'Burdensome' FDA Drug Approval Process Fuels Innovation, Saves Lives

David Kroll, Contributor

Source: Forbes.com

https://www.forbes.com/sites/davidkroll/2017/02/28/burdensome-fda-drug-approval-process-fuels-drives-innovation-saves-lives/#1a49e34176e0

I watched two speeches today that shared a common drug topic but with opposing philosophies. First, I saw former FDA director Rob Califf reflect on his recently-ended tenure at the agency while speaking to the Council for Entrepreneurial Development (CED) in Raleigh, NC. Then, like many of you, I watched President Trump's address this evening to a joint session of Congress.

The two men couldn't differ more in their views on how drugs and medical devices are developed in the United States.

Califf, a cardiologist, caught my attention today by saying, "Drug regulation drives innovation." He elaborated that the hurdles a new U.S. drug must meet in terms of safety and efficacy forces pharmaceutical companies to bring more first-in-class drugs or significant improvements over existing therapies to market.

Califf also noted that our major milestones in the progression of the drug development and approval process usually followed some catastrophic drug safety problem, such as the birth defects caused by thalidomide.

In contrast, President Trump has been extending his disdain for industry regulation to drug development, arguing tonight that, "We must eliminate the burdensome approval process for lifesaving drugs so that more lives can be saved."

During the president's speech, he acknowledged the attendance of Megan Crowley in the chamber, a 20-year-old woman stricken with a rare glycogen storage disorder called Pompe's disease that severely compromises neuromuscular functioning. The disease is due to the lack or a sub-optimal version of an enzyme that normally liberates stored glucose in glycogen to allow skeletal and cardiac muscle to contract and the liver and nervous system to function properly. Megan shares this autosomal recessive disease with her brother, Patrick. Pompe disease strikes only 50,000 people worldwide.

Following the childrens' Pompe's diagnosis in 1998, Megan's father, John Crowley, a former Bristol-Myers Squibb manager, decided to devote full-time effort to developing a treatment for his children. He co-founded Novazyme Pharmaceuticals and they developed an enzyme replacement therapy for Pompe disease, recombinant alpha-glucosidase (Lumizyme). Novazyme was acquired by Genzyme, the current marketer of Lumizyme for Pompe disease.

Crowley credits the enzyme therapy with keeping his children alive. The Crowley's story were the subject of two books and a movie, but it doesn't appear that FDA regulations slowed the development of Lumizyme. Instead, the agency requested proof of effectiveness and a safety profile that provided more benefits than risks.

During the drug trials, scientists learned that the enzyme therapy could cause life-threatening allergic reactions. Minimizing that condition, known as anaphylaxis, required that the drug be dosed more slowly, in stepwise increments every 30 minutes. The drug could also unexpectedly cause failure of heart or lung function. So patients must be followed closely during the intravenous drug administration.

Getting a handle on what was required to address safety problems took time. But what if the drugs were made available earlier, perhaps before the severe immune reactions were understood. Rather than celebrating the survival of his children, Crowley and Megan might not have been at the president's address this evening.

Another former FDA director, David Kessler, MD, spoke out tonight on Twitter, saying that the approval of Lumizyme was rather fast and accomplished with a minimal number of patients:

Califf similarly remarked on the careful balance the FDA must strike when considering a drug for approval. How long is long enough to adequately assure that a drug or medical device's effectiveness outweighs its safety concerns?

For this, Califf used the example of Sapien, a transcatheter replacement heart valve that was approved in Europe several years before the U.S. As a cardiologist, Califf admitted he was frustrated not to have access to the valve for his patients. But the delay in the approval time allowed clinicians to become better versed in minimizing risks from implantation of the valve. As a result, adverse reaction rates ran two-to-three times higher in Europe than in the U.S.

The FDA has made many advances in getting drugs to market more quickly, particularly with accelerated approval of cancer drugs, special incentives for antibiotic development and the extended access program for use of experimental drugs outside of a clinical trial. But relaxing the stringency of the drug approval process isn't the answer to treating patients more effectively.

David Kroll, PhD, is a former academic pharmacologist and medical educator. For more health and pharmaceutical news and commentary, follow Dr. Kroll on Twitter @DavidKroll.