Page 14 - HFA Dateline 2022 Special Edition

However, he said, “We don’t really “Gene therapy has the potential to
know yet whether we can call it a
cure.” Clark said he expects that make a huge difference.” However,
some gene therapies now in clinical
trials may get regulatory approval “we don’t really know yet whether
and be licensed within the next we can call it a cure.”
couple of years. Currently, about
30 companies are working on —David Clark, PhD
hemophilia gene therapy.

A New Standard of Care? of corrective blood clotting with an The idea of injecting a virus into
To understand gene therapy’s injection weekly, or every two to four your body may sound scary. But
potential in changing treatment for weeks, Pipe said. adeno-associated viruses can’t make
people with bleeding disorders, it’s you sick. “They’re not active viruses
important to understand the current “What we’ve observed for patients anymore, and they don’t have any
standard of care. Today, prophylactic is that this has introduced a lot more genes that can make them active
therapy is the primary treatment to spontaneity into their lives,” he said. viruses,” Pipe said.
prevent bleeds, including repeated “They don’t have to think about their
joint bleeds that can lead to activities and their schedule linked to AAV vectors are coated with a
permanent joint damage. their prophylactic dosing as much as specific protein that encases the
they did when they were on traditional gene that produces FVIII or FIX (think
“For decades, it has been factor IV factor replacement. I think a lot of the gene as being wrapped in a
replacement therapy, and we have of patients and families have really package). Once the AAV particles
well-established treatments that afford enjoyed that spontaneity. But what reach the liver, the protein coat
protection from bleeds,” said Steven we haven’t been able to achieve with interacts with certain receptors on the
Pipe, MD, medical director of the any of these therapies is sustained full surface of the liver. The receptors tell
Pediatric Hemophilia and Coagulation restoration of blood coagulation.” the liver to accept the AAV, allowing
Disorders Program and medical the genes to reach the nucleus inside
director of the Special Coagulation Gene therapy could change that, each liver cell. Once there, liver cells
Laboratory at the University of according to Pipe. “What gene therapy help the genes to express and begin
Michigan in Ann Arbor. He noted that offers is a single infusion that would producing FVIII or FIX.
improvements in the half-life (the time provide long-term efficacy,” he said.
it takes for a drug to leave your body) “We put specific elements alongside
of factor replacement therapies have Gene Therapy Basics the FVIII and FIX gene so that it
reduced the frequency of IV infusions So how exactly does gene therapy will only be expressed in the tissue
for some people while still providing help people with bleeding disorders? that we want it to—in this case,
needed protection. “But the burden The gene therapies that are furthest the liver,” Pipe said. “These liver-
of frequency is still more than most along in clinical trials use an adeno- specific genetic elements are called
patients would like,” he said. associated virus (AAV) that targets promoters and enhancers. That way,
the liver. Depending on the drug type, even if the gene did get into non-liver
Since its approval by the U.S. Food researchers package the gene that cells, the gene would not express
and Drug Administration (FDA), makes FVIII or FIX into an AAV vector because the ‘machinery’ in the cell
emicizumab (Hemlibra)—the first (a vector is a living organism that acts would not recognize it.”
non-factor replacement therapy as a carrier). Then, they infuse the
for people with hemophilia—has altered AAV vector into the patient. It’s important to note that gene
changed prophy for some. With These particles enter the liver, where transfer, or gene therapy that delivers
its long half-life and ability to be the factor-making gene activates (a a working gene to help the body
delivered subcutaneously (under process known as expression). The produce FVIII or FIX, doesn’t affect
the skin) instead of through an IV, expressed gene tells the patient’s liver how bleeding disorders may be passed
patients can maintain a steady state to begin producing FVIII or FIX. to a person’s offspring. “Patients will

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