Earlier this year the FDA approved two new breakthrough therapies for hemophilia patients — Alprolix and Eloctate.
Two landmark therapies for hemophilia won FDA approval earlier this year, capping off one of Mass General Brigham's top innovator's 22-year journey of a failed laboratory experiment to dazzling success. Earlier this year the FDA approved two new breakthrough therapies for hemophilia patients — Alprolix and Eloctate. Alprolix is a recombinant protein to treat patients with Hemophilia B – characterized by the inability to produce a clotting protein known as Factor IX. Eloctate, also a recombinant protein, will help patients who suffer from Hemophilia A, characterized by the inability to produce Factor VIII, another clotting protein. Currently hemophilia patients face a lifetime of injections of exogenous Factor VIII or Factor IX proteins. Both Alprolix and Eloctate are designed to substantially reduce the number of injections. If not for a careful eye, the original discovery that led to Alprolix and Eloctate might have been written off as a failure, says Mass General Brigham researcher Richard Blumberg, MD, Chief of the Division of Gastroenterology, Hepatology and Endoscopy and Co-Director of the Biomedical Research Institute at Brigham and Women's Hospital, a professor of medicine at Harvard Medical School, and Co-Director of the Harvard Digestive Diseases Center. “A postdoc walked into my office on July 22, 1992, with what he thought was a failed experiment,” Blumberg recalls. “And thank God he did, because if he hadn't, I wouldn't be here discussing this today.” Blumberg's lab was using monoclonal antibodies to detect specific molecules on the human epithelial cell surface. But the experiment wasn't working that day—or so it seemed. The control antibodies, supposedly incapable of binding to proteins on the cell surface, had somehow attached to a molecule of unknown identity. “He was upset about this because it shouldn't have happened. Those should be the negative controls,” Blumberg says. “But I immediately thought that it looked just like a MHC class molecule. If you look at the picture, it's the squeakiest clean class I-related molecule that you've ever seen. You could put that on the other side of a football field and I'd recognize it. I knew from the literature that the only molecule that could have that property, at least as described at the time, was the neonatal Fc receptor.” There was just one thing. “At that time, the neonatal Fc receptor had not been described in humans. These were human cells. And the neonatal Fc receptor had not been described in adult life. These were adult human cells. I knew that this was pretty cool,” Blumberg recalls. “All of this—and I'm being honest here—flashed through my mind in about 30 seconds. And the rest is history.” Thus began a journey marked by collaboration, perseverance, and good luck. The neonatal Fc receptor (FcRn) was already known to extend the half-life of the IgG antibody, but Blumberg and two others—Neil Simister, a Brandeis researcher who originally cloned the neonatal Fc receptor (FcRn), and Harvard epithelial cell biologist Wayne Lencer—realized that the receptor could do far more. They set their sights on using FcRn-based technology to sustain the half-lives of blood clotting factors, large molecules with very short half-lives that are absent in patients with hemophilia and must be injected frequently to prevent or control bleeding. The next year, Syntonix Pharmaceuticals was launched, sparking a decade of research and clinical trials. Syntonix was sold to Biogen Idec in 2007. “This entire program—20 years of NIH funding; the idea for the company; all the jobs that were created; all the ideas that were generated; all the publications in my laboratory, at Syntonix, and subsequently now at Biogen Idec; these products now allow patients to be prophylaxed for the first time—none of this would have happened if not for that failed experiment, if I didn't reach out and connect with my collaborators,” Blumberg reflects. At the end of the day, he says, the lesson is simple. “Don't give up. If you think about it, great science is necessary for great business—but great science does not necessarily equal great business. You might have great science, but if you're not solving an unmet need, or there's no market, then it's very hard to build a company. We're fortunate to be in that sweet spot of having great science and fulfilling an unmet need within a market.”