Hope or Heartbreak?
September 23, 2019
Gene therapy has been around for a long time, longer than many current nurses have been licensed. The science isn’t new. What is new is a drug that treats the most lethal genetic illness of children under the age of two, an illness known as spinal muscular atrophy or SMA type 1.
With SMA, children lack a protein (SMN) which stands for survival of motor neurons. Without this protein, babies are unable to gain normal developmental markers within weeks of birth, and will exhibit a weak cry, failure to thrive, a tendency to aspirate, and difficulty with suckling. They may be unable to nurse or reveal respiratory distress. Without supportive therapy, babies with the most severe form of the genetic defect generally do not survive past the age of two. Imagine if a drug that comprises a complete cure for this disease could be placed on the market!3
In May of this year Zolgensma, (onasemnogene abeparvovec-xioi) was approved by the FDA. This gene therapy drug offers a cure for children with SMA type 1. The drug is given via infusion, and it is curative, unlike a treatment drug that was offered previously. The only drawback?3
The initial price point for Zolgensma has been set at a startling $2.1 million per infusion. Yes, you read that correctly. The infusion costs $2.1 million. It is given once, and it must be given early in the disease process for a baby with the disease, for every week that a child with SMA type 1 goes without the protein they require, more axons are dying, and they will not regenerate once they are gone.
Once the infusion is given, the difference is startling, yet insurance companies are balking. Novartis, the pharmaceutical company behind the promising therapy, was initially confident, yet only one-third of U.S. insurance companies have made decisions about how to proceed with the lifesaving therapy. Analysts at one influential Wall Street firm (Bernstein) have voiced concern. Payer concerns for Zolgensma may be a boon to a similar product, Spinraza, that is given multiple times over a patient’s lifetime but does not offer a cure. This drug, offered by Biogen, costs $750,000 for the first year and up to half that amount for cumulative years of treatment.2
It appears insurance companies might not be looking much further than the initial sticker shock. Gene therapy is hardly cheap. Luxturna, often considered the “first true drug” of gene therapy, while being spearheaded in Europe, has cost Novartis over $100 million to acquire U.S. rights for marketing. The drug was approved to correct a rare type of blindness, called mutation-associated retinal dystrophy. The initial price point was set at $425,000 per eye, or $850,000 for both eyes.4
But how did we get to this point and place in time, where we are able to cure a genetic disease with a single infusion?
For nurses who have been fans of Jason Bourne movies, the subplot was always about creating a superhero through genetic therapy. While the movies were fiction, many of the ideas in The Bourne Legacy were based on truth. Gene therapy involves the use of a vector (virus) which is introduced into the host for the purpose of carrying therapeutic genetic material.1 The virus should be harmless, and serve merely as a carrying agent, replicating itself over and over once in the host. However, as in the movie, this didn’t happen in the early days. Just as actor Jeremy Renner became dreadfully ill in the movie when the virus was loaded, so did a patient.
In 1999, a distressing event occurred at the University of Pennsylvania during a clinical trial when an experimental gene was delivered via the use of an adenovirus. While the vector should have been harmless to the host, this event turned tragic, as the patient, Jesse Gelsinger, only 18 at the time, died of colossal organ failure as his body formed a massive immune response to the virus.4
Hospitals discontinued gene therapy trials for a time after Jesse’s death. It was a desolate time. Ethicists were troubled by the idea of manipulating and correcting genetic mutations, but ultimately, science prevailed. By the years 2000-2018, approvals occurred in both Europe and the United States. A drug deemed the “most expensive failure” was approved to treat pancreatitis in 2015, but at $1 million, no one could afford to pay for it, and it failed. Another drug, approved in Europe for ADA-SCID, a rare genetic disorder that causes severe combined immune deficiency, was initially priced at $665,000. As of 2018, only 5 patients had been approved for treatment with this drug, and the pharmaceutical company subsequently sold the drug to another firm, believing it too expensive to maintain.4
This sets a very important precedent for gene therapy pharmaceuticals. What will the market bear? Keep in mind these drugs may offer the patient a cure as opposed to treatment, which is life changing. To understand what a difference this could make, we should examine the life of one of the first children treated with Zolgensma during the clinical trials.
Malachi Anderson is four years old, and although he can’t walk, he continues to grow stronger every day. The sixth child of Tina and Torrence Anderson came into the world on July 31, 2015. To them, he seemed nearly perfect until eight weeks had passed, then they noticed he wasn’t hitting milestones. He couldn’t move his head like a normal infant or roll over. By the age of three months. Malachi was missing reflexes. Ten days after his first Pediatric check-up, he was diagnosed with SMA type 1. The Andersons found a clinical trial for Spinraza, a drug that might help treat Malachi’s condition, but the trial would mean moving. There was also no promise their son would get the drug as opposed to a placebo, since it was a double-blind trial.5
Getting a placebo would mean Malachi would probably die.
The Andersons found a second clinical trial for a drug that offered a one-time treatment, but Malachi was one of the last babies enrolled. He would be four months and 2 days old at the time of treatment. Luckily for Malachi, he was in the high dose trial, the arm that is now the recommended dose. According to his mother, he mostly slept through the infusion, occasionally glancing around the room. But physical improvements, his parents stated, were visible almost immediately. Malachi began moving his arms and legs more than he ever had, and before they knew it, he was able to sit up.5
For the Andersons, Malachi has a life of possibilities. He is a little boy attending preschool and playing soccer from his scooter. He is a bright, articulate boy with many friends. Although the Andersons received Malachi’s treatment for free, they believe the price tag for Zolgensma is appropriate because the drug is curative, whereas treatment with Spinraza is not curative and must be continued year after year. Additionally, Spinraza must be given into the spine.
But what about those for whom Zolgensma may be denied? In July of this year, “UnitedHealthcare reversed previous denials and approved coverage” for six children, denying public attention had played into a reversal on their decision. UnitedHealth Group’s CEO stated the decision had been based on clinical evidence alone, and not price.6
Other insurance providers disagree. Decisions are being made not only on price point, but also clinical markers. Anthem cuts off coverage after six months. Some patient denials are made if the babies are asymptomatic (too healthy), or too sick and deemed unlikely to benefit from the drug. However, on one of the appeals, a baby was overtired and retested. When testing was repeated, the score was within parameters appropriate for treatment.
Obviously, this drug has the potential to not only save lives, but be life altering. When insurance denials are made, families need assistance in making appeals quickly and efficiently. Time wasted means neurons that cannot be saved and motor development that will not be rescued.
With a $2.1 million price point, we must wonder. Is this new drug a reason to hope, or a false promise? Could this drug bring heartbreak, comparable to the drugs in Europe that proved so expensive for patients they were barely utilized? How many babies with SMA type 1 will be cured?
I really hope this saga ends like a Jason Bourne movie, one with a hero who races in to save the day, and all the vulnerable babies receive infusions. That’s my ending; I hope Wall Street agrees.
Websites:
- Childrenshospital.org “Gene Therapy Program.” Boston Children’s Hospital. 617-355-6000
- Fiercepharma.com “Novartis is Struggling to Win Payer Coverage for $2.1M Gene Therapy Zolgensma; Analysis.” Weintraub, A. July 3, 2019.
- Novartis.com “AveXis Receives FDA Approval for Zolgensma, the First and Only Gene Therapy for Pediatric Patients with Spinal Muscular Atrophy (SMA).” May 24, 2019.
- Risingtidebio.com “The Gene Therapy Sector is Experiencing an Acceleration.”, Curran, K., June 10, 2019.
- Smanewstoday.com “Zolgensma ‘Saved All of our Lives’; A Family’s Journey Through Gene Therapy.” Wexler, M., June 14, 2019.
- Washingtonpost.com “High Fives and Sobs Greet UnitedHealthcare’s Reversal of Denials for Gene Therapy.” Rowland, C., July 18, 2019.
The Bourne Legacy: a 2012 American action thriller movie starring Jeremy Renner, is based on a genetically enhanced superhero, and is considered to be the 4th in the Jason Bourne series.
