Page 15 - HFA Dateline 2022 Special Edition

still be able to transmit hemophilia to risks over the long term,” Pipe said. “Anything that can safely and
their children,” Clark said. “And the last overarching aspiration effectively make a positive difference
for gene therapy is we want to be for quality of life is a good thing,”
Some researchers are trying to able to offer this to as many patients she said. “Our job is to help people
develop gene therapies that don’t use as possible. The reality is none of the understand what the risks and benefits
viruses to deliver the gene, according genetic therapies to date meet all are. Some people are going to be early
to Clark. “Some companies are using the check boxes for our aspirations adopters and some aren’t.”
nanoparticles, which are small particles yet. But there’s cause for optimism
made of fats or lipids,” he said. One critical consideration is that not
that the current wave of therapies is
Nanoparticle research is ongoing, really going to offer something worth everyone will be eligible for these
new treatments, Wilkes said. “Not
Clark added. “Nanoparticles are considering if they get approved by everyone will meet the criteria to
used now in mRNA vaccines for the regulators.” have gene therapy,” she added.
COVID-19,” he said, noting that Sonji Wilkes, vice president of public
using nanoparticles in gene therapy affairs for HFA, shares that optimism Among those who are ineligible are
for bleeding disorders poses a about gene therapy’s potential: those younger than 18, according to
particular challenge—getting the Pipe. “We don’t do this method of
factor-producing genes to the liver.
“Adeno-associated viruses naturally
target the liver,” Clark said. “But with Emerging Gene Therapies
nanoparticles, it’s going to be more of
for People With
a challenge to get them to the liver.”

Optimism and Concern Bleeding Disorders
Most people with bleeding disorders
can effectively manage their Several gene therapies are currently being tested in clinical trials in people
condition with current treatments. with moderately severe to severe hemophilia A and B. Data from some of
So what might make gene therapy these trials indicate that some gene therapies are showing promise.
a better option for some? “We have
well-established treatments and In the 134 participants with hemophilia A who participated in a Phase 3
protocols using factor-replacement GENEr8-1 clinical trial of Roctavian (valoctocogene roxaparvovec), a gene
therapy and now Hemlibra that are therapy from BioMarin Pharmaceutical Inc., results showed that participants
affording unprecedented bleed maintained therapeutic levels of factor VIII two years after dosing.
control and convenience for patients
and allowing them to live their lives Other gene therapies for hemophilia A currently in clinical trials include SPK-
to potential,” Pipe said. “With that 8011 from Spark Therapeutics (a member of the Roche Group) and SB-525
backdrop, what is gene therapy from Pfizer Inc. in collaboration with Sangamo Therapeutics Inc.
looking to achieve?” For 54 people with moderate to severe hemophilia B enrolled in the
Phase 3 HOPE-B clinical trial, a single dose of etranacogene dezaparvovec,
Pipe highlighted three achievements
he hopes gene therapy will deliver: a gene therapy from uniQure and CSL Behring that uses adeno-associated
sustained full restoration of blood virus 5 (AAV5), met its primary endpoint of reducing the annualized
coagulation, a way to deliver long- bleeding rate in participants when compared with factor IX prophylactic
term effective treatment without the therapy. The drug also increased endogenous factor IX activity and reduced
need for frequent infusions, and an the need for factor IX replacement therapy in participants.
acceptable ratio of treatment safety Another gene therapy for hemophilia B currently in a Phase 3 clinical trial is
to effectiveness. fidanacogene elaparvovec from Pfizer Inc. and Spark Therapeutics.

“Ideally, we want a genetic To learn more about gene therapy clinical trials for people with bleeding
therapy that is not going to have disorders, visit www.clinicaltrials.gov.
unacceptable toxicities or significant

Special Issue 2022 15