by Babs Carryer
He decided to keep quiet about this for a while. Above all, he didn’t want anyone else finding out about it. Until he had a plan.
Note to self: Remind students to keep this confidential. Keep lab book home for now. Just for safe keeping.
Chapter 19
May 8, that same year
Dearest sister Pliya,
I am very worried. I think that I have done something wrong in the lab. Dr. Errol has told me this. We have experiment going very wrong. I cannot tell exactly, but I am making mistake and the mice are dying. They are not living. It is my fault. I am not synthesizing correctly the chemicals. If I am not smart enough to do experiments correctly then I will not be able to stay in the United States. Dr. Errol has told me that if I cannot fix the mistake he will not keep me in the lab. Then I will have to come home. And I would love to see you so much, my dear Pliya, but my heart will be broken from being sent home. I want to stay in the United States, so I work all night for three nights to fix my mistakes. I do not want the mice to die. This is sad and wrong. I am hoping that I do not write to you next with the date of my arriving at home. I am hoping and praying that I will fix my mistakes. And the mice will not die.
Please pray for me my darling sister as I pray for you every day of my life.
Your sister who is mistake making,
Shala
Chapter 20
Christmas, three years before the incident
“OK, I’m nearly packed!” I yell at Neal from the bedroom of my apartment. I go to the closet to get out my suitcase. “Two minutes.”
“Great,” Neal says. “I’ll just help myself to a glass of scotch, OK?” I know he’s ogling The Balvenie Scotch, which he had given me as a present. I had kept it for special occasions. Well, I tried. It was half gone I saw as Neal poured.
I take all of the articles I have accumulated about how to get a non-FDA approved drug to patients and stuff them into the bottom of my suitcase. I grab a few clothes. Oh my, we’re going skiing. Think, Brie. It will be cold. I open my chest of drawers and throw in a few sweaters. Where’s my silk long underwear? Do I have ski pants? These old gloves will have to do. Shoot, these goggles are missing a strap. I throw them all into the suitcase.
“Brie, honey. We have to go!”
“I know, I’m nearly ready.” Gosh, where is that pretty nightie? I’d better have one. I throw a few other things into the suitcase and slam it shut. “I have to bring my computer, OK? I have to work some while we’re there.” I think about the research I am doing, hoping to find a way to get my dad our HD66 drug, pre-FDA approval and not part of a clinical trial. I found out too late for our Phase II clinical trials and too early for Phase III.
“I figured you would need to work some,” Neal says as he walks into the bedroom and lugs my suitcase off of my bed. “Come on, honey. We have a plane to catch!”
We are heading to Vail. We ended up with Colorado because I didn’t want to take the time off go to Europe, and it’s a bit early for Canadian snow. It could be early for Vail too, but it’s a charming village, even if the snow is not great. Plus, it’s a direct flight. And we can spend a couple of days in Denver. I have cousins there, and I love the mile-high city. “The Denver Art Museum is top notch, Neal. I can’t wait to show it to you.” It will be easy to connect to the Internet at their house. In case I need to do more research.
“Can’t wait to see it, Brie. With you.” He gives me a long kiss.
“Hey, we have a whole week for that,” I say, spying another article I had printed out. As he releases me, I grab it and stuff it into my purse.
“Yep, can’t wait for that. Looking forward to it!” He looks at me with a lascivious grin. Today is actually Christmas. We elected to leave on the holiday itself to save money and to avoid the issue of where we would spend it – which family. Our plan was to stay at Vail through New Year’s Day. Neal is splurging on a ski-in-ski-out condo. “This will be so special,” Neal reminds me.
I am both dreading and looking forward to the trip. I have done nothing about getting myself tested for the huntingtin gene. I can’t get any perspective. Finding out is permanent; once you know you carry a dreaded disease, there is no turning back. It will flavor the rest of my life. I am not up to that. Not yet. I reason with myself that I have actually decided – I WILL get tested. The question is when? In my darkest moments in the middle of the night I am consumed by the fear of being rejected because I carry a mutant gene. I don’t think that Neal would drop me because I am defective. But it’s scary just the same. I’m not ready to test it, to test him, to test us. I want it all to go away for a few days. I want to have fun in Vail, to postpone the inevitable. But I suspect what he wants to ask me… I shiver with excitement and dread.
“Come on, Brie, time to go!”
…….
Four days later, December 29
Little did I imagine what “postpone” meant. “It’s never icy at Vail, not compared to East Coast skiing,” I had assured Neal, as I took off down the slope on our first run. “Brie, wait,” Neal had called after me. But it was too late. I have been on skis since I was five. You do that in New England. I’m no racer. I don’t do moguls, but I can ski passably well, and I love the speed. But the conditions that day… I can excuse myself by saying that Colorado ice at 10,000 feet is not like Vermont ice, but it doesn’t really help.
I broke my tibia they tell me at the hospital. After the X-rays, during the consultation, I hear the word “surgery” before I pass out. When I wake, Neal is there. He tells me that they had to install pins and plates in my leg. Titanium.
“The screws will outlive me,” I grin at Neal. He looks so worried.
The crisis consumes us for three days. We had to rent a wheel chair upon leaving the hospital. I learn that you can’t really access ski-in-and-ski-out unless you can climb stairs, ride the chair lift, and walk from the parking lot to the condo building. Neal talked to the manager of the resort and tried to change rooms, but it was too close to New Year’s Eve and they were solidly booked. He had to carry me across the threshold. “Oh, honey, how romantic,” I said as he staggered through the door, nearly dropping me.
On the couch, with a glass of Merlot in my hands and Percocet in my blood, I tell him to relax, that we can manage, but he is stressed. I have escaped a very difficult conversation, and he is way too busy tending to me to be romantic and propose. I know it’s ridiculous to feel so relieved but I am. He catches me laughing to myself. “What on earth are you finding that is funny?” he demands.
“Don’t worry, honey,” I cover. “I was just imagining all of the jealous folks thinking that we are on the slopes, and little do they know…” And so it goes.
“Thank God the Quixotic office has an elevator,” I chuckle. And then I think of what Errol will do when he sees me. He will be merciless, I think with a smile. I glance over at Neal. He is sound asleep on the recliner. I reach into the bag next to me and pull out the papers that I have been waiting to read.
Chapter 21
February 6, that same year
Snow flurries waft down from the gray skies of Pittsburgh. Winter has been settling in since early January – quietly, silently, but firmly. It seems like it will never end. My leg is healing, but slowly. I still have to use crutches. I sip my Peet’s coffee and stare out of my kitchen window. The weather reminds me of “Beclouded,” the poem we all learned in third grade because she wrote it in Amherst:
“The sky is low, the clouds are mean,
A travelling flake of snow
Across a barn or through a rut
Debates if it will go.”
Emily Dickenson
So far, I have not come up with a strategy about my dad and HD66. I have to wait for the final clinical trial. I’m impatient. It’s taking a long time to get there. Everyone thinks that startups move quickly, that everything happens in a rush. That’s partially true. The sense of urgency in a startup is paramount. What most people don’t know is that a startup
is like anything else – it takes the time it takes. It’s slow. Like making a movie. Or writing your first book.
Matt and Errol have just come back from an international conference on neurological diseases. They presented our data on HD66 – the positive results of the Phase IIA and IIB trials. That morning, at our on-the-same-page meeting, they told us what happened after they presented.
“Oh it was like Canadian geese landing after a long migration flight,” Errol started. “There was a flurry of ‘em, and they kept coming. Squawking and chattering, they all wanted to know who we had talked to, who we were talking to, and would we be interested in…” Errol starts acting like a goose and picks up my crutches waving them around like wings.
“We wowed them, it’s that fucking simple.” Matt stated. “Now we have their attention. Stan, prepare your playbook; we are going in!” Matt has one of my crutches and he thrusts it like a sword.
Stan laughs, “I’ve already started.” He parries with the other crutch. The meeting goes on, and the mood is positive.
The next few months will be taken up with negotiating a deal with a big pharmaceutical company that has the resources to pay for the Phase III trials. The Phase III trial will have hundreds of HD patients who will be enrolled for a period of many months. I want one of them to be my dad.
Assuming HD66 comes through that trial, our theory is that we will be acquired. Everyone would make money, from our investors to us. And patients would finally have hope. I hear Clov from Beckett’s Endgame in my head: “Finished, it's finished, nearly finished, it must be nearly finished.” This is the game that entrepreneurs play – build value and exit. Only it’s not a game for me, my dad, and the thousands of patients with HD.
Matt and Jim are talking to all of the major companies focused on neurodegenerative diseases. They’ll be flying all over the world for these discussions, “Asia, Europe, Japan,” I listed their itinerary to Gigi after I had made the flight arrangements.
“Wow, Brie, you made these awfully close together. Will they mind?” No they won’t mind. They’d do it even faster if they knew how desperate I was.
“There’s no one who doesn’t know about Quixotic. The timing is right. This is tight, Brie, but it’s good.” Matt said when I delivered the travel documents to him. “You’re right to hurry us up.” Little does he know.
“What will happen is a bidding war between several companies,” Jim told me when I explained their itinerary.
“Won’t that take more time?”
“Of course. It will prolong the deal, but it will mean that we get the best one.”
“Is there no way to do a deal quickly?”
“And why would we want to do that?” Gigi asked with a red-lipped smile. “This will be so much more fun!”
“What does Errol think?” I ask.
“Oh, he wants to hurry it up too,” Matt said. He had been standing at the door. “Errol is really no help now. We’re not taking him on these trips. He’s fucking brilliant, but this is business. Plus his schedule makes it hard for him to travel.”
“It’s challenging for him to get away,” Gigi remarked. “But not impossible…”
Hurry up and close a deal! I went back to my stack of papers. Somewhere there has to be an alternative. I don’t want to wait.
…….
The following week, February 15
“Darn!” I throw down the article I was reading in disgust. Another plan down the drain. I couldn’t slip my father the drug on the side. First of all, I didn’t really have access to it. While I knew some basic things about the science of HD66, I didn’t know my way around the lab. I didn’t know the exact formula and, while I figured much of that was in the patent language, there was additional know-how that Errol had in his head. His lab technicians might know part of this, but it was unlikely that they would know all. That’s why they call it a trade secret.
Secondly, giving my father the drug would be unethical. From my research I learned that it would jeopardize Errol’s medical license. Without an Investigational New Drug Application to the FDA and Institutional Review Board oversight, neither of which we could get for a single patient, it would be unethical. Given his MD status, if a random patient were to receive the drug, and the authorities found out about it, he would be penalized. At least that’s what I surmised from some cases in different diseases. The doctor associated with the case I had just read about had been prosecuted and prohibited from practicing medicine for the rest of his life. I couldn’t risk that. Errol would kill me.
Even if I ignored those risks, and Errol agreed, it could blow our chances of FDA approval. “The notoriously fickle FDA,” Errol told me, “holds the key to our future.”
I know that, if we don’t get FDA approval, our company would be toast. If I did this on the side I might wreck the path to value creation and exit. I could be sued by the shareholders. They would all kill me.
…….
The next day, February 16
“Oh my gosh!” The implication struck me like a lightning bolt. I jerk my leg in surprise and wince in pain as it bangs my desk as I read the tagline below the YouTube video I found as a result of my research.
“Compassionate use is a designation by the FDA whereby a patient can receive a drug that is not yet approved.”
I pick up another article I had printed from my Google search and read:
“The designation of compassionate use means a company with a new drug can treat a patient with a serious or immediately life-threatening disease who has no comparable or satisfactory alternative treatment options. Compassionate use is reserved for diseases for which there is no cure.”
“HD fits the criteria of no cure,” Jim tells me when I question him a few minutes later. “Why do you ask?” Jim looks at me quizzically, his fuzzy eyebrows furrowed.
I am careful how I phrase my reply, “Oh, you know, just thinking about patients.”
Jim gives me a kind smile. Sometimes I think that Jim can see into my soul. I am not ready to tell him, not yet. Besides, Jim has not been around a lot lately. He has lost weight and looks pale. I don’t want to bother him with my problems. “You’re thinking of Errol’s patients?”
“Of course. This would be good for them. And others.”
“Hmmm, let me see what the others say,” Jim ponders.
“We could give it to all of my patients!” As a seasoned investigator, Errol knew the tenets of compassionate use trials, but he had not considered it for HD66.
“Yes of course,” Gigi admits. “But from a theoretical point of view. I hadn’t actually considered it. For us, I mean. I don’t have any direct experience, never knew anyone who’s done this. Jim, did you know?”
“I’ve heard of this, read about it generally. It’s not new. But no, I never realized that we could do this. Brie brought it up. Matt, what do you think?”
“What? Compassionate use? Fuck that. We can’t do that. We have a company to run. That’s a dead end street.”
“What do you mean?” I ask.
“Stan will tell you best,” Matt responds. “Hey, tall boy,” he grabs Stan who had wandered by, probably having heard all of us talking. “What the hell do you know about compassionate use and why the fuck aren’t we doing this for Huntington’s sufferers?”
“Well, I can tell you the legal issues for a start. It’s a challenging designation to actually implement. The first problem is liability. Since there is no guarantee of being cured, the patient has to be informed that there is risk that the drug doesn’t work, that it might have side effects, that it might not be safe. That creates legal paperwork as you can imagine.” Stan pauses and stares at the ceiling for a moment. “The only way to know that a drug is effective, that it works, is through a controlled study. Giving early access to patients outside of this is very risky.”
I don’t care about the risks of the drug not working. I know I could convince my father and mother to not care as well.
Stan’s gaze returned to ho
rizontal. “Secondly, the risk of early access is that we could have a safety issues in an uncontrolled setting that could hurt our chances of approval. You could wreck your chances of advancing the drug, which defeats the purpose of what we are doing.”
He looks out the window. Returning his gaze to us, he continues, “A third issue is picking who gets the drug. What’s the criteria? How do you say ‘yes’ to one patient and ‘no’ to another?”
“What if we could address some of those issues?” I ask. I know I sound too earnest. “I mean, we all believe that HD66 works. That it cures people. Can’t we find some way? To not let a few legal issues get in our way of our mission?”
“Oh Brie, that’s beautiful and noble and that’s why we love you, but understand that there is an inherent contradiction in the compassionate use designation,” Gigi states. She is treating me like a child. With pursed lips, she continues, “Stan can best explain about how the designation favors big companies.”
“She’s right. The designation favors large companies with deep pockets. The exception to FDA approval for humanitarian use has financial implications for the company that produces the drug. Companies can either donate the investigational drug to severely ill patients, or they can charge for the direct costs associated with manufacturing the drug.” Stan stares at me closely. “There’s no reimbursement, no real payment.”
“There’s no business model in doing this.” Gigi says firmly. “As painful as it is, a company like Quixotic cannot afford to embrace compassionate use. We’d go broke.”
“The main issue is that, legal issues aside, once you have that designation, you have to comply. You can’t give the drug to one qualified patient and not to another. Do you say yes to everyone?”