A drug pushed back the missing bones of a little girl. How much should it cost?
Evie Elsaesser is five years old and she loves to run. And it is a medical miracle.
When Evie was born, much of her skeleton was left soft and uncalcified. His arms were short, his ribs tiny, and his legs arched. They curled up under her like she was doing yoga.
Her mother, Lindsey, had only expected to know her daughter for a few hours. On a 12-week ultrasound, Evie’s arms, legs, and nose bones were so weak that a doctor missed them. Doctors believed she suffered from osteogenesis imperfecta, a fatal disease. The diagnosis was wrong. After the birth, a brain ultrasound and x-rays suggested she might survive – and she did. But the doctors had no idea what was wrong with her.
After two weeks the seizures started: Evie would stop breathing for a few minutes. Her parents rushed her to the hospital, where a series of blood tests ultimately led to a diagnosis. Evie’s levels of alkaline phosphatase, a chemical important for hardening bones, were low. This meant that she was suffering from an incredibly rare genetic condition called hypophosphatasia (PPH). The severe form affects 1 in 100,000 newborns.
The geneticist would later tell Lindsey that he expected Evie to die within five months. Doctors could give him medicine to relieve the seizures, but there was no treatment for his fragile skeleton. But then she was signed up for a clinical trial for asfotase alfa, a drug developed by Enobia Pharmaceuticals, a Montreal-based biotech startup with just two dozen employees. The drug replaced the missing bone-forming enzyme.
Evie began injecting asfotase alfa three times a week when she was three months old. It got worse before it got better. She needed oxygen and when she was five months old she contracted respiratory syncytial virus (RSV), which made her even sicker.
Then Lindsey started to notice that her daughter’s muscles seemed stronger. During the baby’s regular x-rays, she looked behind the technician. At first, Evie’s bones had looked translucent and gray, but they started to harden. “Every little streak of white we saw on the bones was good,” says Lindsey.
Evie put out a special low calcium infant formula. She needed constant oxygen, which meant she was learning sign language instead of speaking. But after seventeen months, she could breathe on her own. She learned to walk with a walker and went to kindergarten.
As she grew stronger, she learned to stand and walk unaided. She has learned to speak – “she talks a lot,” says Lindsey – although her missing front teeth (a consequence of PPH) can make her difficult to understand. She needed surgeries to undo the fusion of the bones in her head and to loosen the tendons in her legs which made her twisted. But with straighter feet, she runs. Lindsey sent me videos of Evie running 25 and 50 yards – and laughing happily.
“We saw babies being saved from what we thought was a high probability of death,” says Dr. Michael Whyte, bone researcher at Shriners Hospitals for Children in St. Louis who led some of the asfotase studies. alfa. “We find that they appear to be perfectly healthy children and the parents appear to be the same.”
Data presented last month at the American Society of Bone and Mineral Research annual meeting last month showed that over five years, 33 out of 37 (89%) PPH patients who received asfotase survived. , compared to 13 out of 48 (33%) in a comparable historical group. This included 11 of 13 patients who, like Evie, had seizures, compared to 0 in 10 in the historical control.
Thanks to an experimental drug, a little girl who would almost certainly have died runs and laughs. This is exactly what we hope the new drugs will do: make a real difference in lives. Now for the question that determines how many of these drugs we get: society, what is that worth to you?
Evie’s medication will likely cost over $ 200,000 per patient per year. In 2012, Enobia was acquired by Alexion Pharmaceuticals of Cheshire Conn. Alexion already sells one of the most expensive drugs in the world, Soliris, to treat two different conditions: paroxysmal nocturnal hemoglobinuria (PNH), in which the body destroys its own red blood cells. ; and atypical hemolytic uremic syndrome, in which the immune system destroys the kidneys. In the first year, a large initial dose of Soliris is given, which slightly increases the cost. But after that, the wholesale cost of one year of treatment for a patient is $ 469,363 for PNH and $ 625,817 per year for aHUS, which requires higher doses of Soliris.
Soliris is not the only or even the first drug of this type; today there are at least a dozen drugs that cost more than $ 200,000 per patient per year, and their number continues to grow. Pharmaceutical companies first became interested in rare diseases in 1983, when a law, the Orphan Medicines Act, granted companies that had obtained approval for diseases affecting fewer than 200,000 people additional protection against them. competition. But the really high prices started in 1991 when a biotechnology company in Cambridge, Mass., Genzyme launched a drug called Ceredase for Gaucher disease, which causes fat to build up in bones, muscles, and heart. and even the brain. Only 5,000 people have it.
Ceredase was painstakingly made from human placentas and cost $ 150,000 per patient per year. But when Genzyme found an easier way to produce it in genetically engineered hamster ovary cells, the price actually went up. It can now cost $ 300,000 per patient per year, and Genzyme now sells five products at similar prices. Genzyme was acquired by French pharmaceutical giant Sanofi for $ 20 billion in 2011.
Other companies have followed Genzyme’s path. Shire, the Irish pharmaceutical company bought by AbbVie for $ 54 billion, has bought out one of Genzyme’s earliest competitors and has developed a large business in so-called ultra-orphan drugs. In recent years, high-priced drugs have been introduced for genetically very high cholesterol, short bowel syndrome, and cystic fibrosis.
However, few have been as successful as Soliris. Sales totaled $ 1.5 billion last year, and analysts at Piper Jaffray, an investment bank, predict they will reach $ 5.5 billion by 2020. That same year, Piper Jaffray expects asfotase alfa sales of $ 900 million.
To some, this may sound like a highway robbery on Bell’s part. But in past conversations, he’s given me a very different perspective. The high costs of these drugs are necessary to convince companies to undertake the decades-long task of bringing them to market, and the drugs are worth it because they save lives in ways that most drugs do. just not. They represent the will of society to treat those in need, no matter what.
The National Institute for Clinical Evaluation (NICE) in the UK is widely regarded as one of the toughest negotiators in the world when it comes to high drug prices. Yet after initially refusing, he agreed to pay for Soliris, as well as Kalydeco, the breakthrough cystic fibrosis drug developed by Vertex Pharmaceuticals. (UK gets a list price discount; so does Medicaid, but there is little price transparency.) There is no doubt that some drugs are worth these sky-high prices.
Another thing Alexion inherited from Genzyme is a core system where the drug company works to make sure patients don’t go without drugs. When the full price cannot be paid, they donate the drug or, in cases where it would be seen as a bribe, they donate money to charities that make the difference between what a insurer will cover. On Wall Street, this idea has become a philosophy, even when it is not applied to new drugs, but to the increase in the price of old ones.
In September, a small biotech called Retrophin bought a drug for a rare kidney disease called cystinuria and increased the price from $ 1.50 per pill to $ 30 per pill. The chief executive of the company, a 31-year-old investor named Martin Shkreli, argued that the higher price would lead to better access for patients and no one would be turned away. “No patient will be left behind, on my corpse,” Shkreli wrote on Reddit as he defended the decision. “No one will be forced to pay exorbitant amounts for their drugs. We give you the medication and determine it with your insurer.
Shkreli may have been too frank. For various reasons, including Shkreli having inappropriately granted stock options, his board of directors rebelled and he left the company shortly thereafter. But he still speaks for the many investors who have internalized the idea that high drug prices can be a merciful boon, a financial instrument that can be used to help people who are incredibly sick in a free market system, with the company as a whole invoices. But it is also fair that the company questions whether it is paying too much. The list price for treating a patient with PNH has increased by $ 70,000 since Alexion launched Soliris; without knowing what insurers and governments are actually paying, it’s hard to know if this price increase is a good deal.
Ultimately, none of this matters to a parent who just wants to watch their child grow up. I pushed Lindsey Elsaesser forcefully on what she thought of the likely costs of the drug her daughter was receiving – so hard that she was upset and apologized when the conversation was over. But it wasn’t something she seemed to have thought about.
“It’s really up to Alexion,” Lindsey told me. “They’ve been so gracious to everything so far, I guess we’ll find out when we get there. Really, I would do anything so she could have it.