Six-year-old Zahra Dehghanipour suffers from a genetic disease that causes her muscles to atrophy. She wears a painful chest brace to stay upright, and has to be carried up and down the stairs in her family’s two-story home.
Her condition, spinal muscular atrophy, has a drug treatment. But her family faces many hurdles in accessing it. Cost is one: The drug, called Spinraza and made by Cambridge, Mass.-based Biogen , costs $750,000 for the first year, and $375,000 annually after that.
She lives in Iran, where the drug hasn’t been approved for use. The government, which pays for a significant part of its citizens’ health care, has approved some U.S.-made drugs, but it hasn’t yet worked out a deal to bring in Spinraza.
Her case illustrates a challenge in modern medicine: Access to lifesaving treatments often depends on accidents of geography. “If [Zahra] were living in the U.S., she would be treated,” says Richard Finkel, chief of the neurology division at Nemours Children’s Hospital in Orlando, Fla., who isn’t involved in Zahra’s case and doesn’t know the family. “It really is a country-by-country situation. That disparity is something that’s certainly bothersome to those of us who feel fortunate to be able to provide this treatment to our patients.”
Her family is desperate to find a way to access the drug. They have asked Biogen for a discount, raised funds to help cover the cost and explored moving to Germany or Turkey, where the drug is available. But all those possibilities are complicated and require navigating bureaucratic and legal obstacles. Every day, her muscle function and respiratory system weaken, the eventual cause of death for most patients. The drug isn’t a cure, but can prevent progression and, in some cases, improve the condition.
“Time is of essence for us,” says her mother, Zeynab Zareinezhad, a teacher and assistant principal at the school Zahra attends, speaking in Farsi. “Her disease is progressive. She loses more cells and neurons day by day.”
Zahra seemed a healthy baby. Her parents didn’t know something was wrong until she was about seven months or eight months old. She sat up and rolled over once but that was it. She couldn’t hold her neck upright anymore either.
SMA is a motor-neuron disease. A motor neuron sends messages to the muscles used for movement in the legs, chest, head, and other parts of the body. In patients with SMA, the motor neurons in the spinal cord don’t have enough of an important protein, so they stop working and eventually die, resulting in a decline in muscle function. Eventually patients have limited use of their hands and may need respiratory support and feeding tubes.
Although a relatively rare disease, SMA in its severest form is the largest genetic cause of death in infants. About 1 in 11,000 children are born with SMA world-wide annually and roughly 1% to 2% of the population are carriers of the genetic mutation, Dr. Finkel says.
After seeing doctors and having a genetic test, Zahra was diagnosed with SMA type 2 when she was 16 months old. Unlike patients with SMA type 1, who often die when they are babies, type 2 patients can live until early adulthood, or later, but eventually die from pulmonary complications.
Already, Zahra’s respiratory muscles are wearing away, her parents say, making a minor cold or cough a dangerous medical event as coughing is difficult for her.
Though her body is deteriorating, cognitively Zahra shines, her parents say. She loves homework. She can memorize a mobile-phone number after hearing it twice. She likes to count backward from 100 and can multiply two-digit numbers. At school, her classmates play hide and seek during recess and she watches. “She doesn’t show that she is envious of them,” Mrs. Zareinezhad says.
Gholamreza Zamani, the pediatric neurologist at Children’s Hospital Medical Center in Tehran who treats Zahra, says Spinraza’s effectiveness depends on when it’s started. Though not a cure, “this drug can affect her quality of life and prevent more regression in her motor function,” he says. So much scientific effort and money goes into making such treatments, says Dr. Zamani, but “if the patient who needs it can’t access it, what’s the purpose?”
Until recently, SMA had no treatment. In December 2016 the U.S. Food and Drug Administration approved nusinersen, sold under the brand name Spinraza. It is injected into the spinal fluid through a spinal tap.
In a clinical trial, Spinraza was found to be effective in up to 51% of patients with type 1, significantly slowing the disease’s progression, in addition to improving their strength and lifespan. A clinical trial published in NEJM last year showed for type 2 patients like Zahra there were improvements in motor function and upper limb function after 15 months but the improvements weren’t dramatic as those seen in type 1 patients. One patient regained the ability to walk with assistance.
Zahra’s family submitted a request to Biogen for a discount or compassionate use of Spinraza in October. A spokesman for Biogen said via email that the company has been in communication with the family and “will provide them an update once there is a development on registration,” a first step in getting the drug approved for use in Iran. In January, Biogen said company representatives “were in Iran this month for meetings with the government and continue to work on registration.”
“We recognize the gravity of this situation and considerable work has been under way the past few weeks,” the Biogen spokesman said. “The complicating factor in Zahra’s case is her location in Iran. We are working with the Iranian Minister of Health on the first step of registration.”
Mahdi Shadnoush, an Iranian health-ministry official who said he’s not familiar with Zahra’s specific case, said that even if the drug were approved for import, U.S. sanctions present a hurdle because global banks are reluctant to arrange a transaction with Iran. U.S. rules exempt medical goods from sanctions, but many banks still hesitate to arrange trade deals with Iran after having incurred fines during previous rounds of sanctions.
Mr. Shadnoush says there are at least 600 cases of SMA in Iran.
Zahra’s parents say they would travel to a country where Spinraza is approved, such as Germany or Turkey, if they could raise enough money to buy the drug there. (A Biogen spokesman says the treatment is available in more than 40 countries and the company is seeking to make the treatment available in more.) The family raised some funds but a crash in the value of the Iranian rial slashed that amount.
Zahra’s family has an attorney friend in the U.S. who hopes to raise money from U.S. donors, but sanctions complicate those efforts. U.S. restrictions dating back to 2013 require nongovernmental organizations making donations to Iran to follow parameters laid out in a general license, and cap donations at $500,000 a year unless an additional license is granted, a U.S. Treasury spokesman said. Personal, noncommercial remittances to Iran or Iranian residents in other countries are generally allowed but money raised to pay for a medical treatment might require a specific license, the spokesman added.
Biogen has programs that provide discounted or free access to drugs for patients who meet certain criteria, but that path is complicated too. Zahra isn’t eligible for one of the main programs because only patients with type 1 qualify, which would be the case even if she were in the U.S.
Zahra’s family tries to take pleasure in simple things. They help her on the slide in the playground. They take her to the countryside twice a year because she loves to go on trips.
“She really hopes that the treatment will make her a normal child and plans a normal future for her,” Mrs. Zareinezhad says. “She has chosen her bicycle, future car, job. But right now, time is critical for us and we should be able to access Spinraza as soon as possible to slow down the progression.”
Treatments on the Horizon
Other companies are working on treatments for spinal muscular atrophy. Roche and Novartis are developing oral medications similar to Spinraza, says Richard Finkel, chief of the neurology division at Nemours Children’s Hospital in Orlando, Fla., who is a paid consultant and working on clinical trials for all the biotech companies working on SMA treatments.
Further along is a gene-therapy treatment from AveXis, a Novartis company, called AVXS-101, currently before the FDA. Federal regulators are expected to make a decision by May but the therapy would likely be initially for type 1 patients only. The company has also applied to regulatory agencies in Japan and the European Union for approval.
Write to Sumathi Reddy at firstname.lastname@example.org