Positive Prognosis for The 21st Century Cures Act
By Michelle Hoffmann, PhD
After years of development, President Barack Obama has signed into law the 21st Century Cures Act, a $6.3 billion bill with the potential to change healthcare as we know it by moving drugs and devices more quickly to patients in direst need. Cures has given us a great deal to ponder– and to act upon – for the betterment of patients and to reenergize our diminishing position as a world leader in science.The new law bolsters scientific research and advances the regulatory process to spur product development and speed time to market for newer medications and medical devices. Cures:
Creates new programs for the development of regenerative medicine products, the next frontier of medicine.
Strengthens FDA and NIH capabilities and addresses the most pressing public health problems of our time, including cancer, opioid abuse, mental health issues and deadly brain disorders for which little progress has been made.
Serves as a healthy step toward eliminating ailments that have seen few breakthroughs and pose tremendous human and financial costs.
Controversy is in the eye of the beholder
Cures act provisions are controversial depending on views of the FDA as part of the regulatory red tape that holds back progress, or consumer and patient bulwark standing between us and the next disastrous drug, such as thalidomide.As with every significant change in regulations and incentives, especially one that has had myriad lobbyists and interests cobbling a bill together, perverse incentives can emerge.
But biotech-pharma proves repeatedly that unintended consequences can go both ways -- good and bad.For the patients’ sake, we encourage everyone to critically access legislation to reduce regulatory burden. But do so through a lens of differentiation: not all situations are comparable. For instance, it is imperative to expeditiously approve a treatment for patients at the critical point in their care when there are few options to draw from, Sarepta is one example but acts more judiciously where a myriad of treatments are available.
Studying stem cells and ‘regenerative medicine’ with surrogate markers
The 21st Century Cures Act will bring Regenerative Medicine into the mainstream and provide the FDA with accelerated approval authority. The specter of powerful donors linked to these regulations and early indication that accelerated authority would mean skipping over phase 111 studies – a critical step to access efficacy, efficacy and safety in humans – had many concerned.Skipping from animal models to market data would hasten time to marked for effective regenerative therapies, and possibly increase opportunities to hawk therapies that amount to modern “snake oil”, said some critics.
In fact, the majority regenerative medicine is advanced by responsible academia and industry and offer true medical advancement with regularity. Initial effort to do away with pivotal phase III testing is now gone, replaced with expedited approval, potentially on the basis of surrogate endpoints, a pathway that has been used many times before with success. For many of the sickest patients, the promise of regenerative medicine, stem cell therapy in particular, may be the final attempt at treatment and cure. Stem therapies may show improvements in surrogate measures, such as vascularization in a patient with Critical Limb Ischemia (CLI), but overall outcomes equivalent that are discouraging at best, “sham” at worst. Complex therapy given to critically ill patients which shows some efficacy signals but fails to improve gold standard measures of mortality and morbidity may not point to an ineffective drug. It can mean the compound is difficult to study. If the compound is brought market with guidance and caution, patients can receive the treatment earlier and potentially show clinical benefit in a way that may be difficult to achieve with clinical trials. Cures opens the door to these possibilities.
Label expansion via Real World Data is not simply wait and see
The 21st Century Cures Act allows the FDA to consider Real World Evidence when approving a label expansion. Again, critics fear this will allow drugs to be released with only Real World Experience, rather than rigorous clinical data, to determine quality and efficacy. Although the FDA has yet to provide a framework, this scenario provides the FDA with context to consider data signals from the massive amounts of patient data that exists in health care systems, especially with the implementation of Electronic Health Records.Yes, a full clinical submission for label expansion was how the public learned about the cardiotoxicity of Vioxx. But the cardiotoxicity was, in part, confirmed through Kaiser’s sophisticated reporting system that tracked patient doses and outcomes. If coupled with responsible marketing practices, this part of the Act might allow the application of Big Data to determine new uses for old drugs.
Small populations may be the right place to study the antimicrobials of last resort
Cures addresses the need for development of anti-infective and antifungal agents for patients with life-threatening infections where existing treatments have no clinical impact. Approvals will be shunted by data from limited population studies.Currently, antimicrobials are approved based on their application, such as uncomplicated urinary tract infections (uUTI). However, in the age of microbial resistance, patient populations with resistant bugs require antibiotics tested in a pathogen-specific way, similar to so-called basket trials in cancer research.The Cures Limited Population pathway means targeted, specific research for seriously ill patients and the FDA expects to label as such to assure narrow use in limited populations while the drugs are studied for broader use. This belies Cures critics who point to limited studies as a way to bring a product to the widest population as quickly as possible.
The 21st Century Cures Act is unwieldy, imperfect legislation to be sure. However, those of us immersed in the biotech-pharma sector see the potential for great strides forward and treatments brought to market more quickly. Medication and medical devices with the potential to address unmet medical needs for serious diseases can now more quickly make their way to the people who need them most. And that is a positive outcome for the industry, patients and scientific advancement overall.