Making muscles with the most expensive drug in the world
LEAGUE CITY, TEXAS — On a cloudy April day, several weeks into the coronavirus pandemic, pharmacist Jordan Burdine packed up a loaded syringe and buckled it into the passenger seat of her black Lexus SUV.
Burdine was transporting the medicine from a University of Texas Medical Branch pharmacy to a clinic a few miles down the road. Blaise Shumate, a 3-month-old boy with grayish blue eyes and a slow, shy smile, was waiting to receive it.
Two weeks earlier, Blaise had been diagnosed with a genetic disorder that was destroying the motor neurons in his tiny body. These essential nerve cells send messages from the brain and spinal cord that tell muscles to contract; without these messages, muscles begin to atrophy. Left untreated, Blaise would never be able to lift his head, sit up or walk. Eventually, he would lose the strength to breathe.
Burdine was hand-delivering the syringe to an infusion suite staffed by a team of women who had moved heaven and Earth in the midst of a global health crisis to provide Blaise with the best care available. The UTMB pharmacist was more anxious than usual, because the 37 milliliters of medicine sitting next to her came with a staggering price tag: $2.125 million.
She was chauffeuring the most expensive drug in the world.
A Facebook message
Blaise Miles Shumate was born on Jan. 7, 2020, at 9 pounds, 14 ounces.
First-time parents Kenzie Reeder and Cody Shumate finished setting up his black-and-white nursery—with original art made by Reeder’s mom, sister and best friend, Danielle—the night before he was born. Weeks later, nesting in their cozy apartment near Webster, the new mom and dad began to grow concerned about their baby’s development.
“We’d pick him up and his arms and legs would just flop backward,” Reeder said. “We were also worried about his head control really early.”
At Blaise’s two-month checkup in March, his primary care physician confirmed that he had hypotonia—decreased muscle tone—and scheduled an appointment with a neurologist for June.
Soon after the checkup, though, Reeder joined a hypotonia support group on Facebook, where she posted a photo of Blaise with his hands on his chest, wrists and fingers flexed out and away from his body. Stacy Pokorny, a member of the group, shot Reeder a message on April 6:
Not trying to scare you as I know how stressful things can be, but do you know if SMA (spinal muscular atrophy) is on the newborn screening in your state? Do you notice any issues with his breathing or swallowing? If any of these, please research SMA and if symptoms fit call neurologist and tell them you are worried it may be this and see if they will order the blood test. Early treatment is soooo very important and life-saving!!!
Pokorny’s daughter had been diagnosed with SMA type 1; the familiar orientation of Blaise’s wrists in the photo had prompted the mom to reach out.
Alarmed, Reeder went straight to Google.
“The first thing that pops up is the life expectancy of a child with SMA type 1, and it tells you a year to two years,” she said. “It feels like you’re attending your child’s funeral.”
Heart racing, Reeder called her doctor and got an appointment with a neurologist on April 9.
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Diagnosis by Zoom
Although she’d been holding telehealth appointments for weeks, UTMB neurologist Pamela Lupo, M.D., decided to see Blaise in person. She needed to touch his arms and legs, to feel his muscle tone. Immediately, Lupo was concerned.
“Normally, when you pick a baby up they’ll kind of contract and help you hold them and curl up a little bit, but SMA babies just kind of hang there and fall through your hands. Their muscles feel really mushy, like dough,” Lupo said.
The last time the neurologist had seen a baby with SMA type 1 was five or six years earlier, when there was no treatment for the genetic disorder. All doctors could do was provide comfort for patients and emotional support for families.
Lupo ordered rush SMA testing for free through Invitae Lab. Then she messaged colleague Erin Cooney, M.D., a UTMB medical geneticist.
Cooney’s Zoom meeting with Reeder a few days later was supposed to prepare the new mom for the possibility of an SMA diagnosis. Just before Cooney hopped on the call, though, Lupo texted to say that the blood test had come back positive.
“I haven’t even met mom face to face and now I have to deliver this news over a telemedicine visit,” Cooney said. “I got Dr. Lupo on the call and we were able to say: Yes, the test is positive for SMA. But then the called dropped out. Frozen. Worst case scenario.”
Somehow, Reeder knew this was coming. “I woke up the morning of the appointment with Dr. Cooney and I said to Cody, I feel like we’re going to find out something today,” she said.
Minutes after the Zoom fail, when the doctors reconnected with Reeder, they asked if she needed time to process the diagnosis.
“No,” Reeder replied. “Let’s come up with a game plan.”
Every second counts
Most people have two copies of nearly every gene in their bodies—one from their mother and one from their father. Survival motor neuron genes, known as SMN1 and a SMN2, are in charge of making a protein that is essential for regular body movement. SMN1 genes take care of most of the SMN protein a body needs, while each copy of the SMN2 gene kicks in about 10 percent.
People born with one non-functioning SMN1 gene are carriers of spinal muscular atrophy, yet display no symptoms. But if two carriers have a child together, there is a 25 percent chance that the child will inherit both non-functioning copies of SMN1 and be diagnosed with SMA.
That’s what happened to Blaise Shumate.
Spinal muscular atrophy affects about 1 in 10,000 live births, according to the National Organization for Rare Disorders. SMA types range from 0, the most severe—these babies don’t leave the NICU—to types 1, 2, 3 and 4, which denote decreasing degrees of muscle weakness.
“All these kids need to be evaluated by a lung specialist,” Lupo said, “because muscles help support your lungs.”
The severity of the disease depends on how many copies of the SMN2 gene a patient has, said Tim Lotze, M.D., director of the Muscular Dystrophy Association Comprehensive Care Center at Texas Children’s Hospital and a professor of pediatric neurology at Baylor College of Medicine. If a patient happens to have four or six or eight copies of the SMN2 gene, which is not uncommon, more SMN protein is being produced and it takes longer for symptoms of muscle weakness to show up in the body.
Blaise has just two copies of the SMN2 gene, which is why his symptoms appeared before he was 6 months old.
“The take-home point is: The sooner we can give the patient treatment, the better,” said Lotze, who has seen close to 200 babies with SMA over the past two decades.
For Blaise, every second counted. Motor neurons he needed for breathing, sitting and walking were dying every day. Doctors needed to stop this ticking clock.
Cooney explained both available SMA treatment options to Blaise’s parents.
One was a prescription medication, Spinraza, which works with the SMN2 gene to produce more motor neurons in both pediatric and older patients. Spinraza is injected by needle into the spinal fluid of a patient’s lower back. After a two-month ramp-up with four loading doses, patients get maintenance injections of Spinraza every four months for the rest of their lives.
The other option, approved for children 2 and under, is a one-time infusion of Zolgensma, a gene therapy that replaces the function of the non-working SMN1 gene. Zolgensma contains a gene and a vector. The gene is a new, working copy of the SMN1 gene, while the vector—the suitcase that carries the DNA to the cells—is a non-infectious virus. The new gene speeds straight to the motor neuron cells in the body and tells them to start making SMN protein.
(A third option, oral drug risdiplam, was approved by the U.S. Food and Drug Administration on Aug. 7.)
Both Spinraza and Zolgensma have proven to be effective.
“We do not have any direct comparative studies,” Lotze said. “I think the best we can say is they both work.”
Often, the option parents choose depends on how they feel about long-term vs. short-term treatment, he added.
“It seems to me, some people think a medicine works better if they are continuing to take it,” Lotze said.
Kenzie Reeder and Cody Shumate weren’t those people. They liked the idea of a one-and-done drug. Zolgensma seemed easier to manage and less painful for their baby. Plus, Reeder’s Facebook friend Stacy Pokorny had treated her daughter with Zolgensma and raved about the results. In the midst of a pandemic caused by a virus, this drug was a reminder that some viruses can be harnessed for good.
Still, there were no guarantees about Blaise’s mobility. Every case is different.
“Even in the clinical trials for Zolgensma, it’s not necessarily the case that every patient was spot on and started walking at 12 months,” Lotze said. “Some were delayed even past 18 months. I tell families you shouldn’t necessarily expect that your child will achieve walking, but we may expect them to sit independently, which is certainly important.”
Because UTMB had never done gene therapy, there was no protocol for Blaise’s treatment. Cooney assured Blaise’s parents that she and her colleagues were more than up to the task, but mom and dad needed to understand that Blaise would be a pioneer—the recipient of the first gene therapy ever delivered at UTMB.
Texas Children’s Hospital had treated several babies with Zolgensma, but TCH didn’t accept Blaise’s Amerigroup Medicaid health insurance. Transferring coverage to a form of Medicaid TCH did accept would take 45 days—precious time for a baby with spinal muscular atrophy.
Cooney and Reeder were texting several times a day at this point, sometimes late into the evening. Cooney encouraged the new mom, who was home all day with her baby, to reach out with any questions or concerns. Reeder’s husband, who is employed by a rental equipment company, often works long days and weekends.
After weighing her options, Reeder decided to stay with UTMB for the therapy. Cooney’s team hustled to send Medicaid a 30-page “prior authorization” packet, which included lab reports, clinical notes and a letter of medical necessity.
Everyone expected to wait days or even weeks for a response. The pandemic had thrown working life into a strange “new normal” that didn’t feel normal at all. People were working from home with spotty internet access while trying to manage interruptions from children and pets. No one knew if the pandemic would make it easier or more difficult to get Blaise the help he needed.
Meanwhile, Reeder and Shumate were at home, watching their baby regress. “We saw him getting weaker,” Reeder said. “We were having feeding issues.”
Incredibly, Medicaid responded within 24 hours.
Trying to control the emotion in her voice, Cooney called Reeder to tell her that Medicaid had approved Zolgensma for Blaise. That evening, Reeder wrote on her Instagram feed: [Blaise’s] doctor called me almost in tears saying insurance had approved us within hours instead of days! … I’m in tears all over again writing this, knowing Blaise can have this miracle drug in his veins.
Behind many successful new ventures is one person who wrangles all the key players and pushes through mountains of forms, approvals and checklists until the goal is met. For Team Blaise, that person was Allison Britt, a genetic counselor at UTMB who works with geneticist Erin Cooney.
Britt kept track of all the moving parts and more than 20 people—herself, Reeder, Cooney, Lupo, Burdine, UTMB pharmacy leadership, the specialty pharmacy representative, UTMB clinical leadership, Zolgensma representatives, Medicaid case managers and UTMB’s finance team—who played a role in Blaise’s care.
“It took about 140 emails,” said Britt, who actually counted them, “but everybody wanted to be a part of it. As soon as you put the clinical information into their hands, people started opening doors.”
AveXis, the company that makes Zolgensma, walked Britt through a multi-step process. Not only did UTMB’s pharmacy need to be listed as a site of care for the drug, but an infusion nurse needed training in how to administer it.
And then there was the matter of cost. Like every other health system that had scaled back on elective surgeries in order to focus on COVID-19 care, UTMB was facing its own financial challenges. And now, Medicaid had approved a $2.125 million drug for one of its patients.
“There are two ways you can acquire this drug,” Cooney explained. “One is that you buy it and then bill insurance. There’s also a third-party pharmacy way where the third party pharmacy takes the risk.”
Medicaid’s approval of the drug meant that Medicaid had agreed to pay an “allowable amount” for it, not necessarily the total cost. Any difference between the “allowable amount” and total cost had to paid by UTMB or a third party.
While UTMB financial leaders weighed the two options, Britt and Cooney stayed in constant touch with them, at one point sending a nudge-y email along the lines of: Guys, our name tag is on each motor neuron this child is losing. Every second counts. It doesn’t matter how we get this drug. We just need it. Now.
UTMB’s finance team finally opted for a third party pharmacy and Team Blaise found one: Orsini Specialty Pharmacy, based in Illinois.
With the gene therapy infusion scheduled for April 28—just two weeks from the day that Blaise had been diagnosed—all the pieces started to fall into place.
The specialty pharmacy sent Blaise’s frozen dose of Zolgensma by air from Chicago to Houston’s George Bush Intercontinental Airport on Monday, April 27. The medicine arrived in the morning and was picked up by special courier and delivered directly to UTMB’s pharmacy in League City. Glamorously, the Zolgensma was packaged with a $15,000 tracking device—the $2.125 million medicine would not be misplaced.
The infusion took place on Tuesday, April 28, 2020. Every minute of the day was scheduled precisely. At 8:30 a.m., pharmacist Jordan Burdine removed the Zolgensma from the refrigerator at the pharmacy. At 10:30 a.m., Blaise and his parents arrived at UTMB’s League City Pediatric and Specialty Care Clinic, located on the second floor of a strip mall. Blaise wore a white T-shirt that said, “Installing muscles … please wait,” and Britt had made gene cookies for everyone to nibble on.
Blaise was fitted with two IV access lines, in case the first one malfunctioned. Infusion nurse Janice Nolan and nurse Crystal Deem worked with phlebotomist Ana Linda Garcia to gain access to the baby’s veins, but Blaise was a “hard stick.” They tried his arms, hands, feet—no luck. The trio wanted to try the veins in his scalp, but Reeder broke down when this option was presented; it was too terrifying to think of a drug flowing directly into her baby’s head. Reeder finally conceded, but stepped out of the room for the procedure, leaving her husband to stand watch. Happily, both scalp veins offered excellent access. When the nurses taped the lines to the top of the baby’s head, he looked like he had tiny cat ears.
By 12:30 p.m., the IV lines were finally ready and the clinic notified Burdine at the pharmacy, who drew the Zolgensma into a syringe. Once drawn, the drug must be used within eight hours. Burdine buckled the medicine into the passenger seat of her SUV and made her way 2.6 miles to the clinic, crossing Interstate 45. When she pulled in, Britt was waving from the balcony. They entered the clinic triumphantly, with Burdine carefully brandishing the precious medication.
“You can’t tell because we are all wearing masks, but everyone in the whole clinic has huge smiles on their faces,” Britt recalled. “It’s hard to suppress the urge to hug everyone who had been involved in making this treatment a reality.”
For the first time, Kenzie Reeder and Cody Shumate met their son’s entire medical team in person. Reeder offered everyone a heartfelt thanks.
The 60-minute infusion began at 1 p.m. in a quiet corner room with windows. Reeder sat in a recliner with Blaise dozing in her arms. The 37 milliliters of Zolgensma that was flowing into Blaise’s body would halt the progression of SMA type 1, protect and strengthen the motor neurons he has and, perhaps, make some new collaterals. At one point, Blaise woke up and watched some SpongeBob SquarePants on an iPad before nodding off again. Overall, the hour was blissfully uneventful—such a short amount of time and such a small amount of medicine to change the course of someone’s life.
Early Diagnosis and Newborn Screenings
Today, prenatal or preconception carrier testing can identify roughly 200 genes of the most common recessive disorders, including spinal muscular atrophy. This type of testing is not standard, though, and there’s a good chance it won’t be covered by insurance.
Approximately one person in 50 is an SMA carrier.
“We have pushed to make carrier testing part of what’s offered to every woman at UTMB as part of their OB-GYN care,” Cooney said. “We have genetic counselors who are available to any woman—regardless of age or medical background—to do a full family history and talk about what they could be at risk for.”
But both Cooney and Lotze, who are involved with the state’s Newborn Screening Advisory Committee, said SMA should be part of Texas newborn screening by next summer.
“It’s a really big deal, Cooney said. “It will catch SMA in infants born in Texas within the first few weeks of life—instead of only making the diagnosis once symptoms are obvious and a clinician thinks to test for SMA.”
August is SMA Awareness Month, a recognition launched by Cure SMA.
“It’s an opportunity to spotlight the disease but also to put a spotlight on the SMA community and its accomplishments,” said Leslie Humbel, senior director of marketing and communications at the nonprofit. “A lot of people have never heard of SMA. It’s not only unexpected, but unknown.”
Years ago, when a family received a diagnosis of spinal muscular atrophy, the message was: Take your baby home. Love them and care for them, she added.
“Today, the message is very different,” Humbel said. “We now have three forms of treatment.”
Blaise at 7 months
On a padded mat in the center of the family room, Blaise practices rolling over. He is stretched out on his side and mom is coaching him, helping him lift and then swing his outside leg forward. “Current Family Favorite” is the message emblazoned on his tiny T-shirt this August afternoon.
“Good job!” Reeder says, when he manages to flip himself over and onto his stomach.
Next comes “tummy time,” which allows Reeder and Dianna Lewis, LVN, a nurse who’s been coming to the home to help, work Blaise’s neck muscles. They place him stomach down, his head and arms slightly elevated over the side of a pillow, to encourage him to lift his head.
At 7 months and nearly 17 pounds, Blaise has a soft crown of golden hair and a calm demeanor. Reeder started to see changes in his body just days after the gene therapy.
“He was laying on me and he started lifting his leg all the way up,” she recalls. “And then he was kicking his leg up. I was just sobbing. All he could do before was just scoot his legs across the floor. He had never picked them up.”
Blaise’s hands are improving, as well.
“He completely grabs toys now,” Reeder says. “He’ll wrap his hand around a ring and pull on it. He sucks his thumb.”
In May, Blaise spent nine days in the hospital, where he was outfitted with a feeding tube.
“He breathes great on his own, but he hadn’t gained weight in two months,” Reeder says. “What we discovered from the hospital stay is, his body was working so hard to breathe and eat that he was burning all his calories.”
The family moved to a three-bedroom house in Spring in July. They wanted to be closer to Shumate’s job and they had outgrown their apartment.
“I think we underestimated how much stuff was going to come with Blaise—and then you add in medical equipment,” Reeder says.
The black and white nursery has been reassembled in the new house. Under photos and wall art adorned with playful messages like “Epic Kid” and “Welcome to My Crib,” an array of equipment sits at the ready. For months, Blaise has used a Trilogy bi-level positive airway pressure (Bi-Pap) ventilator when he sleeps at night.
Twice a day, Blaise receives breathing treatments in his nursery. On this August afternoon, Lewis begins with a nebulizer that delivers a mist of medication to his lungs to help break up mucus. Because he’s teething, Blaise also spends a few minutes chewing on the nebulizer mask. Lewis then uses a small mallet to tap vigorously on his chest and back to further dislodge any gunk.
Step 3 is the cough assist machine, which pushes air into Blaise’s lungs to force small coughs. Blaise hates it, Reeder says; as if on cue, he starts whimpering.
“I’m sorry, baby,” Reeder coos, while Lewis holds the mask to his mouth. Reeder counts from one to five several times when the mask is in place, holding her baby’s hand throughout.
A quick suction to pull out the mucus caps the four-part, 25-minute treatment.
“A day in the life of Blaise,” Reeder says.
The children who were part of Zolgensma’s clinical trials are only 5 or 6 years old today, so it is too soon to draw conclusions about long-term health. But it’s clear that the gene therapy has offered a quality of life they never could have achieved without treatment.
“Knowing that these children are all alive and not on a ventilator is a massive win,” Cooney says. “These are kids with normal cognition. They can read and have friends and go to school. I told Kenzie I want an invitation to Blaise’s wedding.”
Kenzie Reeder, of course, has dreams large and small for her firstborn. She hopes to see him eating independently by the time he turns 1, and she hopes he can do a “cake smash” on his first birthday. More than anything, she wants to see him walk.
“I also worry about little, silly things—like I worry about him getting bullied,” Reeder says. “But what parent doesn’t worry about that?”