CLINICAL NEWS
Latest & Greatest
Oncology Community
Reacts to Medicare
Advantage’s “Step
Therapy” Decision
In early August 2018, the Centers for
Medicare and Medicaid Services (CMS)
announced it will allow Medicare Advan-
tage plans to implement “step therapy” for
drugs covered by Medicare Parts B and D.
Under the proposed changes, plans
will be permitted to require patients to
attempt a less expensive treatment option
before they can be prescribed a more ex-
pensive one. Medicare Advantage plans
administered by private health insurers
also could require that a cheaper Part B
therapy is used before a more expensive
Part B therapy.
The changes were implemented as
part of the Trump administration’s plan to
lower prescription drug prices by offering
Medicare an opportunity to negotiate bet-
ter deals for patients, according to CMS
Administrator Seema Verma, MPH. “It
may help [Medicare Advantage plans]
negotiate better discounts, encourage
drugmakers to lower costs, and encourage
patients to choose high-value medica-
tions,” she said.
The new policy would take effect in
January 2019, although details are still
scarce.
Patient groups, drug manufactur-
ers, and others have expressed skepti-
cism that step therapy would lower drug
prices or protect patients’ interests. Soon
after the decision was announced, more
than 90 medical societies, including
the American Society of Hematology,
co-signed a letter asking CMS to retain
a 2012 policy that prohibits these plans
from using step therapy.
“[Patients with cancer] should not
be forced to ‘fail first’ on a drug that is
known not to work for them before they
are allowed to take the recommended
treatment,” said Chris Hansen, presi-
dent of the American Cancer Society
Cancer Action Network, a co-signer of
the letter.
Drug manufacturers also voiced their
opposition. The Pharmaceutical Research
and Manufacturers of America (PhRMA)
said it has “serious concerns” with the new
policy, arguing that the program would
only delay access to needed medicines.
At least one advocacy group, though,
supported the changes. “I understand
[the concerns] because I have a disease
that will kill me if not treated correctly,”
said David Mitchell, president of Patients
for Affordable Drugs. “But if science says
ASHClinicalNews.org
drugs are equally effective, I’m okay start-
ing with the cheaper one.” something about how to treat human dis-
ease,” Dr. Lynch told The New York Times.
Sources: CMS memo, August 7, 2018; Reuters, August 7, 2018; The Hill,
August 9, 2018; Cancer Therapy Advisor, September 12, 2018. Sources: The New York Times, August 21, 2018. Vazquez JM, Sulak M,
Chigurupati S, Lynch VJ. A zombie LIF gene in elephants is upregulated
by TP53 to induce apoptosis in response to DNA damage. Cell Report.
2018;24:1765-76.
Elephants’ “Zombie
Gene” May Prevent
Cancer
Researchers have identified a gene that
appears to solve the mystery of why ele-
phants – who should be at a greater risk of
developing tumors because of their size –
are not more prone to cancer than smaller
animals. According to a report published
in Cell Reports by Vincent J. Lynch, PhD,
an evolutionary biologist at the University
of Chicago, and co-authors, the LIF6
gene works with the TP53 gene to protect
elephants against cancer development by
killing off damaged cells.
Researchers
believe the
discovery of the
LIF6 gene “might
tell us something
fundamental
about cancer as
a process.”
While all mammals carry a similar
gene, called LIF, it appears that only el-
ephants possess the LIF6 gene. This gene
became dormant through the course of
evolution, but researchers speculated that
it was “resurrected” when the ancestors
of living elephants evolved extra copies
of TP53.
The discovery of this “zombie gene”
builds on Dr. Lynch’s earlier research,
in which he recognized that elephants
have 20 copies of the TP53 gene.
(Comparatively, humans have only one
copy.) This “swarm” of TP53 copies
responds aggressively to DNA damage
by inducing the death of damaged cells
instead of repairing them.
The discovery of this gene, the re-
searchers noted, could provide inspiration
for developing new drugs. “It might tell us
something fundamental about cancer as a
process. And if we’re lucky, it might tell us
FDA Approves
Ibrutinib Combo
for Waldenström
Macroglobulinemia
The U.S. Food and Drug Administration
(FDA) approved ibrutinib, in combina-
tion with rituximab, for the treatment of
adult patients with Waldenström macro-
globulinemia (WM). In 2015, the agency
approved ibrutinib as a single agent for
this indication.
The most recent approval decision
was based on results from the phase III
iNNOVATE trial, which included 150
patients with treatment-naïve or relapsed
or refractory symptomatic WM. Patients
received rituximab, in combination with
either ibrutinib or a placebo, weekly for
four consecutive weeks, followed by a sec-
ond four-week course after three months.
In the group that received ibrutinib
plus rituximab, the rate of 30-month
progression-free survival was 82 percent,
compared with 28 percent in the placebo
group (p<0.0001). Ibrutinib plus ritux-
imab also resulted in a higher rate of
major response than rituximab treatment
(p<0.001).
Adverse events (AEs) that were more
common in the ibrutinib combination
arm than in the rituximab-alone arm
included atrial fibrillation and hyperten-
sion. AEs occurring more frequently in
the rituximab-alone arm included im-
munoglobin M flare and infusion-related
reactions.
Source: Janssen press release, August 27, 2018.
FDA Approves
New Treatment for
Hemophilia
The U.S. Food and Drug Administration
(FDA) approved BAY94-9027, or antihemo-
philic factor (recombinant), PEGylated-aucl,
for the prophylactic treatment of adults and
adolescents (≥12 years) with previously treat-
ed hemophilia A. The FDA also approved
the therapy for on-demand treatment and
the perioperative management of bleeding
in the same population.
The recombinant factor VIII replace-
ment therapy was approved based on
results from the phase II/III PROTECT
VIII trial of previously treated adults and
adolescents, which demonstrated bleed
protection and safety to a median of 1.9
years (range = 0-2.6 years).
The initial recommended prophylactic
regimen for BAY94-9027 is twice weekly,
with the ability to dose every five days and
individually adjust dosing based on bleed-
ing episodes.
The most frequently reported adverse
events were headache, cough, nausea,
and fever.
Sources: FDA approval letter, August 29, 2018; Bayer press release,
August 30, 2018.
Theranos Shutting
Down Amid Fraud
Allegations
In a letter to investors, the CEO of
Theranos announced that the blood-
testing company is preparing to shut down.
Theranos has faced a U.S. Securities and
Exchange Commission (SEC) investigation
and has already laid off most of its staff.
Founded by former CEO Elizabeth
Holmes, Theranos raised hundreds of
millions of dollars in private capital on the
promise that it could develop a revolu-
tionary new blood-testing technology that
could quickly and cheaply run dozens of
blood tests with just a few drops of blood.
A 2016 investigation by The Wall
Street Journal, however, raised concerns
about the company’s technology, finding
that Theranos was using routine blood-
testing equipment for most of its tests. As
questions about the technology emerged,
investors and federal regulators increased
their scrutiny of the company, leading
to a civil settlement between Theranos
and Ms. Holmes and the SEC in March
2018. The scandal is the subject of Bad
Blood: Secrets and Lies in a Silicon Valley
Startup, by John Carreyrou, which ASH
Clinical News Editor-in-Chief Mikkael
A. Sekeres, MD, MS, reviewed in his
October Editor’s Corner.
Both Ms. Holmes and former Theranos
president Ramesh Balwani are facing
criminal charges that could lead to years
in prison and millions of dollars in fines.
Prosecutors allege that Ms. Holmes and
Mr. Balwani deliberately misled investors,
regulators, and the public about the accu-
racy of the company’s technology. ●
Sources: The New York Times, September 5, 2018; The Associated Press,
September 5, 2018.
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