Bring Me to the Payers – The Fight for Access to Exondys51

Devin walks the school’s halls full-time at 15 1/2 years old.

“The Day”
On September 19, 2016, the US Food and Drug Administration (FDA) approved the first ever treatment for Duchenne Muscular Dystrophy. Eteplirsen, otherwise known by its brand name Exondys51, was developed by Sarepta Therapeutics. Exondys51 is a novel medicine that uses a technique called exon skipping which allows an error in mutated RNA to be skipped over so a truncated version of dystrophin can be created.

A little bit about the science
I don’t want to go too far into the technical aspects of how or why Exondys51 works, but I think a brief and basic understanding is necessary. Duchenne Muscular Dystrophy (DMD) is characterized by progressive loss of strength throughout the entire body. Boys (and in very rare cases girls) that are diagnosed with DMD are not able to produce a protein known as dystrophin. Dystrophin is a protein that is part of a complex that stabilizes muscles and protects them from damage. The gene that codes for dystrophin is the largest in the body, making it more prone to error. There are 79 exons in the DMD gene and a coding error in certain exons or a combination of exons can cause DMD. The mutations in the gene can be inherited or they can be spontaneous. The complexity of this particular gene make spontaneous mutations common. In fact, my son Devin has what’s known as a deletion and is missing exons 48, 49, and 50. His mutation was spontaneous. I wanted to share his deletion with you so you can see how the exons are organized using the graphic below.

This image represents the organization of the 79 exons that make up the DMD gene.

What you see here is just a representation of the 79 exons in the dystrophin gene. You’ll notice they are all formed in various shapes, but that’s just for demonstration purposes. Recall that Devin is missing exons 48, 49, and 50. Without Exondys51, exon 47 would be trying to match up with exon 51 since he doesn’t have exons 48,49 and 50. As the diagrams shows, exon 47 and exon 51 do not match up. However, Exondys51 is able to attach to exon 51 causing it to be skipped over which allows exon 47 to connect to exon 52. Tadaaa! The result is a set of instructions that can be read and are able to produce a dystrophin protein. The protein it produces isn’t the full length, but that may not limit its effectiveness. It is fact that Exondys51 produces dystrophin. It has been verified in trials using a technique known as western blot to show a complete absence of protein (or a minuscule amount of protein in a few instances) prior to exposure to Exondys51 and the presence of dystrophin after treatment with Exondys51.

The FDA agreed that the medicine did its job in terms of demonstrating the ability to produce dystrophin. There is no question – Exondys51 induced the production of dystrophin in boys who were otherwise unable to produce dystrophin naturally.

The Pathway to Approval and Other Legal Stuff

I think it’s important to look at the process Sarepta took in applying for approval in order to understand what qualifies for each designation. The programs that have been put in place are there for good reason and the value of the medicines that qualify for these programs needs to be recognized.

There are in fact two pathways for a drug to obtain approval; Traditional Approval and Accelerated Approval. It’s important to note that according 21 C.F.R. Sec. 314 Subpart H, a drug that receives approval by way of either pathway is in fact an FDA approved drug for use in the patient population as indicated. There are additional requirements for drugs approved via the accelerated approval pathway that will be covered below, but that does not qualify the drug as investigational; that term gets dropped once it is approved for use.

The FDA instituted the Accelerated Approval regulations in 1992. These regulations allowed drugs for serious conditions that filled an unmet medical need to be approved based on a surrogate endpoint. Using a surrogate endpoint enabled the FDA to approve these drugs faster.  ***DMD is a terminal disease without any treatment options.***

In 2012, Congress passed the Food and Drug Administration Safety Innovations Act (FDASIA). Section 901 of FDASIA allows the FDA to base accelerated approval for drugs for serious conditions that fill an unmet medical need on whether the drug has an effect on a surrogate or an intermediate clinical endpoint.  ***DMD is a terminal disease without any treatment options. Detection of dystrophin induced by treatment can be considered a surrogate endpoint.***

A surrogate endpoint used for accelerated approval is a marker – a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. Likewise, an intermediate clinical endpoint is a measure of a therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on irreversible morbidity and mortality (IMM).  ***DMD is a terminal disease without any treatment options. Detection of dystrophin induced by treatment can be considered a surrogate endpoint. DMD is characterized by a lack of dystrophin. Therefore the presence of dystrophin is reasonably likely to predict clinical benefit.***

Drugs that qualify for accelerated approval must:

A.  The disease is a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years, including age groups often called neonates, infants, children, and adolescents.  ***DMD is terminal and manifests at birth.***
B.  The disease is a rare disease or condition, within the meaning of Section 526. Section 526 defines rare as affecting less than 200,000 people in the United States.  ***There are approximately 20,000 people diagnosed with DMD in the United States (there are many more affected by the disease)….although this medicine could go a long way toward changing that***

Exondys51 rightfully received fast track designation.

Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions. *** DMD is obviously one of those conditions.***

The Result

I hope you’re still with me even after trying to sum up all that complicated legal stuff and through my attempt at making science based explanations understandable. Dr. Janet Woodcock M.D., Director of the FDA’s Center for Drug Evaluation and Research summed it all up best when she said“Patients with a particular type of Duchenne muscular dystrophy will now have access to an approved treatment for this rare and devastating disease.” That is certainly easy to follow and news that should make anyone cheer! We’ve been waiting far too many years to hear those words. To me, it was a confirmation of answered prayers!

Devin and his incredible care team celebrating his completion of the phase 3 trial of Exondys51.

…but the battle is still just as fierce now? How can that be?

(I’ll do my best to be brief about something for which I have so much to say.)

What you should know is that Anthem Blue Cross Blue Shield serves 1 of every 8 Americans or over 73 million American lives. They are the second largest insurer in this country and therefore it’s reasonable to assume they also insure quite a few people living with DMD. Anthem’s official stance on paying for Exondys51, “The use of eteplirsen is considered investigational and not medically necessary for all indications, including but not limited to the treatment of Duchenne muscular dystrophy.”  In short, Anthem’s stance on paying for Exondys51 is, nope not happening. Yes there is an FDA approved treatment for Duchenne Muscular Dystrophy, but “we” will not pay for you to receive it.

United Healthcare operates Optum Healthcare serving over 115 million Americans. Optum was providing coverage of Exondys51 to qualifying boys with DMD, but as of April 1, 2017 the qualifications became more strict (and more unethical) since they will no longer be providing Exondys51 to boys who are unable to walk. There are boys who have been receiving the medicine commercially with Optum coverage who will now have to terminate use and revert to managing their DMD without an effective alternative treatment.

I highlighted some of United Healthcare’s qualifying criteria below. The link provided goes to the full document.

Exondys 51 (eteplirsen) may be covered for:

1. The treatment of Duchenne muscular dystrophy (DMD) in patients who meet all of the following criteria:

a. For initial therapy, all of the following:

(3)  Submission of medical records confirming that the patient has a 6- Minute Walk Time (6MWT) ≥ 300 meters while walking independently prior to beginning Exondys 51 therapy.

(6)  Initial authorization will be for no more than 4 weeks.

b. For continuation therapy, all of the following

(2)  Submission of medical records confirming that the patient is ambulatory (can walk) without needing an assistive device (e.g., cane, walker, wheelchair).

(4) Reauthorization will be for no more than 6 months

Express Scripts is used by Anthem Blue Cross Blue Shield to provide my family’s pharmacy care. Here is a screenshot of their drug exclusion list along with a link to the full document:

The Express Scripts exclusion list document shows all the medicines they refuse to cover and then provides an alternative medicine to use. What do they have listed next to Exondys51 as the alternative treatment? Nothing? You mean they cannot offer an  alternative to this serious disease? That reminds me of a medicine that would qualify as, “Filling an unmet medical need by providing a therapy where none exists.”

Just a little more about us personally

Devin’s mother and I were never married. We share equal custody and placement is divided at exactly 50%. We are entirely equal. The standard for coordination of insurance benefits determines her insurance is applied to Devin’s healthcare expenses first since she is older than me (strange policy). We both carry insurance on him and, as luck would have it, we both have policies with Anthem Blue Cross Blue Shield.

Devin’s mom works for the United States Post Office and the policies negotiated with Anthem are different than the policies that apply to the group I belong to. I don’t know exactly how it works according to their policy, but her insurance covers Exondys51 for him and mine does not!

Proof of my coverage on him.
Proof of his mom’s coverage.







How is it possible for Caremark to approve the use of Exondys51 even before the FDA has approved the application?

Her pharmacy insurance benefits are managed by Caremark on behalf of Anthem. Anthem uses Express Scripts to manage mine. One thing I find very interesting is the idea that Caremark approved Devin’s use of Exondys51 before the FDA had even approved the drug for commercial use. As shown in the image above, his approval for use of Exondys51 from Caremark began on 8/22/16 even though the FDA didn’t approve Exondys51 until 9/19/16. How is that even possible? I’m speculating, but perhaps it was done to bring his renewal date in closer. The drug is expensive and clearly not a cost insurance companies want to pay. Setting his approval date as early as possible also means the date to apply for renewal comes after fewer times actually receiving the medicine commercially. In doing so, they reduce the total expense paid because the qualifications for renewal are very difficult to meet. As noted above, in order to qualify for renewal of coverage, Devin will either have to undergo surgery to measure the amount of dystrophin present via muscle biopsy or he’ll have to increase the distance he is able to walk during a 6 minute walk test. Devin did not have a biopsy (other than as part of the trial) to establish the baseline level of dystrophin present in his muscles prior to beginning the commercial dosing regimen, so in all likelihood, he’d have to qualify based on his performance as determined by the 6 minute walk test. Anthem is requiring an increase in the distance walked even though boys with DMD who are 16 years old are not known to increase their walk distance (let alone be walking in the first place). The requirement that this drug make that feat possible as a standard does not align with the expectations the community has for Exondys51 based on firsthand observations, trial data and documented natural history of DMD.

Furthermore, because Devin was in the phase three trial, he didn’t even begin commercial use until after he completed the trial and after the local infusion site was fully prepared to begin administering this completely new medicine. Devin received his first commercial dose of Exondys51 on March 3, 2017. Anthem BCBS essentially pre-approved him from March 3, 2017 to October 21, 2017. The duration of the approval will cover only 34 doses of Exondys51 versus the standard 52 doses required for a full year of treatment. Make no mistake about it, Anthem and Caremark expect that October dose to be the last commercial dose for Devin, my son.

What’s next?

This entire scenario is absolutely outrageous! We, as a community, have to do something about it. I’m not just referring to insurance coverage of Exondys51 or other DMD drugs either for that matter. “Insurance Bullying” (I think I just made that term up) knows no boundaries. My heart aches hearing about friends who’ve been at the mercy of insurance while trying to obtain Spinraza to treat Spinal Muscular Atrophy (SMA). I have family who’ve been denied access to medications and surgeries their doctors tell them they need in order to treat their cancer. This type of situation is having an affect on many health conditions and it happens across the entire country.

Do insurance companies only offer coverage of any value to healthy individuals? Subscribers pay appropriately for their insurance policies, but are unable to trust they’ll receive the benefits they require when the need arises. Insurance companies want to tell us about clinically meaningful – We need to examine insurance coverage more closely and define it in terms of beneficially meaningful! Coverage like this needs to be stamped “unapproved” and forbidden to be sold to anyone on the basis of lack of efficacy!

Please understand, I’m totally okay with capitalism. I can interpret company financial statements and I fully understand the primary role of management is to increase company value with the responsibility to maximize earnings for shareholders . I support compensation for taking the risk these insurance companies are supposed to be exposed to however, all I see at risk is the health and lives of the policyholders! Earning dividends in such a way is utterly shameful!

Attention Anthem, United Healthcare, Excellus BCBS, et al. – Change isn’t just something that’s on the way, something to consider or prepare for. I’m not talking about change or rallying support for it. The change we desperately need has ALREADY BEGUN! If you’ve failed to recognize that, you failed your policyholders. In doing so, you’re part of the problem and have committed yourself to becoming part of the past. Devin often recites the following line from Spiderman, “With great power, comes great responsibility.” He learned long ago what that meant in the Marvel Universe, but is still learning its meaning today by the examples he observes in the world around him. I can’t express the disgust I feel knowing that he’s learning about the influence money and power can have on such critical decisions including some that directly affect the health of people he knows and loves. How do you explain to a child that somebody holds the potential to improve their health and provide added time to experience life more fully with their loved ones, but instead chooses to serve themselves?

DMD Families: I’d like to post testimony and pictures of people affected by these types of decisions. Please share a comment below if you feel comfortable. I’ll be forming something more formal soon, but in the meantime, please follow Devin’s Facebook page since it’s where we share most often. We are going to deliver these changes together. We’ll do it with the help of advocacy organizations and all the resources they can provide or we’ll simply get it done on our own, grassroots style. This effort won’t require the consumption of expensive resources we don’t already have readily accessible to us. People understand and relate to our testimony. They understand the urgency of our need and are upset when they learn about the of denial of Exondys51 coverage that could save the lives of our loved ones. The facts are facts and the evidence is available for anyone to see, but it hasn’t reached quite enough people to push the momentum beyond the tipping point. We just need to be heard!

To anyone reading this: You can be sure I didn’t write this for my own benefit or for that of my family – not in the least bit. This article was inspired by my experience observing the operation of a broken system knowing the damage it’s doing to the lives of people in need and the feelings of compassion I’ve had for everyone who has been mistreated by it. In short, this article is written about a system that functions on lies, motivated to attain maximum company earnings without genuine regard for the countless number of hearts it’s broken along the way. It must be stopped! …and it will.

Written By: Josh Argall

Father of Devin, a 15 1/2 year old boy living with DMD.

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