But her father’s well-meaning cardiologist was primarily focused on common cardiovascular conditions that typically affect older populations. “My doctor was skeptical about ATTR-CM being an issue for me,” Harvey says. “And there was no treatment, so very few people were being tested. Why test for a disease with no treatment?”
In March of 2018, the Friday before the data of the study was to be officially released, Brenda received a phone call from her team’s statistician. The trial had been a huge success: participants treated with the experimental therapy were seeing better function and quality of life scores as compared to untreated participants as early as six months into receiving the treatment, with a reduction in the risk of mortality of 30%.
“I burst into tears,” Brenda says of hearing the results. “It's a very unique moment for somebody who’s spent 20 years devoted to bringing new medicines forward. It doesn't happen all that often.”
“When we started this trial, it was thought that there were only about 1000 patients worldwide diagnosed with this disease, and we were looking to enroll nearly half of them” to ensure a clear picture of how well the drug may work, Sultan recalls. “These were patients who were very sick. They were thinking about their life and deciding if they were willing to spend time participating in a trial.”
In December of 2013, Pfizer began a 30-month clinical trial to monitor the effects of this experimental therapy and was ultimately able to enroll 441 patients. Brenda says that this particular trial, where success could lead to a medicine that truly extended lives, illustrates an easily overlooked but crucial aspect of drug development: the human element. “With this trial, we knew we couldn't investigate incremental symptom improvements,” she says. “We couldn't think small. We had to design something that would look at life-changing outcomes for these patients.”
As Brenda and her colleagues investigated existing medicines that might help inform their search for a treatment, they evaluated a compound that had already been approved outside of the U.S. to treat a different form of the disease, called transthyretin amyloid polyneuropathy.
In 2012, Brenda and her team began work on a clinical trial to study this treatment in patients with ATTR-CM. But getting there was no easy task. For one thing, the team had little existing data to work with. “There was really limited natural history we could use, and the clinical endpoints needed to establish efficacy were unknown because our study was the first,” says Marla Sultan, vice president and clinical development lead for the rare disease department. And because research into ATTR-CM was so limited, Pfizer’s development team had to leverage a variety of novel technologies and recruitment methods to build the trial from the ground up.
One of the diseases they began to examine was ATTR-CM, a rare heart condition characterized by the misfolding of transthyretin, a common protein that serves as a transporter in the blood. The misfolding leads to the formation of amyloid, which deposits in the heart, eventually leading to heart failure. At the time, ATTR-CM was not only significantly underdiagnosed, but there were also no approved medicines to treat the disease.
At the time, ATTR-CM was significantly underdiagnosed, with no approved medicines to treat the disease.
At Pfizer, Brenda and her team led a strategy focused specifically on rare diseases — a field that has become a key focus area for Pfizer. “It was clear that, although Pfizer had a core portfolio of products focused on rare diseases, it was still an underserved area,” she says. “We knew putting more emphasis on this area of medicine development would be important for us, but also for patients and families with no treatment options available to them.”
In May of 2019, Brenda Cooperstone, chief development officer for rare disease at Pfizer, received a troubling phone call from her mother.
She shared that Brenda’s father, then in his early 80s, hadn’t been doing anything out of the ordinary when he felt a painful twinge in his arm.
“Maybe it was all the golf,” Harvey Cooperstone remembers speculating about his injury. “But it was the first time I believed something was wrong.”
Brenda, a physician by training, suspected her father had ruptured his bicep, and that the rupture had been caused by a buildup of amyloid, an abnormal protein that had deposited on his tendon. This was just the latest in a series of symptoms that had Brenda worried her father might be suffering early stages of a rare disease called transthyretin amyloid cardiomyopathy (ATTR-CM).
Brenda had intimate knowledge of ATTR-CM because — in a strange twist of fate— she and her team at Pfizer had been studying the disease for over a decade, work that ultimately led to development of the world’s first treatment for this fatal disease.
Brenda’s interest in medicine development began in 1999, when she transitioned from working as a nephrologist into a medical role at Pfizer.
“Until then, I knew the pharma industry as the representatives who came to my office to share the latest on their medicines,” she says. “But then I learned about the work being done in research and development and realized that, instead of helping people one at a time, I could have the opportunity to positively impact thousands of patients.”
THE GREATEST GIFT - Video
After 20 years in medicine development, Brenda Cooperstone and her team deliver a breakthrough drug that could change her father’s life.
A story of fate and time:
One daughter’s search for a medical breakthrough
Last year, 60 thousand people participated in our trials around the world.
We are grateful to each person who has taken part.
You’re changing lives for the better.
Breakthroughs that change patients’ lives™
“I burst into tears,” Brenda says of hearing the results.
Pfizer quickly mobilized to prepare submissions for approval around the world and launched a compassionate use program that allowed patients to access the drug prior to formal approval. “The data were clear: the earlier you treat, the better off patients are,” Brenda says. “We pushed to bring this to people as quickly as possible.”
The FDA officially approved the drug in May 2019. But what should have been a celebratory moment for Brenda was clouded by her increasing certainty that her father was suffering from ATTR-CM, and his continued reluctance to be tested. When she learned about her father’s bicep tendon rupture, it was the last straw.
“I yelled. I screamed. I threatened,” Brenda recalls of that conversation. “I told him, ‘If you don’t get tested and you do have this disease, the consequences are terrible. But if we do this now, we have the best chance to make a difference.’”
Finding a suitable patient population was another challenge.
“My daughter’s work to create this drug has been the greatest gift I've ever received,” Harvey says.
Her persistence paid off, and finally her father agreed to be tested. The results came back positive for ATTR-CM. Just six days later, he received his first dose of medicine — as one of the drug’s first commercial patients. “My daughter’s work to create this drug has been the greatest gift I've ever received,” Harvey says. “She has given me a chance to prolong my life.”
Brenda sees this trial as an excellent example of what’s required for companies like Pfizer to bring new medicines to people in need. “I think it can be difficult for the public to understand the years of work required to develop drugs,” she says. “Thousands of people like me, scientists and physicians, invest years of their lives working to bring medicines to the patients who desperately need them.”
And although not every patient who needs these medicines are relatives, in a way, they often feel as though they are. “It's such a strange confluence of circumstances,” Brenda says of her father’s disease and her work searching for treatment. “But my family is no different than any other where somebody is suffering from a rare disease. We have families, kids, and parents. We see the patients that we're trying to help in our own families — and our families in them.”
To learn more about Pfizer clinical trials, visit pfizer.com/clinicaltrials
Her persistence paid off, and finally her father agreed to be tested. The results came back positive for ATTR-CM. Just six days later, he received his first dose of medicine as one of the drug’s first commercial patients. “My daughter’s work to create this drug has been the greatest gift I've ever received,” Harvey says. “She has helped prolong my life.”
Brenda sees this trial as an excellent example of what’s required for companies like Pfizer to bring new medicines to people in need. “For people who don’t work in this field, I think it can be difficult for the public to understand the years of work required to develop drugs,” she says. “Thousands of people like me, scientists and physicians, invest years of their lives working to bring medicines to the patients who desperately need them.”
As the study progressed, Brenda and her team found that many patients who were entering the study with heart disease also had issues like carpal tunnel syndrome and spinal stenosis — the same symptoms being exhibited by her father. “The further we got into the study, the more red flags I saw in his symptoms,” Brenda says. “I told my father, ‘I really want you to be screened for ATTR-CM.’”