Thursday, May 5, 2016

First disease-modifying treatment should be approved for Duchenne

By: Michael Staley

Twelve young men in America hope to celebrate the five-year anniversary of their participation in a clinical trial for a drug called Eteplirsen on July 18th. They also hope that, by then, over 1000 other patients—or about 13 percent of the entire Duchenne Muscular Dystrophy population—will get a green light from the U.S. Food and Drug Administration (FDA) to begin receiving treatments as soon as enough of the drug can be manufactured.

Patiently waiting in the background are thousands of Duchenne patients who have most of their short-term hope invested in the underlying technology called exon skipping. Basically, the same technology used to develop Eteplirsen can be tweaked slightly to help different subsets of Duchenne patients.

Duchenne Muscular Dystrophy is a terrible genetic condition that leads to a complete loss of mobility and premature death. Complications from the associated cardiac and respiratory muscle weakness steal life from children as young as ten years old. Eteplirsen is designed to stop the progression of the condition by inducing the production of a vital protein—called dystrophin—that helps worked muscles recover.

In a 2015 interview, Scott Griffin of Birmingham candidly described the nightmarish reality his son Gabe will face without access to a drug to slow the progression of Gabe’s form of Duchenne.

  “But my son is going to have tubes coming in and out all part of his body, with a steel rod shoved in his back, his Achilles heel cords cut, not being able to roll over, not being able to lift his head up. I don’t think it gets much worse than that.”1

Scott Griffin holds his son, Gabe, in Iowa on July 19, 2014 during Ride4Gabe. (

In the late 1980’s, President Ronald Reagan spoke eloquently about how first generation treatments for AIDS could slow the progression of the condition until scientific doors could be opened for the development of more advanced and more effective treatments in the future.

  “It makes no sense, and in fact it’s cruel, to keep the hope of new drugs from dying patients. And I don’t blame those who are out marching and protesting…I sympathize with them, and we’ll supply help and hope as quickly as we can.”

  “Science is clearly capable of breathtaking advances, but it’s not capable of miracles…tests require time, and this is a problem money cannot overcome. We will not have a vaccine on the market until the mid-to late 1990’s, at best. Since we don’t have a cure for the disease and we don’t have a vaccine against it, the question is how do we deal with it in the meantime.”2

Announcing the first therapeutic agent for AIDS patients in 1986, Department of Health and Human Services Assistant Secretary Robert E. Windom called the results of the tests on the drug AZT “exciting” and said AZT was “the first therapeutic agent that seems to hold some promise for some AIDS patients.” According to The Washington Post, he also cautioned that the drug was not a cure and noted that, while promising tests triggered the release of the drug, it was still possible that the positive results would not persist and that unexpected side effects could appear.3

Dr. Janet Woodcock is the current FDA Director of the Center for Drug Evaluation and Research. Fortunately for Duchenne patients, Dr. Woodcock is well aware of the promise and hope found in the words President Reagan and Assistant Secretary Windom spoke about HIV/AIDS in the 1980’s.

In a 2012 hearing before the U.S. House Committee on Energy and Commerce, Dr. Woodcock reminded the committee of the important role the government played enabling doctors to transform AIDS from what was essentially a 10 year death sentence to a condition that people can live long and full lives with if managed properly.

   “I have had several people who are involved in the AIDS epidemic say to me if we had treated that as business as usual, we would never have solved this epidemic, we would have never gotten effective drugs available.”4

The FDA sometimes convenes advisory committees to collect independent expert advice on a range of complex scientific, technical, and policy issues. The FDA appoints experts who have “experience interpreting complex data” and are “able to analyze detailed scientific data and understand its public health significance.”5

Inside a Maryland convention center on April 25—about twenty miles outside of Washington, D.C.—a nearly twelve-hour public meeting of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee was held to evaluate Eteplirsen.6 As expected, the panelists spent most of their time debating the design of the Eteplirsen trials and whether 1 percent of a vital protein is better than none.

Above: April 25, 2016 FDA  Peripheral and Central Nervous Systems Drugs Advisory Committee (Photo Credit: Parent Project Muscular Dystrophy)

Then a series of things happened that are not “business as usual.”

First, Duchenne patients—including most of the Eteplirsen trial participants—took to the microphone during the Open Public Hearing portion of the meeting to provide their own expert testimony about how the drug is working for them. Patients described decreases in or absence of spontaneous falls. Others talked about being able to walk again after recovering from lower limb fractures attributable to brittle bones caused by heavy doses of steroids they are prescribed as Duchenne patients. Others noted a decrease, stabilization or smaller increase than would be expected in the use of mobility devices like wheelchairs or scooters. Finally, several even disclosed their increased ability to participate in activities of daily living such as using the restroom independently or getting in and out of bed. They presented all of this information to the FDA in a first-of-its-kind Patient Centered Outcomes Report detailing patient and caregiver outcomes of those enrolled in clinical trials of Eteplirsen.7

Next, Congressman Mike Fitzpatrick from Pennsylvania read a letter signed by 108 of his colleagues in the U.S. House of Representatives. The letter reminded the Advisory Committee members that Congress has a clear view about how the agency should apply the Accelerated Approval standard and flexibilities in the law to rare conditions like Duchenne.

  “FDA has been successful at applying flexibility in oncology and HIV/AIDS to speed patient access to apparently safe treatments, and the need and opportunity to adopt innovative and flexible approaches to the review of rare disease drugs has never been greater than it is today. Patients are waiting.” Mr. Fitzpatrick’s letter also notes that “it is critical the FDA take into account the views and experiences of patients as part of the review process. It is our understanding that the community worked collaboratively with regulators and benefit-risk experts to ascertain quantifiable patient-preference data…We urge the FDA to consider…the testimony and experiences of…patient representatives on the advisory committee and patients and expert clinicians who treat them as they testify during the open public hearing portion of the upcoming advisory committee.” 8

The FDA is considering Eteplirsen approval under its Accelerated Approval pathway for serious and life-threatening conditions. To be approved, the drug needs to demonstrate a “meaningful advantage over available therapies” and “demonstrate an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.”9

The predominant media message following the Advisory Committee Meeting focused on the fact that the panel delivered a split recommendation to the FDA—one favoring non-approval. One panelist who voted negatively noted his confusion in the record. Dr. Bruce I. Ovbiagele, chairman of neurology at the Medical University of South Carolina, said “Based on all I heard, the drug definitely works, but the question was framed differently.”

Dr. Janet Woodcock summed things up nicely in her comments during the Advisory Committee meeting on Eteplirsen. She said there is “an inherent presumption” under accelerated approval that “more uncertainty is going to be tolerated, at least at the beginning.” She also said that “Often there is never consideration of another error—that of not approving a drug that works.” 10

Duchenne Muscular Dystrophy is not “business as usual.” Anyone interested in advancing promising therapies to terminally ill patients with rare conditions should be focused on the FDA this month. If you are so inclined to reach out to the FDA with your own comments, you should encourage Dr. Woodcock to open the floodgates on Duchenne and approve the first disease-modifying treatment without further delay.

Michael Staley is a Senior Policy Advisor at Waller Landsen Dortch & Davis. He served as chief of staff to former U.S. Representative Spencer Bachus from 2007-2014. Michael advises clients on a range of issues including federal drug approval policy. He is active on the board of the Birmingham-based Hope for Gabe Foundation and an avid cyclist. For more information about Ride4Gabe, go to











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