Driven by a Common Goal
Bringing potentially life-changing medicines to the people who need them can’t be done alone. It takes a community. It requires collaboration rooted in trust.
At Genentech and Roche, partnerships are a core part of who we are. Nearly half of our medicines are the result of collaborations with other companies and scientists from around the world. Finding partners who share our passion for following the science and are committed to finding new solutions for people with unmet medical needs is a major focus of our daily work.
A Legacy in Hemophilia
“We have a long history of developing new therapies for people with blood cancers, but very few people know that we also played a key role in developing a transformational therapy for people with hemophilia,” says Nancy Valente, Genentech/Roche’s Vice President of Global Product Development in Hematology and Oncology.
In fact, over 30 years ago Genentech raced to help people with hemophilia A, a blood disorder caused by a breakdown in the blood clotting process, where one crucial link—called factor VIII—is missing. Without sufficient factor VIII, people with the disorder can bleed more or longer after an injury, or spontaneously, most commonly in their joints.
Genentech scientists were the first to clone the factor VIII gene, and by licensing this groundbreaking technology to a company called Cutter Biological, we helped create a new recombinant therapy to replace missing factor VIII in people with hemophilia A.
Cloning Factor VIII: A Turning Point for People and Science
For people with hemophilia, replacing missing clotting proteins is a crucial treatment to stop or prevent bleeding. Early treatment options derived from human blood plasma provided people with hemophilia A with their missing protein – Factor VIII – and were seemingly an effective strategy.
When the AIDS crisis hit in the 1980s, it was discovered that many of these products were contaminated with HIV and the viruses for hepatitis B and C, exposing people with hemophilia to devastating diseases each time they received treatment.
It therefore became a moral as well as scientific imperative to clone factor VIII, so a treatment that didn’t rely on donated plasma could be developed. Genentech researchers from diverse disciplines came together to overcome one of the most important scientific challenges of their time.
Cloning Factor VIII: A Turning Point for People and Science
Researchers describe the moral urgency and scientific breakthrough behind cloning Factor VIII.
“That approach made a significant contribution to the community at time when patients were at great risk of acquiring an infection from blood plasma-derived products, but people with hemophilia still face major unmet medical needs,” says Valente. “We knew we still needed to do more.”
Fortunately, a strategic partnership between Genentech, Roche and a Japanese biotechnology company called Chugai Pharmaceutical may help us make another major impact on this community.
"The idea that you could make an antibody do something completely different to what it usually does was an innovative flash."
As with the Genentech scientists, Chugai’s researchers were similarly motivated to find a new approach to hemophilia when they realized, up close, the serious impact the disorder has on people’s lives.
Tomoyuki Igawa, a scientist at Chugai who was leading the antibody engineering team at the time, vividly recalls visiting a meeting of the World Federation of Hemophilia, where he listened to people with hemophilia tell their stories. “You don’t get to hear the patient’s voices very often while you’re researching,” he said.
The stories Igawa heard affected him deeply. “That is when I fully grasped how much pain people living with hemophilia were going through,” he said. “It was frightening to realize that if you don’t have injections multiple times a week, some people could hemorrhage because of this disorder.”
At the time of the visit, Igawa’s child had just been born, and he realized how difficult it must be for parents of children living with hemophilia to administer their medicine. “I looked at my child and saw those tiny veins, and a great sense of sympathy came over me,” he said. In the lab, he was working on trying to find an alternative to the injections of factor VIII that are typically required for people with hemophilia A. “That gave me the motivation as a researcher to keep going,” he said.
A Flash of Innovation
That motivation led Chugai scientists to think outside the box.
They were already working on using therapeutic antibodies against immune-deficiency diseases, and they were closely following the latest advances in antibody engineering and how they were revolutionizing treatments for cancer, brain diseases and arthritis. Antibodies are designed to work by binding to specific proteins that can affect the growth or function of specific cells in the body.
But the idea of using antibodies to help a disorder rooted in problems in the blood clotting process had never been realized before. The team at Chugai hypothesized that if they could find an antibody with the right size and properties, they might just be able to engineer one to slip into the blood clotting chain and bind to the same proteins as factor VIII, potentially doing its job for it.
“The idea that you could make an antibody do something completely different to what it usually does was an innovative flash,” said Atsushi Muto, who was also on the research team at Chugai. “But trying to turn that flash into reality was not easy, and took significant effort and perseverance.”
“We had to screen 40,000 different antibodies over many years to find the one that had the activity we were searching for,” he continued. “It was a bit like a treasure hunt.”
A Common Goal
Genentech and Roche have been working with Chugai since 2002, and a shared passion for groundbreaking science grew over time. The companies were already collaborating on a number of innovative treatment options when this new idea sprang to life in 2012.
"We knew we still needed to do more."
“There was a lot of excitement when Chugai was presenting this molecule to us,” said Robin Breckenridge, Vice President and Chugai Alliance Director at Roche. “They clearly shared our commitment to advancing science and finding creative therapies to fulfill unmet needs.”
“At Genentech, we know that transforming potentially game-changing ideas into reality can be daunting,” says Kate Skrable, Associate Director of Alliance Management at Genentech. “Working with a partner like Chugai that understands the value of what Genentech and Roche can provide to their cutting-edge science is crucial.”
The idea that an antibody could affect the blood clotting process in people with hemophilia A was indeed cutting-edge. But great science doesn’t live in a vacuum. Only by working together, and listening to and collaborating with the hemophilia community, can Genentech, Roche and Chugai reach our common goal to help improve the lives of people living with this serious bleeding disorder. We’re excited to see where this journey leads us.