by Geeta Anand
The idea came up that it would make a wonderful book. In January 2004, I began reporting and writing this book, and I spent the next two and a half years interviewing the Crowleys, their friends and family, and almost everyone trying to develop a treatment for Pompe. My daughters, Tatyana and Aleka, both in elementary school at the time, accompanied me often, playing with the Crowley kids while I talked to their parents.
One side benefit of the Crowleys’ huge house is that even in her wheelchair Megan was actually able to find places to hide during her games of hide-and-seek. “Megan is so cool,” Tatyana said on the train home after a marathon game. Indeed, on that day Megan made using a wheelchair look like so much fun that, as Tatyana reached the top of the steep flight of stairs leading to our apartment, she turned around and asked, “If I fall down there and break my leg, can I get a wheelchair like Megan’s?”
So much has happened since that summer afternoon in 2003, where the book ends, that I could easily fill a sequel—and maybe someday I will. But in the meantime, here’s a synopsis of the intervening years. They are, like this book, about the pace of biological discovery and the power of the profit motive to speed science into medicine, but equally—if not more—important, about the resilience of hope and the enduring force of parental love.
For the first six months after receiving their Special Medicine in January 2003, Megan and Patrick continued to grow stronger. But toward the end of the year the gains slowed, and by early 2004 John and Aileen noticed a slight decline in the children’s skeletal muscle strength. When Megan stopped too abruptly, her head once again fell forward. She needed to use her hands to push her head back up. Patrick began to struggle again to grip his favorite Power Ranger figures to make them fight one another.
“Why aren’t you getting stronger?” John found himself thinking, frustrated.
Then he would remind himself that his children’s hearts, so swollen before treatment that they had posed the biggest risk to his children’s survival, remained substantially stronger. Perhaps the drug had done all that it was meant to do: it had bought the children time.
With his well-known success in building and selling Novazyme, John was eagerly recruited by biotech and venture firms in the months after leaving Genzyme. He thought about retiring on his $6 million, but it wasn’t in his nature to throw in the towel at the age of thirty-six. Besides, he had the children’s future health-care costs to think of.
John’s Novazyme and Genzyme experiences made him the go-to guy for anyone with a potential treatment for Pompe. Even as he ran the two start-ups, he was in Florida one week, checking out Dr. Byrne’s gene therapy; Utah the next, interrogating scientists about stem cell therapy; and Milwaukee at the end of the month, investigating an idea for improving enzyme replacement therapy.
Before long, John was on the boards of seven fledgling companies, five of them developing treatments for genetic diseases like Pompe. In the spring of 2004, the investors at one, Amicus Therapeutics in New Jersey, asked him to take over as CEO. John demurred, unwilling to back just one horse when he wasn’t sure which one had the potential to win. There was too much at stake, and “emotionally,” as he told me, he was “not quite ready to get back into genetic diseases and Pompe every day.” But he did agree to consult for Amicus one day a week to develop a strategic plan and lead the search to find a CEO.
The more John learned about Amicus’s science, the more excited he became about its potential to help his children. As he knew already, most patients with Pompe don’t entirely lack the acid alpha-glucosidase enzyme; rather, they make it incorrectly, so that the body misidentifies and eventually discards it. Instead of trying to find a way to replace this enzyme, as Dr. Canfield had been, Amicus’s founding scientists tried using chemicals that stabilized the acid alpha-glucosidase enzyme so that it wouldn’t be identified as errant and then degraded. Scientists call these chemicals “pharmacologic chaperones,” because they bind to the defective enzymes, enabling them to survive and travel to the region of the cell where they are needed.
About 80 percent of Pompe patients, including Megan and Patrick, have imperfectly produced acid alpha-glucosidase enzyme. Most human genetic diseases involve similarly defective proteins.
In October 2004, John led a strategic planning session for the Amicus board in which they discussed the potential of pharmacologic chaperones to treat not only genetic diseases but many other disorders like Parkinson’s and Alzheimer’s. When the board again asked John to consider taking over as CEO, he couldn’t turn it down.
“I still really don’t want to have to do this,” John told me at the time. “But I think I have to. This technology could save the kids.”
When John informed Aileen he wanted to take the Amicus job, he told me, she took a deep breath, grew tearful, and said, “Here we go again. You know I’ll support you in anything that could help the kids.”
John phoned Henri Termeer, Genzyme’s CEO, wanting to be the first to tell him he would be heading a company with a competing technology. The older man surprised him. “I hear you’re going to take the job after all,”1 Henri said with a chuckle when he came on the line, beating John to the punch line.
“Word sure gets to you fast, Henri,” John replied, rueful and amused.
Henri wished him well.
When John took over as CEO of Amicus on January 3, 2005, the company was already fairly well funded. It had $15 million in the bank, even though there were only eight employees. Just as he had done at Novazyme, John hired the consulting firm Health Advances to help write a business plan.
In his nearly five years so far at Amicus, John has raised more than $300 million for the company, including $75 million in one of the most successful IPOs in the biotech industry. While Amicus has made great strides, it hasn’t been an easy road. As happens often in drug development, some of Amicus’s clinical trials have failed. One trial of a potential new Pompe drug was stopped because the patients became weaker and more tired; it is back in testing as of fall 2009. In another blow, patients with Gaucher disease didn’t seem to benefit in a small trial of another potential new Amicus drug.
It turns out, however, that the Amicus therapy might help improve the efficacy of the treatment Megan and Patrick and hundreds of Pompe patients continue to receive: the Genzyme enzyme replacement therapy called Myozyme. It is too early to know for sure, but John says that in animal testing, an Amicus drug helped stabilize Myozyme and improve its absorption.
Though John finds the job exhausting, it has also been therapeutic for him, helping him contain the frustration—and fear—he feels from his children’s slowly declining strength. The knowledge that he’s doing everything he can to find a treatment to make them stronger allows him to relax enough to enjoy his time with them and let go of his fear of losing them.
“There are two differences from last time around,” John told me. “I think this time, I actually know what I’m doing, from people to science to finance. I haven’t screwed this one up,” he added with a self-effacing laugh.
“It’s been stressful, but for general business reasons. Because of Megan and Patrick, there’s a sense of urgency behind it, but I have a little different perspective. I realize the battle against Pompe is really a marathon and not a sprint. If you make it a sprint, you make mistakes and you burn out yourself and your team. I still set aggressive goals, and nobody in this company ever worked harder, but not in the exhaustive sense that the kids are going to die tomorrow if we don’t do it. It helps that the kids have been relatively stable for the past two or three years. I also appreciate just how complex this disease is.”
Sharon still lives with the Crowleys during the week and commutes home to her husband and extended family in New England on most weekends. She is now more than sixty years old, and it’s becoming harder for her to lift Megan and Patrick as they keep growing, but she continues to be a loving caregiver and a part of the family. For a time she hired Mr. Hennessey, Megan’s P.E. teacher, as her personal tr
ainer two afternoons a week. She and the other nurses work overtime on occasional weekends to allow John and Aileen to get away together.
For their fifteenth wedding anniversary, Aileen joined John on a business trip to France, and they spent several days afterward touring Normandy.
“If you knew when we met what you know now—that all of this would happen to us—would you have still married me?” John asked Aileen one evening as they were falling asleep in their hotel room.
“Yes,” Aileen said without missing a beat. “How about you?”
John was silent for a few seconds, and then replied, “Yes, Aileen, I would, too. I wouldn’t give up these kids and this life with you for anything.”
While they have come to accept that this disease may define the rest of their lives, they are content to find joy where it comes to them: in the long weekends away that Sharon’s kindness allows them to take; in their children’s enjoyment of each day; in the continued celebration of birthdays and holidays and the forward motion of their lives.
In spring 2006, Genzyme received approval from both the FDA and European regulatory authorities to market Myozyme, the Pompe therapy that Megan and Patrick continue to receive every two weeks.
“This is a very special day for people across the Pompe community and at Genzyme who have worked together for many years and overcome enormous challenges so that patients with this devastating disease now have a chance,” Henri Termeer said, in announcing U.S. approval of the drug.
Genzyme reports spending more than $500 million since 1998 in the development of the treatment, which is priced in the same range as the company’s other genetic disease therapies: about $200,000 for the average patient annually.
Reporting on the trial in older babies and toddlers, Dr. Priya Kishnani of Duke University said that sixteen of the twenty-one (more patients were enrolled than planned) were still alive after a year of therapy. Ten had gained so much strength that they could perform new motor functions—such as holding up their heads, sitting, and even walking. Eleven were still able to breathe independently.2
Even in the trial results, however, it was clear that Megan and Patrick are not unique. Eleven children did not gain sufficient strength to perform new motor functions; five children died, and five who could breathe on their own at the start of the trial needed ventilators before the year was over. The results also show “that early initiation of [therapy] is of paramount importance in maximizing the chances of a favorable motor outcome,” Dr. Kishnani wrote. Her results underscore what John and Aileen already know—that it is likely that Megan and Patrick would have gained much more strength on Myozyme had they been treated when they were younger and stronger.
Dr. Canfield remains a scientist at Genzyme, running the Glycobiology Research Institute, the name given to the former Novazyme business. Hung Do, before moving to Amicus, worked with Canfield and others at Genzyme to develop what they believe is a better version of Myozyme. The results of the experiments they conducted may eventually vindicate Canfield’s beliefs about the importance of having the right carbohydrate chains—in this case, mannose-6 phosphate—attached to the enzyme for it to be taken into the lysosomes of muscle cells.
The problem with Dr. Canfield’s earlier version of the enzyme, scientists at Genzyme now believe, was that other sugars attached drew it elsewhere before it could get to the muscle cell lysosomes. Besides avoiding that pitfall, the new enzyme is easier to produce. The carbohydrate chains are chemically fused onto Myozyme. In mouse experiments, the new version appears to be absorbed three to five times better.3
Genzyme scientists say this is one of several new approaches that may evolve into a better second-generation treatment.
Tiffany House, who grew weaker when she was first moved off the Pharming enzyme and her dose was decreased, is feeling stronger on a higher dose of Myozyme.4 She graduated in 2005 with honors from the University of Texas in San Antonio and enrolled in a master’s program in English. She’s still in a wheelchair and needs breathing support at night, but she’s becoming more independent. When I last spoke to her in the spring of 2006, she hoped that she would eventually gain enough strength to go to law school.
Lindsey Easton, still only able to move her eyes, mouth, and thumbs, graduated in 2005 as co-valedictorian from Glenpool High School. Her speech, read aloud by her grandfather, brought the audience of students and their families to their feet. “Physically I am weak, but I have met that challenge by utilizing my strength—my mind. I have experienced numerous adventures through reading that I cannot enjoy physically. When you meet a roadblock, don’t give up, look for alternatives or solutions to those dead ends.”
When I last spoke to Lindsay’s mother, she said Lindsey was taking classes online at the local community college. Lindsey hadn’t received the Genzyme treatment yet, but she was hoping to begin therapy soon, even though she was uncertain how much of her lost muscle strength the medicine could restore.
True to his word, John did ensure that Megan Assink was one of the first patients to be treated in Dr. Byrne’s trial for older babies and toddlers. At the time she was treated, in spring 2003, she was one and a half years old, still able to sit and eat but losing strength. Just like her namesake, Megan Crowley, and her late sister, Kelsey, she couldn’t crawl and her tongue protruded slightly.
Today, at age eight, Megan Assink is in second grade at Georgetown Elementary School in Hudsonville, Michigan. She still receives Myozyme regularly and looks almost like any other kid. Her tongue doesn’t protrude and she can smile. With braces on her legs, she can walk. Her speech is difficult to understand when she talks fast, so she uses a talking computer to help her communicate.
“She’s a miracle child,” Greg, her dad, says. “I will never be able to thank John enough for making this happen.” Greg and Deborah sent John a thank-you card a few years ago with a tape of their daughter walking. After watching it, Megan Crowley wheeled up to her father. “That’s great,” she said flippantly, “but why aren’t I walking?”
Before John could think of the right answer, Megan sped away, heading for the toy room. As always, she didn’t pause for long to think about her disability.
Megan Crowley is now in seventh grade at John Witherspoon Middle School, a public school in Princeton. When she graduated last year from elementary school, she wheeled herself up to the microphone and, like the rest of her classmates, gave a short speech. “Thank you all of my teachers and all of my nurses who have helped me along the way,” she said. Then she pulled her chair back to allow her best friend, Julia, to repeat what she had just said so the audience would understand. Though Megan’s speech was not much different from her classmates’, it was greeted with cheers from an audience who recognized what a miracle it was for this little girl to graduate from elementary school.
With her thirteenth birthday fast approaching in December, Megan is thinking ahead to her sweet sixteen party. Like Aileen, she likes nothing better than planning a party. John told her she couldn’t start planning her sixteenth birthday until she was thirteen—and she took him quite literally. Like her dad, she thinks big. Having recently attended a “Make a Wish” bash at the Hyatt Hotel in Jersey City, which overlooks Lower Manhattan, she’s been telling everyone lately that that’s where she’s decided to hold her own landmark birthday.
Patrick is now in sixth grade, also at John Witherspoon. Aileen accompanies him to school two or three days a week, with a nurse filling in the rest of the time. (Sharon remains Megan’s nurse most days at school; both kids still need trained nurses with them at all times to manage their ventilators.) Over the years, Patrick has grown happier and more communicative, with the help of a talking computer. At his elementary school graduation in June 2009, he used the computer to give a speech of his own, in which he gave a special thank-you to the teacher of his favorite class: gym.
“You know, the kids aren’t walking, but they sure as hell couldn’t be happier,” John says often.
John Jr. is
in eighth grade in a special education program at the same middle school. He still struggles with hyperactivity and dyslexia. This year, during a meeting with school officials and his parents to discuss his education plan, Aileen asked her son if he still needed an aide to help him in school.
“No, I can do it myself,” John Jr. replied.
Aileen and John decided to give John Jr. a chance to be independent in school. To everyone’s surprise, he’s managed to get to all of his classes. “We just got his report card and he’s gotten awesome marks,” his dad exuded in a recent conversation.
The highlight of this year for the entire family was their trip to Portland, Oregon, to watch the filming of the movie Extraordinary Measures, which is inspired by this book and their story. John flew the extended family to Oregon—including the kids, Aileen’s parents, his own parents, Sharon, and two other nurses.
The Crowley clan arrived on the set in April as the actors were shooting a scene in which Aileen—played by Keri Russell—is loading her three children into a handicapped van. After about a half hour of filming, the assistant director, with great fanfare, announced that there were some special guests on the set that day.
“Everyone, can I have your attention, please? I’d like to introduce to you the real Megan, Patrick, and John Crowley.”
Megan, holding the hand of the young actress playing her, wheeled herself around the set.
The Crowleys chatted excitedly with Harrison Ford, who plays a scientist, and Brendan Fraser, starring as John. “But for us the most special moment was meeting the three kids playing our kids,” John says.
As John has thrown himself back into the race for a cure, Aileen has stuck by her mission—to keep the kids happy. And certainly their wealth has helped. Almost every year, the Crowleys have hosted annual Halloween parties at their house, inviting several hundred guests, including friends from high school and college, extended family, and also the children’s nurses, therapists, teachers, and doctors, as well as Novazyme alumni and Amicus employees. There are always JELL-O shots, a DJ, and a dance floor. And almost always, John and Aileen, along with Sharon and her husband, Eddie, have been the last ones shimmying on the back deck under the floodlights.
