CLINICAL NEWS
days of andexanet alfa administration in
33 of 185 patients (17.8%) evaluable for
safety in the ongoing ANNEXA-4 study.
Because of this thromboembolic risk, the
FDA labeling advises clinicians to monitor
patients for signs and symptoms of these
events and to resume anticoagulation as
soon as medically appropriate following
andexanet treatment.
The approval comes after long delays in
the review of andexanet’s biologics license
application: In December 2017, the FDA
extended the BLA review for the second
time, after the drug’s manufacturer, Portola
Pharmaceuticals, submitted additional data
from the ANNEXA-4 study.
immune systems. The FDA directed the
U.S. Marshals Service to seize supplies
of the vaccine and is now ordering the
center and its founders to cease marketing
unapproved products and to correct its
manufacturing violations.
“Cell-based regenerative medicine
holds significant medical opportunity,
but we’ve also seen some bad actors le-
verage the scientific promise of this field
to peddle unapproved treatments that
put patients’ health at risk,” said FDA
Commissioner Scott Gottlieb, MD. “In
[these two cases], the clinics and their
leadership have continued to disregard
the law and, more importantly, patient
safety. We cannot allow unproven prod-
ucts that exploit the hope of patients and
their loved ones.”
in scope,” said Craig Garthwaite, PhD,
director of the Health Enterprise Manage-
ment Program at Northwestern Univer-
sity’s Kellogg School of Management. “The
proposal is vague on details and filled with
more slogans than actual sound economic
policies.”
data from two single-center, random-
ized, open-label studies (EPOE-12-02
and EPOE-14-01) that established the
pharmacodynamic and pharmacokinetic
data of epoetin alfa-epbx 100 u/kg as a
single dose or multiple doses in healthy
participants. In each trial, the biosimilar
met prespecified acceptance criteria for
similarity with its reference product.
The most common AEs associated with
epoetin alfa-epbx and its reference product
include hypertension, joint pain, muscle
spasm, fever, dizziness, medical-device
malfunction, and blood-vessel blockage.
As with epoetin alfa, the biosimilar carries
a boxed warning about increased risk of
death, heart problems, stroke, and tumor
growth or recurrence. Additional warn-
ings include high blood pressure, seizures,
aplastic anemia, serious allergic reactions,
and severe skin reactions.
The FDA’s drug-
pricing blueprint
outlines changes
to “correct
the abuses of
FDA Cracks Down on
the system
Unapproved Stem-Cell
that impede
Trump
Administration
Clinics
competition.”
Reveals Plans to
FDA Expands
The FDA filed complaints in May seeking
permanent injunctions against two stem-
Daratumumab’s
“While some of these proposals could
cell clinics, U.S. Stem Cell Clinic of Sunrise, Lower Drug Prices
help make medicines more affordable for
Florida and the California Stem Cell
In May, President Donald Trump and
Indication to Frontline
patients, others would disrupt coverage
Treatment Center, as part of a comprehen-
members of his administration outlined
and limit patients’ access to innovative
sive approach to overseeing regenerative
plans to lower prescription drug prices:
Myeloma Treatment
treatments,” the pharmaceutical industry’s
medicine products.
First, the president unveiled initiatives to
Source: Portola Pharmaceuticals, Inc. press release, May 3, 2018.
Sources: FDA news release, May 9, 2018; The New York Times, May 9, 2018.
Source: FDA news release, May 15, 2018.
“[These clinics]
have continued
to disregard the
law and, more
importantly,
patient safety.”
—SCOTT GOTTLIEB, MD
In the case of U.S. Stem Cell Clinic,
the FDA is seeking a permanent injunc-
tion against the company, its chief
scientific officer, and its co-owner and
managing officer for marketing unap-
proved products for the treatment of a
variety of diseases, including Parkinson’s
disease, amyotrophic lateral sclerosis,
chronic obstructive pulmonary disease,
heart disease, and pulmonary fibrosis.
The clinic also engaged in improper
manufacturing practices, including
some that could impact the sterility of
their products. The company failed to
address and correct previous violations
outlined by the FDA in a warning letter
sent in August 2017.
When sending that letter, the agency
also learned that the California Stem Cell
Treatment Center was administering a
commercially smallpox vaccine to cancer
patients with potentially compromised
ASHClinicalNews.org
remove barriers to generic-drug devel-
opment and spur competition among
pharmaceutical companies.
The FDA simultaneously released a
blueprint outlining changes the agency
would take to “correct the abuses of the
system that impede competition.” Pro-
posed actions would require foreign gov-
ernments to pay more for drugs created
as a result of U.S. innovation and would
force drugmakers to publicize list prices in
their direct-to-consumer advertising. The
blueprint includes more than 50 initia-
tives, but critics noted that few of them
would entail immediate changes.
Three days later, Department of Health
and Human Services (HHS) Secretary
Alex Azar announced a series of actions
the department would take to change
the way Medicare and Medicaid pay for
prescription drugs and how the FDA ap-
proves products. His most ambitious plan
is to ban pharmacy benefit managers from
negotiating discounts and rebates with
drug manufacturers and replace the pro-
cess with contracts based on a set price.
Mr. Azar also wants to simplify how
Medicare pays for drugs by moving
expensive medications administered in-
office (like anti-cancer medications) into
the standard Medicare Part D program,
through which private health insurance
companies can negotiate discounts with
drug companies.
Following President Trump’s speech,
drug-pricing experts who spoke with
The Wall Street Journal questioned the
effectiveness of these proposed efforts.
“Overall, this is quite underwhelming
trade group PhRMA said in a statement
responding to the speech. According to
The Wall Street Journal, shares of drug
stocks rose after the president’s speech:
Merck & Co. increased 2.8 percent and
Regeneron Pharmaceuticals jumped 6.2
percent.
Sources: The Wall Street Journal, May 11, 2018; FDA news release, May 11,
2018; NPR, May 14, 2018.
First Biosimilar for
Anemia Treatment
Approved by FDA
Epoetin alfa-epbx, a biosimilar to epoetin
alfa, was approved for the treatment of
anemia caused by chronic kidney disease,
chemotherapy, or use of zidovudine in pa-
tients with HIV infection. The biosimilar,
like its reference product, also is indicated
for use before and after surgery to reduce
the need for red blood–cell transfusions
due to blood loss.
The agency voted to approve epoetin
alfa-epbx after a review of its structural
and functional characteristics, animal-
study data, human pharmacokinetic and
pharmacodynamic data, clinical immuno-
genicity data, and other clinical safety and
effectiveness data – all of which demon-
strate that the product is biosimilar to its
reference product. In its approval notice,
the FDA stressed that epoetin alfa-epbx
is approved as a biosimilar and not as an
interchangeable product.
The decision was supported by
The FDA approved a new indication for
the anti-CD38 monoclonal antibody
daratumumab, to include the treatment
of patients who are newly diagnosed with
myeloma and ineligible for autologous
hematopoietic cell transplantation.
In the frontline setting, daratumumab
is indicated for combination treatment
with bortezomib, melphalan, and predni-
sone (VMP). This is the fifth indication for
daratumumab, which is already approved
for the treatment of patients with relapsed
or refractory myeloma.
The decision was supported by data
from the randomized, open-label, multi-
center phase III ALCYONE trial, which
was presented as a late-breaking abstract
at the 2017 ASH Annual Meeting. In the
trial, treatment with the daratumumab
combination reduced the risk of disease
progression or death by 50 percent,
compared to treatment with VMP alone
(hazard ratio [HR] = 0.50; 95% CI 0.38-
0.65; p<0.001). The median progression-
free survival (PFS) for the daratumumab
combination was not reached, while PFS
in the VMP-alone arm was 18.1 months
(p value not provided).
In the ALCYONE trial, the most
frequent AEs (>20%) in the daratumumab
arm included upper respiratory–tract
infection (48% vs. 28% in the VMP-alone
arm), infusion reactions (28% vs. 0%), and
peripheral edema (21% vs. 14%). ●
Sources: Janssen press release, May 8, 2018; Mateos MV, Dimopoulos
MA, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and
prednisone for untreated myeloma. N Engl J Med. 2018;378:518-28.
ASH Clinical News
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