• Hypertrophic Cardiomyopathy (HCM)
  • Vaccines: 2023 Year in Review
  • Eyecare
  • Urothelial Carcinoma
  • Women's Health
  • Hemophilia
  • Heart Failure
  • Vaccines
  • Neonatal Care
  • Type II Inflammation
  • Substance Use Disorder
  • Gene Therapy
  • Lung Cancer
  • Spinal Muscular Atrophy
  • HIV
  • Post-Acute Care
  • Liver Disease
  • Pulmonary Arterial Hypertension
  • Biologics
  • Asthma
  • Atrial Fibrillation
  • Type I Diabetes
  • RSV
  • COVID-19
  • Cardiovascular Diseases
  • Breast Cancer
  • Prescription Digital Therapeutics
  • Reproductive Health
  • The Improving Patient Access Podcast
  • Blood Cancer
  • Ulcerative Colitis
  • Respiratory Conditions
  • Multiple Sclerosis
  • Digital Health
  • Population Health
  • Sleep Disorders
  • Biosimilars
  • Plaque Psoriasis
  • Leukemia and Lymphoma
  • Oncology
  • Pediatrics
  • Urology
  • Obstetrics-Gynecology & Women's Health
  • Opioids
  • Solid Tumors
  • Autoimmune Diseases
  • Dermatology
  • Diabetes
  • Mental Health

Controversy surrounds Exondys 51 approval: What to know


New medicine for Duchenne muscular dystrophy raises questions. Here’s whose covering it and why.

Although only 22 novel drugs were approved in 2016-fewer than half the number the previous year, according to the FDA’s Center for Drug Evaluation and Research-one drug leaves a cloud of controversy behind it: Exondys 51 (eteplirsen) for Duchenne muscular dystrophy (DMD). The new medication, approved September 19, 2016, is for patients with a confirmed mutation of the dystrophin gene that is amenable to exon 51 skipping-13% of the population with DMD, according to the FDA.

Despite a recommendation against approval from an independent advisory committee of scientists, the FDA granted the drug an accelerated approval based on a surrogate endpoint-whether Exondys 51 could increase dystrophin, a protein promoting skeletal muscular movement.

The FDA determined that the application meets the requirements for accelerated approval based on the effect of the drug on the surrogate endpoint-increased dystrophin production in skeletal muscle observed in some eteplirsen-treated patients-which was concluded to be reasonably likely to predict clinical benefit. 

“In appropriate situations, the agency exercises flexibility when evaluating treatments for serious and life-threatening conditions,” says an FDA spokesperson.

The approval, however, comes with a provision-a follow-up trial from Sarepta Therapeutics, the drug’s manufacturer. It will be a two-year, randomized, double-blind controlled trial assessing motor function, in which two dose levels of eteplirsen-the approved dose of 30 mg/kg weekly and a significantly higher exposure-will be tested in patients with mutations amenable to exon 51 skipping. If the trial is unable to prove that clinical benefit, the FDA could withdraw approval.

Criticisms and concerns

The approval surprised many who claimed the research was flawed in studying just one genetic mutation in a small population of 12 boys. After three trials, the level of dystrophin in muscle biopsies improved by a median of only 0.1%, according to the FDA.


The trials for Exondys 51 worry Kaiser Permanente, says Sameer Awsare, MD, associate executive director, Permanente Medical Group, because of the small number of participants; however, he realizes that DMD is a rare disease only affecting a small population.

“We are not clear about the benefit of the drug,” he says, referring to the 0.1% increase in the amount of protein added to a patient’s system after taking the drug-the surrogate measure used to test the drug in trials.

In addition, the six-minute walk test used to determine how far a patient with DMD can walk in that timeframe-a key tool in the trials-did not indicate any significant clinical difference after taking the drug-a reason he says the FDA did not approve Exondys 51 at first.

“We are concerned when the FDA hesitates to approve a drug-whether the process could possibly be broken,” he says.

Next: Formulary or not?



On formulary or not, insurers decide

Health plans have weighed the evidence and among the largest insurers, all but Anthem have put the new drug on formulary, albeit with conditions.

In addition, Express Scripts, a pharmacy benefits manager based in St. Louis, decided not to include the drug on its national formularies based on the currently available research related to the safety and efficacy of the medication.

Randy Vogenberg, principal at the Institute for Integrated Healthcare, says that insurers made their decisions about coverage based on a few considerations.

“Some insurers are trying to slow down rare disease approvals and create better standards around acceptable data for coverage consideration; some have not addressed what to do in a controversial situation like the one surrounding this product at a time when tremendous economic pressure surrounds biologic and specialty drugs,” he says.

Kaiser’s approach

Kaiser Permanent put Exondys 51 on its national Part D formulary but not on its California drug list.

“We cover Exondys 51 when the drug is determined to be medically necessary by a member’s physician, as we do with all FDA-approved pharmaceuticals,” Awsare says. “We continually monitor the latest evidence to ensure that the medications we use are safe and effective. We would not deny any medication that improves life or affects a disease positively.”

Awsare says the drug is under discussion for use on the California formulary by a team of specialists, including a pediatric neurologist, physical and rehabilitation clinicians, and a geneticist, who will make a recommendation to physicians based on risks and benefits.

Physicians will receive these guidelines on prescribing Exondys 51, but Awsare says they make the ultimate decision.

Money matters

The sticker shock of the new drug-an estimated $300,000 per year-has been diluted somewhat by the arrival of many other expensive specialty drugs reaching the market in the last five years.

Awsare says that while the new drugs for hepatitis C-Sovaldi (sofosbuvir) and Harvoni (ledipasvir and sofosbuvir) sell for close to $100,000, they had good evidence to back them; however, he admits that some other specialty, high-cost drugs have been approved conditionally by the FDA through its accelerated approval process, Avastin (bevacizumab) for the treatment of malignant brain tumors among them.

“In addition, as an integrated healthcare system, members have a single premium to use on both medical and pharmacy services so an expensive drug could prevent other patient care,” he says.

Awsare points out that benefits of Exondys 51 are not as obvious as a drug that lowers cholesterol and prevents hearts attacks or strokes-a “no brainer,” he says.

Next: What does Anthem think?



Anthem says ‘no’

Lori McLaughlin, an Anthem spokesperson, says that the FDA label cites that a “clinical benefit” of Exondys 51 has not been established.

“In reviewing the medical literature, Anthem’s Medical Policy & Technology Assessment Committee (MPTAC), a majority of whom are external physicians, determined that Exondys 51 failed to show it improves health outcomes, and therefore it is not a covered benefit for member and employer-sponsored plans and other plans that follow our medical policy,” she says.

She says that Anthem will continue to review new clinical information, which Sarepta recently provided, at its next quarterly MPTAC meeting. 

Approval with conditions

Humana and UnitedHealthcare chose to include Exondys 51 on their formularies but with strings attached.


Humana’s Pharmacy and Therapeutics (P&T) Committee determined that Exondys 51 meets an unmet medical need because there is a lack of effective alternative therapy for the treatment of DMD. The drug requires approval on a member-by-member basis, at which time the insurer looks for appropriateness of the treatment per the FDA label.

Maria Renneke, a spokesperson for Humana, says that the P&T Committee meets often to evaluate all drug coverage polices as new evidence becomes available. Exondys 51, like all drugs, is subject to re-evaluation based on new data.

At UnitedHealthcare, commercial health plan members who are ambulatory and meet other clinical coverage requirements will be able to receive Exondys 51 for treating DMD under the medical benefit. “This prior authorization will help ensure appropriate coverage, given the limited clinical evidence supporting the effectiveness of this treatment,” says a spokesperson.


Mari Edlin, a frequent contributor to Managed Healthcare Executive, is based in Sonoma, California. 

Related Videos
Related Content
© 2024 MJH Life Sciences

All rights reserved.