CLINICAL NEWS
Latest & Greatest
FDA Approves
Ravulizumab for PNH
The U.S. Food and Drug Administration
(FDA) approved ravulizumab, a long-
acting complement inhibitor that prevents
hemolysis, for the treatment of adults with
paroxysmal nocturnal hemoglobinuria
(PNH).
The agency’s decision was based on
data from two clinical trials: In the first,
ravulizumab was noninferior to eculizum-
ab (the current standard of care for PNH)
in 246 patients with treatment-naïve
PNH, with similar proportions of patients
achieving transfusion-independence and
experiencing hemolysis. In the second, ra-
vulizumab was evaluated in a clinical trial
of 195 patients with PNH who had been
previously treated with eculizumab for at
least the past six months; patients were
randomized to either continue receiving
eculizumab or start treatment with ravu-
lizumab. Ravulizumab again was found to
be noninferior to eculizumab.
“The approval of [ravulizumab] will
change the way that patients with PNH
are treated,” said Richard Pazdur, MD,
director of the FDA’s Oncology Center
of Excellence and acting director of the
Office of Hematology and Oncology
Products in the FDA’s Center for Drug
Evaluation and Research. “Prior to this
approval, the only approved therapy for
PNH required treatment every two weeks,
which can be burdensome for patients and
their families. [Ravulizumab] uses a novel
formulation so patients only need treat-
ment every eight weeks, without compro-
mising efficacy.”
The most common adverse events
(AEs) associated with ravulizumab
included headache and upper respiratory
infection.
The prescribing information for
ravulizumab includes a boxed warning
about the risk of life-threatening menin-
gococcal infections and sepsis and also
advises health-care providers on menin-
gococcal vaccination and monitoring
for early signs of infection.
Ravulizumab was granted priority
review and orphan drug designations.
Source: FDA news release, December 21, 2018.
Tagraxofusp-erzs
Becomes First Approval
for BPDCN
The FDA approved tagraxofusp-erzs for
the treatment of adults and children (≥2
years of age) with blastic plasmacytoid
18
ASH Clinical News
dendritic cell neoplasm (BPDCN), mark-
ing the first approval for this rare disease.
The efficacy of tagraxofusp-erzs was
evaluated in two cohorts of patients in
a single-arm clinical trial. In the first
cohort, which included 13 patients with
untreated BPDCN, seven (54%) achieved
complete remission (CR) or CR with a
skin abnormality not indicative of active
disease (CRc); in the second cohort,
which included 15 patients with relapsed
or refractory BPDCN, one patient each
achieved CR and CRc.
Common AEs associated with
tagraxofusp-erzs included capillary leak
syndrome, nausea, fatigue, peripheral ede-
ma, pyrexia, chills, and weight increase.
The most commonly observed laboratory
abnormalities were decreases in lympho-
cytes, albumin, platelets, hemoglobin and
calcium, and increases in glucose and liver
enzymes. Given this observation, the ap-
proval letter advises health-care providers
to monitor patients’ liver enzyme levels.
Tagraxofusp-erzs was approved with
a boxed warning about the increased risk
of capillary leak syndrome, which may be
life-threatening or fatal.
This agent also was granted break-
through therapy, priority review, and
orphan drug designations.
Source: FDA news release, December 21, 2018.
Congress Passes
Bipartisan Sickle Cell Bill
The U.S. Congress recently passed the
Sickle Cell Disease and Other Heritable
Blood Disorders Research, Surveillance,
Prevention, and Treatment Act of 2018,
bipartisan legislation designed to improve
the lives of patients living with sickle cell
disease (SCD). The act includes provisions
for the following:
• authorizing public health initiatives
in SCD
• authorizing a SCD surveillance and
data collection program at the Centers
for Disease Control
• reauthorizing the existing SCD
Treatment Demonstration Program
at the Health Resources and Services
Administration
“Individuals with SCD not only suffer from
chronic, debilitating pain and are at risk for
other serious complications, but many of
them also lack access to the medical care
they need,” said Alexis A. Thompson, MD,
MPH, 2018 president of the American
Society of Hematology (ASH). “Expanding
efforts to better understand the prevalence
and treatment needs of people with this
disease, [this act] is the first step toward
understanding where gaps exist so groups
like ASH, policy-makers, and health-care
providers can address the need where it is
greatest.”
Sources: The Hill, December 11, 2018; ASH press release, December 11,
2018.
Dasatinib Granted
Approval for Pediatric
Indication
The FDA expanded the indication of
dasatinib, a second-generation tyrosine
kinase inhibitor, to include the treat-
ment of pediatric patients (≥1 year of
age) with newly diagnosed Philadelphia
chromosome (Ph)–positive acute lym-
phocytic leukemia (ALL).
The approval was based on results
from the phase II CA180-372 trial,
which enrolled 106 children with newly
diagnosed, Ph-positive ALL to received
dasatinib plus chemotherapy. Among the
78 patients who were evaluable for ef-
ficacy, the three-year event-free survival
rate was 64.1 percent.
Of the 81 patients included in the
safety analysis, three (4%) experienced
a grade 5 AE. Eight patients (10%)
experienced AEs leading to treatment
discontinuation, including fungal sepsis,
hepatotoxicity of graft-vs.-host disease,
thrombocytopenia, cytomegalovirus
infection, pneumonia, nausea, enteritis
and drug hypersensitivity. The most
common serious AEs (occurring in ≥10%
of patients) included pyrexia, febrile
neutropenia, mucositis, diarrhea, sepsis,
hypotension, and infections.
Dasatinib received priority-review
designation for this indication.
Source: Bristol-Myers Squibb press release, January 2, 2019.
Bristol-Myers Squibb
to Purchase Celgene
Bristol-Myers Squibb (BMS) agreed to
buy Celgene for $74 billion, making it the
second-biggest purchase in the pharma-
ceutical and biotechnology industry and
continuing a trend of large mergers and
buyouts in health care.
The merged company will have nine
products with more than $1 billion in
annual sales, including the myeloma
drug lenalidomide and the lung cancer
drug nivolumab. BMS also expects six
product launches over the next two years,
five of which will come from Celgene’s
pipeline; if approved, these products
will represent more than $15 billion in
potential revenue. However, shareholders
expressed concern that drugs in devel-
opment would not have enough sales to
offset major products losing exclusivity
between 2022 and 2026.
BMS said the buyout will lead to
$2.5 billion in cost savings by 2022,
mostly through cuts in sales, general,
and administrative expenses, as well as
reductions in research-and-development
spending. Conversely, the deal is expect-
ed to increase the company’s earnings
by more than 40 percent in the first year
after the deal closes.
BMS CEO and Chairman of the Board
Giovanni Caforio, MD, will continue to
serve in the same capacity for the com-
bined company.
Source: The Wall Street Journal, January 3, 2019.
FDA Updates Guidance
on Rare Disease Drug
Development
The FDA released a revised draft guidance
for sponsors developing “orphan drugs”
for the treatment or prevention of rare
diseases. The guidance, which is avail-
able for public comment through March,
updates the original draft guidance that
was published in 2015.
The revised document is intended to
assist industry sponsors in conducting
more efficient development programs,
including updated information about
natural history studies and the use of
biomarkers as surrogate endpoints.
“We know that developing a drug
or biologic for a rare disease can be
especially challenging, which is why it’s
important that the FDA continues to pro-
vide clear information to drug developers
so that they can plan modern, efficient
drug development programs that will
be successful,” said FDA Commissioner
Scott Gottlieb, MD. “Many of the up-
dates are in direct response to feedback
that we received on our prior draft.”
In its announcement of the draft
guidance, the agency noted that it plans to
hold a public meeting to obtain patients’
and caregivers’ perspectives on the effects
of rare diseases on their daily lives. This
information may help the FDA and spon-
sors better understand the diseases and
develop treatments for them through the
creation of novel endpoints or trial de-
signs that focus on commonalities across a
variety of rare diseases. ●
Source: FDA news release, January 16, 2019.
March 2019