by Geeta Anand
An arm shot up in the audience. “How do we know the rat enzyme will work as well for my son?” the woman who had raised her hand asked angrily. In the morning meeting and now, the Dutch had been derisively calling the internally developed Genzyme treatment the “rat enzyme” because it was grown in CHO cells, taken from Chinese hamsters.
“As Hal just described, all our animal studies indicate it will not only work as well, but better,” John said. “Let me also say our enzyme is not a rat enzyme. It is an enzyme made in a very sophisticated process using tissue from hamsters to produce human enzyme. The hamster cells are a production facility.”
“Who is going to take responsibility if our children do not do well on the rat enzyme?” another parent challenged.
“This is not a decision we made lightly, believe me,” John said, trying to convey his deep sympathy. “We made it based on scientific evidence. As Jan has said, new patients will not be put on our enzyme until we are sure we have enough in storage to supply your needs. We are making sure we have enough enzyme to supply each and every one of your needs—even though it means many other Pompe patients in the world will have to wait longer, and perhaps die, waiting to be treated.”
“And Mr. Crowley, why don’t you tell us when your children began receiving this enzyme?” the same parent asked accusingly. With a shock, John realized that everyone in the room knew about his own situation and assumed Megan and Patrick were being treated.
“When we’re talking about supply issues, I know what we’re talking about because I live it,” John said. “I know about how drug supply affects everything you can do in drug development. My children are so weak they can’t sit up or even hold their heads up for long anymore.” His voice was shaking, and he paused to try to steady it. “They—they are in wheelchairs and on ventilators. They get weaker every day. And my children still have not received one single drop of enzyme.”
When John sat down, still struggling to compose himself, there was absolute silence in the room. Nobody—not the parents, not the patients, not even the Dutch doctors and scientists—asked another question. After van Heek had thanked everyone for attending and the meeting had ended, the wife of the man in the wheelchair hugged John. “I hope your children get treated soon, Mr. Crowley,” she said.
Finally, only John and McKinney remained in the room. “It just killed me to hear these people complaining about being put on a different treatment,” John said bitterly. “If Megan and Patrick had gotten enzyme like they did three years ago, they might be running around like regular kids now. I’ve failed my children, Tony. I have failed my family. I don’t know what I’m doing here anymore.”
John arrived home after dinner on a Friday night soon after to find a message from Dr. Byrne. He stepped into his study and dialed him back.
“This rarely happens, but our application went up and down in one day. We got the green light from our review board,” Byrne said. “We’re set to go. We could probably get this together in two weeks.”
For once in his life, John was amazed at the speed with which something had happened.
“Can I come down tomorrow?” he asked, sounding a little dazed. “Yes, yes, I know it’s a Saturday but I’d like to come and talk face to face.”
John arose at 3 A.M. the next day to catch the first flight from Newark to Jacksonville. On the plane, he read the new protocol Dr. Byrne had gotten approved by his review board and e-mailed back the night before. John saw that Byrne had avoided the conflict of interest by writing a study for six children so that Megan and Patrick were not the only patients. Byrne had combined elements of both his original Novazyme application and Genzyme’s Sibling Study. John knew now that Landy would have real trouble with this protocol, but again, he decided that he would think about that later. For now, he would go to Florida and get everything set up. If he had enough momentum, Landy and others at Genzyme would piss and moan but would eventually get out of the way.
John drove the two hours from Jacksonville to Gainesville, forcing himself not to speed, despite his excitement. He remembered Aileen’s embrace when he told her the night before, and Sharon’s scream and Megan’s eagerness to get to Disney World. It was seventy degrees and sunny as he drove on the wide, palm tree–lined roads toward the brick buildings that made up the University of Florida campus and hospital. John parked in a garage and made his way across the street and up in an elevator to a conference room where Byrne and Dr. Carolyn Spencer, also a pediatric cardiologist, awaited him.3
The two doctors were warm and enthusiastic as they explained the trial protocol they had designed together. They walked him through sliding glass doors and into the bright new clinical trial research center where they said Megan and Patrick would receive their infusions of the experimental medicine. Children had painted bears, dolphins, and their names—Michael, Jessica, Melanie—on the ceiling tiles. What a wonderful place for his children to finally be treated.
That afternoon, Byrne’s head nurse, Julie Berthy, drove John around Gainesville for several hours to look at apartments. He found one—a three-bedroom unit on one level for $1,100 a month—that he decided would work just fine.4
Back at his hotel, John bought five blue and orange Gators T-shirts for the family. If they were going to live in Gainesville for a while, they would have to become University of Florida football fans. No team could ever supplant Notre Dame as the Crowley family’s favorite football team, but the Gators were becoming a close second, at least for John.
That night, John chatted with Drs. Byrne and Spencer at the sunken sports bar at the Hilton Hotel where he was staying, a football game playing on the thirty-five-inch television.
“How soon can we begin, Barry?” John asked.
“We need to schedule a surgeon, an anesthesiologist to implant the ports,” Byrne said, referring to the tubes that allow regular infusions without sticking patients each time and stressing their already fragile veins.
“Getting the contracts signed by company and the university usually takes some time,” Spencer added.
“I’m in charge of the program, and I’ll make sure it gets done quickly,” John said firmly. Then, with a little less certainty, he asked, “Can we stick a needle in their arms and infuse them first and do the surgery later?”
“We could. But why would you?” Byrne asked slowly, putting his drink down on the table.
“Once the children are infused with enzyme, the trial has officially started and nobody is going to stop it. Until then, I’m worried someone at Genzyme or somewhere else is going to think of some reason again for a delay.”
“I don’t know if I can get everything lined up to begin the trial next week,” Byrne said, after a pause. “But I’ll give it a shot.”
On Monday afternoon, John was in his Princeton office, talking on the phone, making arrangements to rent medical equipment and a handicapped van in Gainesville, when Landy called.
“How are you, Hal?” John said, trying to sound casual as he covered his eyes with his free hand. God, he hoped the news of the Florida trial hadn’t yet traveled to Cambridge.5
“Not well, John,” Landy said. His voice seethed with barely contained rage. “We just got a call from Barry Byrne’s office about shipping drug to Florida. What is the meaning of this? What the hell do you mean by doing this?” It was Landy’s job, not John’s, to write and submit applications for clinical trials.
“Hal, you knew we were looking for Plan Bs,” John said weakly.
“I didn’t know you’d gotten hospital approval,” Landy snapped. “I haven’t even seen the protocol. John—what the fuck are you doing?”
“Calm down, Hal,” John said. “I’ll come up there and we’ll work this out.”
“ ‘Calm down’?!” Landy erupted. “You have no idea. People here are very upset. You have no idea of the trouble this is causing. This place is in an uproar!”
“I’m sorry, Hal,” John said quietly. “Of course we want your approval and guidance. I’m s
ure we can work this out. I’ll come up in the morning and we’ll figure this out.”
“ ‘Work this out’?” Landy repeated incredulously, shouting again. “You have no idea—you have no idea what you’ve done. John, you may have jeopardized your chances of ever getting your kids treated.”
26
“You Can Tell Megan”
Fall 2002
Cambridge, Massachusetts; Princeton, New Jersey
The next morning, Dr. Landy sat in his office shaking his head as he read the protocol that had been approved for the clinical trial in Florida. His anger had subsided, and he was beginning to blame himself for what had happened. He should have gotten John’s kids treated sooner. It was actually remarkable, he thought, that John had maintained his objectivity for so long. How could he have missed the fact that John was going over the edge?1
But the more he read of the Florida protocol, the more certain he became that he could not go along with it. It was markedly different in several areas from the Sibling Study he had put together—most notably in the number of patients that would be enrolled. Byrne’s protocol said they would enroll up to six patients, when the Sibling Study was set up for just two.
While he scrolled through the document, John appeared at his door, looking downcast and apologetic. “John, this protocol is completely different,” Landy burst out, pointing to his computer screen. He scrolled down the document to highlight each section that varied. “You can’t just submit things. We have standard protocols. We have quality control checks. This is not the Sibling Study.”
“But this will solve the conflict-of-interest question,” John said.
“But we don’t have drug for six kids,” Landy said heatedly.
“We do have extra drug—one of the children in the Duke trial died. We don’t have to enroll all six children at once. We could start with three and add more if the drug supply improves. There’s every indication it will. The bioreactors are producing drug well.”
Landy shook his head. He pointed to other differences. “The preclinical section describes results of animal experiments using the Novazyme enzyme instead of Genzyme’s,” he noted, angry again.
“We can fix everything. I’ll make all the changes you want. I’ll make it two patients, I’ll take out the Novazyme animal stuff, I’ll change the cardiac end point,” John said, pleading. “It’ll take me an hour on the word processor.”
“You can’t do it. We have strict protocols,” Landy said, adamant.
“Okay—let your team do it. Barry says he can send a notice of amendment to his review board this week,” John said.
“We don’t have the resources to do it so quickly,” Landy said. “We’re stretched to the limit with 1602 and 1702,” the two main clinical trials whose protocols the company planned to submit to the FDA the next month.
John stopped, realizing suddenly that Landy had meant what he’d said the previous night. He didn’t intend to allow the Florida trial to go forward. And he, John, didn’t have the power to force Landy’s hand—at least not without some help.
John walked up the stairs to van Heek’s office, hoping to convince him to overrule Landy. Van Heek listened as John described what had happened, not asking a single question. When John had finished, van Heek said soothingly but unconvincingly, “I’m sure, John, that we can work this out.” Then he stood up, signaling he had another meeting. As John walked out of the office, he knew van Heek was not going to come to his rescue this time.
What John didn’t know was that Henri and the rest of Genzyme’s senior management had already heard about the Florida mess. Henri had personally phoned Landy to reassure him that he—and not John—had authority over all clinical trials involving Pompe disease, including the Sibling Study. “John can’t be trusted on this one—you are going to have to hold the line,” Henri said. “We agree with you that John has gone too far this time.”2
The next evening, the phone rang in Genzyme’s satellite office, the same colonial on Nassau Street in Princeton that John had rented for Novazyme. It was Genzyme’s soft-spoken general counsel, Tom DesRosier, delivering “an off-the-record heads-up” that two other lawyers would be calling in a few minutes to ask him some questions. Before long, the attorneys were on the line telling John they were following up on complaints he’d violated company rules by submitting the protocol to the University of Florida without getting the required sign-offs.
“Guys, off the record—I think this is bullshit,” John fumed. But for the next fifteen minutes he patiently answered their questions.3
John sat at his desk for the next hour, uncertain what to do. As a lawyer himself, he knew the questions about violating internal rules would go nowhere. But he realized not only had he lost the Florida battle, but his credibility as a leader of the Pompe program had also taken a big hit. Unless he pulled back, he would lose his job—and his influence, however small, over the clinical trials of the Pompe drug. He sat down at his computer and began typing, pausing with every few words.
“I know there has been a lot of discussion regarding the treatment of my children. I’m sorry for any confusion it has caused,” he wrote. “As we all know, the most important thing is that the entire program continue to move forward. There is a perception that my children’s trial is interfering with the larger program. I will let the doctors in Florida know we are withdrawing the request for treating my children. We can revisit the Sibling Trial after the 1602 and 1702 studies have been submitted to the FDA,” he finished.4
By the time John had finished, the rest of the staff had left for the day and the office was quiet. He read over his e-mail again, staring at the screen, not wanting to give up on the Florida trial that had seemed so close only two days ago. Finally, he looked at the clock and saw it was 6:30 P.M. As usual, he was late heading home. He hit the “send” button and left the office. More than anything that had happened on this horrible day, he dreaded the task that lay ahead.
John arrived at home and went right to his study. Aileen, who usually let him stay there, stepped inside and stood by his desk until he looked up from his computer.
“How was your day?” she asked tentatively, having picked up on his vibes enough to know something was wrong—again—with the trial plans.
“Long day,” he said noncommittally, looking back at the computer screen.
“What’s the deal with Florida? Sharon and I have been packing all day. We need to know when we’re leaving.”
“We’ll get the kids treated, but not now. Just give me more time,” he said, still avoiding her eyes.
“How much time?” she asked.
“I don’t know,” he said, wearily. “At least another month until I can get another study up and running.”
He sighed and looked up. Aileen’s green eyes glazed and then hardened. “Okay, John, two things,” she said, her voice thin and without emotion. “Next time, just tell me when we’re ready to get in the car and drive to the hospital.” She turned to walk briskly from the room.
At the door, she paused. “And one more thing—you can tell Megan.” Without looking at him, she walked out the door and disappeared.
John followed her to the playroom, where Megan sat at the computer playing a Barbie Princess game. He pulled up a chair beside her and reminded himself not to get too emotional.
“Honey, you know we’re really, really close to getting you Special Medicine,” he said.
Megan backed up her chair quickly and swirled around to face him. “Yes, we’re going to Florida,” she said, nodding.
“Well, Special Medicine is almost ready, I’m just trying to make it perfect,” he said. “I just wanted to tell you that Special Medicine is taking a little longer to get ready so we won’t be going to Florida this week. It’s going to take a little more time.”
Megan lowered her chin on her hand and rested it there, sitting silently for a minute, eyes lowered.
“I’m sorry, honey,” John said.
Without a word, Me
gan turned and resumed her game.
As John walked slowly across the kitchen back to his study, his heart raced and his stomach tightened. He had trouble catching his breath. A wave of nausea swept over him, a mix of anger and anxiety. Someone at Genzyme should have been forced to tell Megan. Why couldn’t Aileen or someone else have helped out by telling her? Why did everything end up on his shoulders?
The phone was ringing in his study. He picked it up, knowing it would be van Heek, who had been trying to reach him all day. “John, I’ve got a bad feeling about all of this,” van Heek said. “I’m so sorry, I wish there was something I could do to help. I wish I could help, but my hands are tied.”5
“It’s all right, Jan,” John said tiredly. Even soothing other people’s consciences came down to him. “I know it’s not your fault.”
* * *
The weekend was a struggle. Aileen had arranged for the family to go to pick pumpkins as they did every year, but even she wasn’t able to get up much enthusiasm. The family returned home Saturday afternoon with ten pumpkins but absent the annual picture of everyone in the pumpkin patch.
John barely slept Saturday night and awoke Sunday to the sound of a car horn. He raced down the stairs in his boxers to find the day nurse blaring her horn trying to get someone to wake up and let her in.
“Couldn’t you knock?” he said to her. She ignored him and started up the stairs. A few minutes later, John overheard her admonishing Aileen for locking the door that was usually left open. John’s temper flared and he marched down the hall shouting, “Get the fuck out. Now. And I promise you, you will never, ever return here.” She’d been with them for almost four years.
Megan, who was in the room with the nurse, began to cry, and John regretted having lost his temper. “Oh Megan, it’s okay,” he said softly, giving her a hug. “Even big people have disagreements.”
