruginosa, the bacterium is one of the most frequent pathogens for these forms of pneumonia, and it is likely there will be more studies to determine if the therapy is effective against it.

Will the Pasteur Act Pass?
Although no news has come from the Capitol on the prospect of the bill passing, some in Washington believe it.

Amanda Jezek, senior vice president of public policy and government relations at IDSA, is optimistic that the legislation will be passed. In an interview at the ID Week conference this past October, she said the Pasteur Act had 65 bipartisan cosponsors in Congress. In addition, as part of trying to emphasize the bill, members of the IDSA Board members who were in Washington during the conference visited with Health and Human Services (HHS) Secretary Xavier Becerra as well as different members of Congress.

When talking to staff of republican and democratic congressional members there is a bipartisan appeal to the Pasteur Act according to Jezek. “Everywhere we go, people say, ‘yes we need action on [antimicrobial resistance] AMR,’” Jezek stated. “We are excited to keep building the momentum and get this bill across the finish line and send it to the President’s desk.”

Esiason is again turning to positivity in his belief in pharmaceutical companies. "I do have hope that our drugmakers can conquer and combat drug resistance with these troublesome infections that are emerging today because I’m proof positive of having a disease that has been altered by biochemistry.” 

References

1. FDA approves new breakthrough therapy for cystic fibrosis. News release. FDA. October 21, 2019. Accessed February 3, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-breakthrough-therapy-cystic-fibrosis

2. Cystic Fibrosis Life Expectancy Statistics. Disabled World. Updated June 11, 2013. Accessed February 3, 2023. https://www.disabled-world.com/health/respiratory/cystic-fibrosis/life-expectancy.php#:~:text=In%20the%201980s%20life%20expectancy,4%20years%20to%2032%20years

3. People With CF Are Living Longer. What Does That Mean for Our Care? Cystic Fibrosis Foundation. August 11, 2022. Access February 3, 2023. https://www.cff.org/community-posts/2022-08/people-cf-are-living-longer-what-does-mean-our-care#:~:text=Based%20on%20the%202021%20CF,us%20are%20older%20than%2018

4. Weiner LM, Webb AK, Limbago B, et al. Antimicrobial‐resistant pathogens associated with healthcare‐associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infect Control Hosp Epidemiol. 2016;11:1288‐1301

5. Why big pharma has abandoned antibiotics. Nature. October 21, 2020. Accessed February 3, 2023. https://www.nature.com/articles/d41586-020-02884-3#:~:text=A%202017%20estimate%20puts%20the,roughly%20%2446%20million%20per%20year.

6. FDA Approves Antibiotic to Treat Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia. News release. FDA. June 4, 2020. Accessed February 3, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-antibiotic-treat-hospital-acquired-bacterial-pneumonia-and-ventilator-associated