Jane Smith, Head of Rare Blood Disorders Public Affairs and Patient Advocacy, featured in the video below. Pictured here with her son Leland Smith.
Pioneering scientists Ekta Seth Chhabra and Jennifer Dumont offer a glimpse into innovation in hemophilia research and therapeutic development over the past half century.
For people with hemophilia, a group of rare genetic disorders in which the blood fails to clot properly, the disease is never far from mind. Today, many patients must infuse themselves regularly with the blood-clotting protein their bodies lack—factor VIII in the case of hemophilia A, and factor IX in hemophilia B—to prevent frequent, sometimes life-threatening bleeds. And when those factor levels dip below a certain threshold, as frequently happens, patients may be at risk. Knowing this, people with hemophilia need to consider their plans carefully—even for activities like yardwork or basketball practice.
Today’s hemophilia treatments are life changing. But they are neither cures nor magic bullets, leaving people with hemophilia and their families to shoulder the burdens and worry that come with a chronic, debilitating condition. Now, a new wave of innovation is cresting, enabling the development of novel treatments that could help people with hemophilia live the lives they choose. Here, two experts in hemophilia research and medical affairs share some of the seminal moments that changed the field of hemophilia, and talk about how science is driving a crop of new investigational therapies.
Making hemophilia treatments safer and longer lasting
“One of the biggest moments in the history of hemophilia was when freeze-dried, plasma-derived concentrates became available in the 1970s,” said Jenny Dumont, Senior Medical Director. “These enabled home care and self-administration for patients, which was a huge advancement for the field.”
Tragically, in the 1980s, many people with hemophilia were treated with contaminated products and became infected with HIV and/or hepatitis C. Lives were lost, and many suffered long-term health effects. “It was a very dark time in hemophilia treatment, and a turning point for both patient advocacy and science,” said Dumont.
In the 1990s, another critical milestone was reached: the development of recombinant products, which use DNA technology to generate clotting proteins in the laboratory. “Patients were no longer dependent on clotting factors derived from human blood,” said Ekta Seth Chhabra, Distinguished Scientist. “Recombinant products are safer because they carry a much lower risk of transmitting infectious diseases.”
Recombinant clotting factors not only proved safer, but also enabled prophylactic treatment—meaning people with hemophilia could more safely infuse at home to stave off bleeds, instead of treating bleeds after they happened. The result: life expectancy increased by decades, approaching that of the general population.
But nature designed clotting-factor proteins to be relatively short-lived, so people with hemophilia would still need to infuse clotting factors frequently. That situation remained unchanged for the next 20 years. Then, in 2014, a new kind of recombinant clotting factor emerged. Advanced protein engineering gave rise to molecularly enhanced versions of blood clotting factors that persist for much longer periods in the bloodstream. With such longer-acting products, many people required fewer infusions per week, which meant less time focused on treatment.
A Timeline of Innovation in Hemophilia
A selection of important moments in hemophilia research and development over the past half century. Events from 1970s-2010s excerpted from a comprehensive timeline published by the Hemophilia Federation of America (accessed at https://www.hemophiliafed.org/updated-historical-timeline/ on July 2, 2021).
The right medicine at the right time
While longer-acting clotting factors (extended half-life therapies) have proved to be a remarkable advance, not all people with hemophilia benefit from them. Recognizing this, Sanofi scientists are harnessing different technologies to create novel therapies for people with different needs.
“When it comes to hemophilia, there is no one-size-fits-all treatment,” said Seth Chhabra. “Even brothers who share the same mutated gene can require different types of treatments at different times.”
One line of investigation—a collaboration with Sobi—includes the development of a higher-protection, longer-lasting therapy designed to break through the "von Willebrand ceiling" for people with hemophilia A without inhibitors. The investigational therapy is based on a an elegantly engineered fusion protein, made up of different components that are molecularly stitched together into a single unit.
This journey to engineering this fusion protein has been neither quick nor easy: Seth Chhabra and her colleagues tried more than 400 iterations before landing on this one.
“We are heading toward a time when patients will have a wide range of treatment options–together with their physician, they will be able to choose what’s best for them based on their own needs and how they want to live their lives," said Dumont. "The field has really made amazing progress, and that’s really exciting to see for patients and their families."
Another project underway at Sanofi involves small, interfering RNA (siRNA) technology. Scientists are investigating how siRNA could help rebalance the network of proteins in the blood responsible for clotting. In people with hemophilia, the lack of factor VIII or factor IX in this network already tips the balance toward bleeding.
siRNA technology may make it possible to tip the scales in the other direction—toward clotting—by rebalancing one of the anticoagulant proteins, called anti-thrombin. This approach does not replace what's missing; rather, the goal is to help rebalance the blood-clotting network. It is of particular interest in developing therapeutics for people with or without "inhibitors" that cause the body to reject factor-based treatments.
The goal: To live without constant worry
Researchers at Sanofi hope the new therapies under development will help change the paradigm of hemophilia treatment.
“It’s important to realize that hemophilia doesn’t just affect individual patients, it affects entire families,” said Seth Chhabra. “Imagine teaching your kid how to give themselves an intravenous injection. Or trying to remember if you infused your child before you left for work. The ability to not think about this disease, to not worry about it every single day, would really be a game changer.”