CLINICAL NEWS
Latest & Greatest
for the measurement of minimal residual
disease (MRD) in patients with acute
lymphocytic leukemia (ALL) or multiple
myeloma (MM). This is the first NGS-
based test approved for this purpose.
The FDA’s approval was based on re-
sults from a retrospective analysis of three
separate studies comprising 273 patients
with ALL, 323 patients with MM, and 706
patients with MM, respectively. In patients
with ALL, negative MRD results detected
by the ClonoSEQ assay were correlated
with higher event-free survival rates; in
patients with MM, negative results were
associated with higher progression-free
and disease-free survival rates (p values
not provided).
The ClonoSEQ assay identifies and
quantifies gene sequences extracted from
patient DNA and can measure MRD
down to 1 in 1 million cells (<10 -6 ), while
previously available methods measured
MRD via flow cytometry or polymerase
chain reaction–based assays down to 1 in
10,000 (<10 -4 ) or 1 in 100,000 cells (<10 -5 ).
The FDA reviewed the ClonoSEQ as-
say through the de novo premarket review
pathway, which is designed for novel, low-
to moderate-risk devices of a new type.
“Having a highly sensitive test avail-
able to measure MRD in [patients with]
ALL or MM can help providers man-
age their patients’ care,” FDA Commis-
sioner Scott Gottlieb, MD, said in a press
release announcing the approval. “The
FDA is applying novel regulatory ap-
proaches to make sure that these rapidly
evolving NGS tests are accurate and reli-
able. At the same time, we’re seeing more
and more laboratory-developed tests seek
marketing authorization from the FDA.
… We believe that to more fully unlock
these innovations, we need to modernize
the regulatory framework for all in vitro
clinical tests.”
Source: FDA press release, September 28, 2018.
FDA Approves Once-
Weekly Carfilzomib
Combo for Relapsed or
Refractory MM
The FDA has approved a combination
of once-weekly carfilzomib with dexa-
methasone for the treatment of patients
with relapsed or refractory multiple
myeloma (MM). This is the third ap-
proved indication for the proteasome
inhibitor carfilzomib, which previously
received approval as a single agent and
in combination with dexamethasone or
with dexamethasone plus lenalidomide
in this patient population.
The agency’s approval is based on
results from the randomized phase III
ARROW trial, which included 478 patients
40
ASH Clinical News
with relapsed or refractory MM who had
received two or three prior therapies. Par-
ticipants were randomly assigned to receive
either a 30-minute infusion of once-weekly
carfilzomib 70 mg/m 2 with dexamethasone
or a 10-minute infusion of twice-weekly
carfilzomib 27 mg/m 2 with dexamethasone.
Patients receiving the once-weekly
treatment had longer progression-free
survival compared with the twice-weekly
cohort (11.2 months vs. 7.6 months,
respectively; p=0.0014). The overall
response rates were 62.9 percent and 40.8
percent in the once-weekly and twice-
weekly arms, respectively (p<0.0001).
The most common adverse events
in either arm of the ARROW trial were
anemia, diarrhea, fatigue, hypertension,
insomnia, and pyrexia.
Source: Amgen press release, October 1, 2018.
Generics
Manufacturers and
Consumer Advocates
Criticize Revamped
NAFTA Deal
The recently updated North American Free
Trade Agreement, now known as the U.S.-
Mexico-Canada Agreement (USMCA),
includes a 10-year exclusivity period for
biologics, which is drawing criticism from
generic drug manufacturers and consumer
advocates. The policy is designed to protect
drug manufacturers that invest in research
and development, but these groups are
concerned that the measure will have
a harmful effect on the development of
biosimilars.
Under the agreement, generic drug
manufacturers would be prohibited from
producing biosimilars – which often
provide cheaper alternatives to biologic
agents – during the reference products’
10-year exclusivity period. Although the
USMCA shortens the 12-year exclusiv-
ity period mandated by U.S. law, patient
groups and generics manufacturers argue
that the deal will make it difficult to
reduce the exclusivity period in the future,
potentially impeding the government’s
ability to lower drug costs by encouraging
the development of biosimilars.
“The revised rules would further strain
health-care budgets, contribute to people’s
suffering and family financial hardship,
and most likely cost people their lives,”
said Peter Maybarduk, from the consumer
advocacy group Public Citizen, in a state-
ment. “Their purpose is to better insulate
expensive new medicines from generic
competition, helping pharmaceutical cor-
porations keep the prices of at least some
new medicines higher for longer.”
USMCA also creates marketing
exclusivity periods for new uses and new
forms of existing medicines, as well as
new combinations of older medicines.
Under the agreement, patents also could
be granted for new uses and methods for
an existing drug.
“The revised
rules would
further strain
health-care
budgets,
contribute
to people’s
suffering and
family financial
hardship, and
most likely cost
people their
lives.”
—PETER MAYBARDUK
While the three nations have commit-
ted to the agreement, formal ratification
and implementation are pending.
Source: STAT News, October 1, 2018.
FDA Approves New
Hemophilia A Drug
The FDA has approved emicizumab-kxwh
as prophylaxis to prevent or reduce the
frequency of bleeding episodes in adult
and pediatric patients with hemophilia A
with or without factor VIII (FVIII) inhibi-
tors. The drug was first approved in 2017
for patients with hemophilia A with FVIII
inhibitors.
The approval also provided new dos-
ing regimens for these patients.
The agency’s approval is based on
results from the phase III HAVEN 3 and
HAVEN 4 clinical trials. In the HAVEN 3
study, 89 adults and adolescents with
hemophilia A without factor VIII in-
hibitors received either no prophylactic
treatment or prophylactic treatment
with emicizumab-kxwh 1.5 mg/kg
once weekly or 3 mg/kg once every two
weeks. The weekly and biweekly arms
experienced 96-percent and 97-percent
reductions in their annualized bleed
rates (ABRs) for treated bleeds, respec-
tively, compared with the control group
(p<0.0001).
In the single-arm HAVEN 4 trial,
48 adult and adolescent patients with
hemophilia A with and without FVIII
inhibitors were treated with prophylactic
emicizumab-kxwh 6 mg/kg once every
four weeks for at least 24 weeks. The ABR
for treated bleeds was 2.4 and the median
ABR was zero (range = 0-2.08).
Common adverse events occurring in
both trials included injection-site reac-
tions, headache, and joint pain. The pre-
scribing information includes a warning
that patients should be monitored for the
development of thrombotic microangi-
opathy and thrombotic events if activated
prothrombin complex concentrate is
administered.
Source: FDA news release, October 4, 2018.
New Bill Bans
Pharmacist Gag Orders
Congress has passed two bills prohibit-
ing “gag clauses” in contracts between
pharmacies and insurance companies
or pharmacy benefit managers (PBMs).
The legislation – one for Medicare and
Medicare Advantage beneficiaries and the
other for employer-based and individual
policies – received widespread bipartisan
support in both houses of Congress.
Gag clauses in pharmacy contracts
prevent pharmacists from informing
patients when the out-of-pocket cost of
a prescription drug is the same or lower
than what they would pay for the drug
through their insurance plan. However,
neither piece of legislation requires
pharmacists to inform consumers of
cheaper options; the patient is respon-
sible for asking about the less-expensive
option.
The bill governing commercial
insurance plans is effective immediately;
the Medicare and Medicare Advantage
bill will take effect on January 1, 2020.
Consumer advocates and trade
organizations, though supportive of the
legislation, predicted that it would have
limited impact, emphasizing that while
the ban on gag clauses will likely reduce
overpayment for pharmaceuticals, it
does not address the root cause of high
drug costs.
“As a country, we’re spending about
$450 billion on prescription drugs annu-
ally,” said Steven Knievel of consumer
advocacy group Public Citizen in a state-
ment to Kaiser Health News. The money
saved by banning gag clauses, he said,
“is far short of what needs to happen to
actually deliver the relief people need.”
Sources: Kaiser Health News, October 10, 2018; The Washington Post,
October 10, 2018.
Continued on page 42
December 2018