FEATURE
studies were performed in men,” Dr. George explained. “How-
ever, AAV vectors are being used to treat other conditions
in women, so I think it’s feasible that it could be extended to
female patients in the future.”
While some “early adopters” will likely jump on board for
gene therapy, Dr. Pasi said, others will take the “wait-and-see”
approach as researchers learn more about the products’ long-
term safety and durability. “The history of hemophilia makes for
a very conservative population,” he noted.
He also said that gene therapy is being explored in develop-
ing countries. “We currently are looking at gene therapy through
the prism of use in the developed world, but those with arguably
the most to gain from a one-off treatment are those who cannot
access standard treatments or who live in places where factor
replacement regimens are impractical for various reasons,” he
explained. —By Debra L. Beck ●
”If we can achieve
predictable and
durable expression,
then, theoretically, this
approach could help
everyone.” —LINDSEY A. GEORGE, MD
REFERENCES
1. Naso MF, Tomkowicz B, Perry WL, Strohl WR. Adeno-associated virus (AV) as a vector
for gene therapy. BioDrugs. 2017;31:317-34.
2. Meisbach W, Meijer K, Coppens M, et al. Gene therapy with adeno-associated viral
vector 5-human factor IX in adults with hemophilia B. Blood. 2018;131:1022-31.
3. Sullivan SK, George LA, Ragni MV, et al. SPK-8011: preliminary results from a phase
1/2 trial of investigational gene therapy for hemophilia confirm transgene derived
increases in FVIII activity that are persistent and stable beyond eight months. Mol
Ther. 2018;26(suppl):350.
4. George LA, Sullivan SK, Giermasz A, et al. Hemophilia B gene therapy with a high-
specific-activity factor IX variant. N Engl J Med. 2017;377:2215-27.
5. Rangarajan S, Walsh L, Lester W, et al. N Engl J Med. 2017;377:2519-30.
6. U.S. Food and Drug Administration. FDA approves novel gene therapy to treat patients
with a rare form of inherited vision loss. Accessed September 6, 2018, from https://
www.fda.gov/newsevents/newsroom/pressannouncements/ucm589467.htm.
7. BioMarin Pharmaceuticals press release. Accessed September 6, 2018, from http://
investors.biomarin.com/2018-05-22-BioMarin-Provides-2-Years-of-Clinical-Data-in-
6e13-vg-kg-Dose-from-Ongoing-Phase-1-2-Study-in-Valoctocogene-Roxaparvovec-
Gene-Therapy-for-Severe-Hemophilia-A-at-World-Federation-of-Hemophilia-2018-
World-Congress.
8. National Hemophilia Foundation. Fast facts about bleeding disorders. Accessed
September 6, 2018, from https://www.hemophilia.org/About-Us/Fast-Facts.
Dr. High suggested the possibility of identifying which
patients are most likely to “buy into” the promise of gene ther-
apy by looking at those who have opted to enroll in the trials.
These include older individuals who have developed other
medical problems and don’t want to have to worry about their
hemophilia anymore. “We have also seen many younger people
volunteer for trials,” she added. “These are people who resent
the so-called ‘brutal discipline of prophylaxis.’ They want to
live their lives without being reminded several times a week
that they’re different.”
SIDEBAR
A Bargain, Even at Seven Figures
Manufacturers have yet to offer clear intentions on pricing,
but even at seven figures, gene therapy may be a bargain if it
can offset years of costly prophylaxis. Although none of the
experts who spoke with ASH Clinical News could offer any solid
information on pricing, the talk among analysts is that these
products could top $1 million for a single infusion.
The cost of a year’s worth of recombinant product can run
as high as $300,000 per year, not accounting for potential
complications. 1 On top of that, the disease incurs tremendous
indirect and intangible costs from diminished work productiv-
ity, absenteeism, and reduced quality of life.
“Even if [manufacturers] charge $1 million, that would be a
great deal,” said Express Scripts Chief Medical Officer Steve Miller,
MD, in a recent interview with Reuters. “So, there are going to be
some gene therapies where it is very clear that everyone who has
that disease should get it.” 2
In a recent economic analysis published in Blood Advances,
researchers indicated that gene therapy for severe hemophilia
18
Focus on Classical Hematology
A would still be cost-effective at a price of $1 million, compared
with standard factor VIII prophylaxis. They estimated that, with
gene therapy, patients would gain 8.33 quality-adjusted life
years (QALYs) over a 10-year horizon, compared with 6.62 QALYs
for standard therapy. 3
The model also assumed a success rate of 90 percent with
gene therapy, which is lower than what has been reported in
phase I and II trials. “I think this paper is a nice summary, albeit
from a developed world perspective and with the financial cave-
ats that that would entail,” John Pasi, MBChB, PhD, commented.
REFERENCES
1. Chen SL. Economic costs of hemophilia and the impact of prophylactic treatment
on patient management. Am J Manag Care. 2016;22 (5 Suppl):s126-33.
2. Reuters. Express scripts staking out million-dollar gene therapies. Accessed
September 6, 2018, from https://www.reuters.com/article/us-expressscripts-
genetherapy/express-scripts-staking-out-million-dollar-gene-therapies-
idUSKBN1L00EE.
3. Machin N, Ragni MV, Smith KJ. Gene therapy in hemophilia A: a cost-effectiveness
analysis. Blood Adv. 2018;2:1792-98.