by Geeta Anand
“Hey, Mario Andretti, slow down,” he said, jumping backward. Like the average five-year-old, she moved quickly when excited. Her electric wheelchair was big and black with a head support, a foot rest, and a pocket for her ventilator in the back. A seat belt kept her from falling out. She had grown so comfortable in the chair that it really had become an extension of her body. She could amble, speed, twist, and twirl in that chair.
“Megan, I have the best news for you,” John said, the words bursting out. “Special Medicine is ready.”
“Where is it?” she asked, backing up.
“It’s in Cambridge, Massachusetts, where Daddy goes every week.”
Megan considered. “Is it pink?”
“We’ll have to see. I’ve told them in Cambridge that you want it to be pink and they’re working on it.”
“Who else is going to get it?” she wanted to know, mouthing and signing questions so fast now that he could barely keep up.
“You and Patrick.”
“Hurray,” she sang, pumping her arms.
Megan sped around John in circles, singing, “I’m getting Special Medicine.” After a half-dozen circles, she zoomed toward the kitchen where her mother was reading to Patrick.
“John, tell Patrick,” Aileen said. John bounded to Patrick’s side and relayed the same news. Patrick waved his hands and squeaked as he always did when he saw his father. John was never sure how much his youngest child understood. He bent and kissed him on the forehead, content in his joy to take any reaction Patrick had.
John thought it should have taken Landy a couple of days to write the protocol—the detailed plan for conducting the clinical trial. But days flew by, then weeks. He wanted to order Landy and his team of clinical research assistants to work faster, but he felt he couldn’t because they didn’t report to him. Each time he inquired—and he did, every few days—they made clear they were swamped by work that was a higher priority. And from a corporate point of view, John couldn’t deny that the two main trials that would form the basis of Genzyme’s application for FDA approval ought to be a higher priority. As head of the Pompe program, how could he argue that his children’s trial was more important than the trials on which a new treatment for all patients rested?
After an excruciating month, Landy’s team finally submitted his children’s trial protocol to CHOP. Now John waited for the hospital’s clinical trial review board to meet and assess the protocol. Several more weeks went by. Finally, the board was set to meet in early August, two days into the summer vacation John and Aileen had planned with the family in Ocean City, New Jersey.
Before John left, he made arrangements with Dr. Richard Finkel of CHOP to relay the board’s decision to him while he was in Ocean City. The famous neurologist was to lead his children’s Sibling Study and had promised to call.
Aileen drove down first in the morning to buy food and set up the oceanfront house they had rented for two weeks. Anticipating the horde of relatives and flood of medical equipment that had to come with them, they’d gotten a six-bedroom house with an elevator and a four-car garage. John followed in the afternoon at the wheel of the handicapped van carrying Megan, Patrick, John Jr., Sharon, and all their medical supplies. It had taken a week of planning and three hours of loading to get the van ready with everything needed for the fortnight.
Aileen had chosen Ocean City, thinking that it would be easy for Megan and Patrick to ride in their wheelchairs along its big wide boardwalk lined with stores, restaurants, and a park featuring dozens of rides. But it was too hot the afternoon they arrived to take the children outside. Patrick watched television, and John and Aileen played a series of board games—Arthur’s Library, The Princess Game, and checkers—with Megan and John Jr.
Soon the guests were arriving. Sharon’s daughter Misty and three grandchildren had followed John’s van. Aileen’s parents came next, followed by her brother Brian, his wife Kim, and their three children. In addition to Sharon, two other nurses were there to share the round-the-clock care of the children. Altogether, there were nine kids and nine adults in the house, making it crowded despite the three floors.
When the temperature finally fell in the early evening, everyone spilled onto the boardwalk, heading for the rides. Megan led the way in her electric wheelchair, the other kids struggling to keep up on foot. Aileen pushed Patrick, talking excitedly about the rides. Megan declared the Ferris wheel was going to be the first stop.
“Aileen, tell her that nobody’s going on the Ferris wheel,” John said, pleading. “There are plenty of other fun rides that are safer.”
Aileen, shaking her head, said, “John, I’ve promised the kids they can go on the Ferris wheel. We have to let them have fun.”
The group reached the entry to the Ferris wheel and discovered two steep flights of steps leading to the launching area. John’s eyes widened and he shuddered involuntarily. Aileen ignored him and carried Patrick up the stairs, Sharon following with his ventilator, Aileen’s mother standing at the entrance guarding the wheelchair. Sighing, John followed with Megan in his arms, Aileen’s brother Brian carrying the ventilator, and her father remaining beside the little girl’s wheelchair.
In no time, they were flying high above the beach, Aileen and Patrick in the cart above John and Megan. Aileen peeked over the edge and saw John holding fast to Megan, his eyes shut. She burst out in giggles, suddenly remembering that years ago, before they were married, John had thrown up on a roller coaster, splattering the other passengers. John’s reluctance to let the family get on the Ferris wheel hadn’t been for the kids’ sake—he was scared of heights. Megan looked up, saw her mother, and waved, running her finger over her cheekbone. When Megan was learning sign language years ago, Patrick had been fed through a tube in his nose, so Megan’s sign for him, to distinguish him from everyone else, was to trace the path of the tube across the side of his face. Aileen leaned Patrick’s head over in Megan’s direction so they could see each other. As Megan waved, Patrick flapped his hands excitedly.
When the Ferris wheel finally came to a halt, John got off, mumbling, “I’m not getting on another ride.” But minutes later, he was rolling down the tracks beside Megan on the train ride, Aileen and Patrick in the cart behind them. The vacation was off to a great start.
It was 9 P.M. when the group finally headed home on the boardwalk, Megan again in the lead. Somehow, her wheelchair got locked in an upright position. Each time she went over a bump, her head fell forward. John, walking beside her, had to lift her head back up.
“Megan, what are you doing?” he said, after several lifts.
“She can’t do it by herself anymore,” Aileen whispered, shushing him.
The information hit him like a big wave, knocking him out of vacation mode. He knew neither child could sit up anymore, not even with assistance. But he hadn’t noticed that Megan had gotten so weak she could no longer pull her head up if it fell forward. Thank God she was going to be treated any day. As he patiently pulled Megan’s head back up again and again, he thought of Dr. Finkel, who was supposed to call the next day to report on the board meeting. John silently prayed that there wouldn’t be any further delays.
All day Monday, John played checkers with Megan and John Jr., while listening for Dr. Finkel’s call. It was too hot again to take the youngest two outside, but John took a drive with little John to the liquor store to buy a bottle of his favorite Veuve Cliquot champagne, anticipating that at long last there would be some good news.
The next morning, after Aileen left for the beach, John dialed Finkel. The doctor took the phone, apologizing for not calling the previous day. He didn’t have good news and hadn’t wanted to ruin John’s vacation. “There’s some concern on the IRB about the ethical fairness of treating your kids. There’s a concern about a conflict of interest.”4
The thought that the hospital might actually turn down the trial had simply not occurred to John.
“Dr. Finkel, Megan and Patrick will be the twenty-sixth
and twenty-seventh kids who will have received a Genzyme Pompe enzyme,” he said, desperately. He knew to the digit the exact number of patients in the United States and Europe who had already received Chen’s or Pharming’s enzyme either in trials or with special permission from government agencies and Genzyme, known as compassionate use.
Finkel tried to reassure John. He said he had talked to the head of the review board, and he thought he could get the trial approved after making a few changes and resubmitting it for the September meeting.
Aileen came back from the beach and immediately asked John if the doctor had called. John took her into their bedroom and told her about the conversation.
“I’m not surprised,” Aileen said bluntly. Without asking another question, she left the room and went downstairs, plunging herself into conversation with the other guests.
For the rest of the week, the house was packed with friends and relatives. They sat on the patio, drinking and talking late into the night. John found it hard to join in the fun. He wanted a quiet place to read and rest, and there was none. His head hurt, and his heart was heavy with disappointment. One night, as he lay in bed trying to sleep, the group on the patio was exceptionally loud. He couldn’t escape the booming voice of Aileen’s brother Marty, who had arrived that day. Frustrated, he walked out onto the patio and asked the group to lower their voices.
“Shut up,” they yelled back tipsily. Several bottles of wine sat on the patio table, uncorked.
Aileen, who had been telling John all week to relax, let loose, and have some fun, flapped her hand at him and continued, “Get out of here, asshole.”
When Aileen awoke the next morning, John exploded at her. “I rented this house and all of these people came down here,” he shouted, so loudly that she pulled him into the bathroom to keep the others from overhearing.
“But you invited them,” she said in a loud whisper. “You’re waking everyone up.” He was too upset to care.
John’s relationship with his guests went from bad to worse. His mother arrived later that morning and gaily suggested they take a day trip. “How about we head up the road to Atlantic City and do a little gambling,” she said. When he shook his head, she teased him, saying “Don’t be an old fart.” John bellowed in response, accusing her of not visiting her grandchildren enough. Soon they were yelling at each other and bringing up everything that had annoyed them in the past few years. She said she didn’t feel comfortable in his house now that he was a rich big shot.
“Then leave—get out!” he said, unconsciously echoing his wife’s words from the night before.
She drove off.
John woke up early the next morning, pulled on shorts and a tank top, and went for a run down the boardwalk. He felt lethargic and out of shape. Until a couple of years ago, he had run and lifted weights almost every day. Now the constant travel had thrown off his schedule; he rarely exercised these days, and he had several extra pounds around his middle. As he built up a sweat, he thought about how he was close to the emotional low of three years earlier, when the only road to happiness had seemed to be to divorce Aileen and live across the street. He reminded himself that his frustration was not Aileen’s fault, not his mother’s, not Marty’s, and certainly not the children’s. He was just tired—tired of living away from home, tired of trying to be the objective head of Pompe disease, tired of being on a quest to save his children that never seemed to end. He simply didn’t want to do it anymore.
As the sun rose, he stopped and walked, breaking hard. He had been mulling for a long time whether to stay on at Genzyme, which meant moving his family to Boston, or whether he should quit after his children got treated. With his mind cleared from the exercise and the quiet of the predawn morning, it became clear to him that he should leave. As part of the sale to Genzyme, he had agreed to stay at the company for one year. Next month, that year would be up. When he returned to Cambridge, he decided, he would quietly tell van Heek that he planned to resign at the end of the year. That would give him enough time to get his kids treated and submit plans for the two main clinical trials to the FDA. All he had to do was get over the worst vacation of his life and hang on a little longer at Genzyme—just long enough to let Finkel work out the kinks in the Sibling Study at CHOP.
But two weeks later, Landy, who had sympathetically told John to let him handle communication with the Children’s Hospital, was back on the phone with more bad news. A hospital board had met again, and still had not approved the Sibling Study. There were still too many questions about conflict of interest, Landy said. “You might want to have a Plan B.”
“A Plan B,” John said blankly. “Right. Yes, yes, we’ll find a Plan B.” He put the phone back into the cradle, gently, and lowered his head into his hands. He couldn’t even summon the energy to be angry or disappointed. He’d been coming up with Plan Bs for four years now. It was probably time to just give up.
25
Plan B
Fall 2002
Princeton, New Jersey; Rotterdam, Netherlands;
Gainesville, Florida
A week later, John called Dr. Byrne, the University of Florida physician-researcher who had performed the laboratory experiment that appeared to show that Canfield’s enzyme made mice stronger. Byrne had cowritten the plans for the animal studies and human clinical trial for Novazyme. As the doctor who would have been in charge of the Novazyme clinical trial, he had taken the design to his hospital’s clinical trial review board a year ago and gotten approval.
John told Byrne his children were declining fast. “Megan can’t even pull her head up if it falls forward. I know it sounds like a little thing, but it’s that final piece of dignity. And Patrick’s even weaker.” John described plans for the Sibling Study and how they had been repeatedly turned down by the Children’s Hospital of Philadelphia.
“I was wondering if we could do the Sibling Study at your hospital, Barry?”
“I’d love to help,” Byrne said sincerely. “The geography’s not the best, though,” he said.
“Right now I’d go to the moon to get Megan and Patrick treated, so Florida is not that far away,” John said, wearily. “You’re right, Barry, the geography is not ideal. That’s why I didn’t think of you in the first place. But with all the trouble at CHOP, I’d just like to move this along quickly. I don’t think the children can hang on much longer.”
Byrne asked John to e-mail the Sibling Study protocol, and said he would use it to write an application to his hospital’s clinical trial review board, which would meet again in October. He promised to call as soon as he had news.
John asked one of Landy’s clinical research assistants for a copy of the study and e-mailed it to Byrne. Should he tell Landy about his conversation with Byrne? He decided to wait, concerned that Genzyme’s scientists and doctors viewed Byrne unfavorably because he had been allied with Novazyme. But, more important, John knew Landy’s team would go over the study submission—as was their job—and who knew how long they would take to pull the whole thing together? No, he wouldn’t tell Hal Landy or anyone else, not until everything was settled. There was only one person he trusted to get this done quickly: himself.
A week later, in late September, John and a half-dozen other senior Genzyme managers and scientists flew to the Netherlands to explain their decision to drop the Pharming enzyme. Dutch newspapers had been filled with stories quoting panic-stricken patients and their families saying Genzyme was ceasing production of the very enzyme needed for their survival. “Do I have to be embarrassed of my son in my old age?” Henri’s mother, who still lived in the Netherlands, had phoned him to complain.1
On the morning after they arrived, the Genzyme group—including John, Landy, van Heek, and McKinney—drove to Rotterdam and met with Dr. Arnold Reuser, the scientist who had developed the Pharming enzyme, and officials from Sophia Children’s Hospital.2
In the afternoon, John and the team met with about forty patients and family members in a conference room at t
he medical faculty building at Erasmus University.The group was large. The incidence of Pompe appears to be higher in the Netherlands, although researchers say they can’t be certain this is true. Before the presentations began, John went around the room introducing himself. He shook hands with a big man in a wheelchair who breathed with a ventilator. John also met the man’s wife. Another woman introduced herself as the mother of a little boy who had done so well on the Pharming enzyme that he was now able to walk. A woman showed John pictures of her daughter who was being treated with the enzyme. A father of another child gave John a brief nod and looked away.
When everyone was seated, van Heek rose first to address the group, speaking in Dutch, promising that Genzyme remained committed to treating the patients—just with a different enzyme. He explained that Genzyme couldn’t afford to take the four enzymes it owned into development and had done a wide-ranging study, the Mother of All Experiments, to determine which one worked best. Landy spoke next, showing a handful of slides summarizing the Mother of All Experiments.
John followed with the development plan. “We plan to conduct two clinical trials, one on sixteen infants, one on sixteen children aged three and younger,” he said. “These are very difficult, time-consuming, expensive enzymes to make, but we’re using the best technology in the world to do it.” He tried to project confidence and authority into his voice, so that the assembled patients could hear that, even if they had to listen to a translator for the exact words. “Ultimately, this will be a more reliable and safer way to make enzyme.”
