ASH Clinical News ACN_4.13_full issue_Web | Page 61

FEATURE
paid by the plan to the PBM for a drug is
greater than the amount paid by the PBM
to the pharmacy, the PBM retains that
difference.
PBMs also often coordinate a network
of pharmacies that distribute the drug, add-
ing another layer of complexity. Pharmacies
earn most of their revenue from fees from
insurance companies to dispense the drugs
and a smaller portion from rebate payments
from drug manufacturers.
The pharmacy does “play a role in
pricing, sometimes direct and some-
times indirect,” said Dr. Lakdawalla. “The
pharmacy wants a piece of the ‘price pie’
and puts upward pressure to get the pie
to be as large as possible.” Meanwhile, the
insurance companies and employers who
purchase insurance plans want the lowest
price possible, he added. PBMs, though,
can benefit both from higher list prices
and by bringing them down.
“No one quite knows what kind of
rebates PBMs receive, so it’s difficult to de-
termine whether PBMs are actually helping
to lower drug prices,” Dr. Lakdawalla said.
Negotiation Tactics
During discussions between the drug maker
and the PBMs (and, in turn, the insurance
companies), the drug maker frequently ne-
gotiates for its pharmacy-dispensed drug to
be placed on the insurance plan’s preferred
In the INO-VATE ALL study, more patients achieved MRD-negative complete
remission and proceeded to HSCT after CD22-directed treatment with BESPONSA 1,2
Median OS in patients treated with BESPONSA was 7.7 months (95% CI, 6.0-9.2) vs
6.2 months (95% CI, 4.7-8.3) in patients treated with SC (HR=0.75; P=0.0105). b The analysis
of OS did not meet a prespecifi ed boundary for statistical signifi cance of P=0.0104. 1,2
The most common (≥2%) serious adverse events were infection (23%), febrile neutropenia (11%),
hemorrhage (5%), abdominal pain (3%), pyrexia (3%), VOD (2%), and fatigue (2%) 1,2
Study design: INO-VATE ALL was a Phase 3, open-label, randomized (1:1) study of BESPONSA vs investigator’s choice of SC in 326 adult patients with relapsed
or refractory B-cell precursor ALL. SC included FLAG, HiDAC, or Ara-C + MXN. All patients were required to have ≥5% bone marrow blasts and to have
received 1 or 2 previous induction chemotherapy regimens for ALL. Patients with Ph+ B-cell precursor ALL were required to have failed treatment with ≥1 TKI
and SC. Single-agent BESPONSA was given by 1-hour IV infusion in 3 fractionated doses at 1.8 mg/m 2 each 3- to 4-week cycle, reduced to 3 fractionated doses
at 1.5 mg/m 2 per cycle after achieving CR/CRi, for up to 6 cycles. For patients proceeding to HSCT, the recommended treatment duration with BESPONSA is
2 cycles. Patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment. 1,3
Ara-C + MXN=cytarabine + mitoxantrone; CI=confi dence interval; CR=complete remission; CRi=CR with incomplete hematologic recovery; FLAG=fl udarabine, Ara-C,
and granulocyte colony-stimulating factor; HiDAC=high-dose cytarabine; HR=hazard ratio; HSCT=hematopoietic stem cell transplant; MRD=minimal residual disease;
OS=overall survival; Ph+=Philadelphia chromosome–positive; SC=standard chemotherapy; TKI=tyrosine kinase inhibitor; VOD=hepatic veno-occlusive disease.
Response assessments were performed in the fi rst 218 patients randomized, and survival analyses were completed in the full study population of 326 patients.
a
1-sided P value using chi-square test.
b
1-sided P value using log-rank test.
Learn more at BesponsaHCP.com
Infusion-Related Reactions: Infusion-related reactions (all Grade 2) were
reported in 4/164 patients (2%). Premedicate with a corticosteroid, antipyretic,
and antihistamine prior to dosing. Monitor patients closely during and for
at least 1 hour after the end of the infusion for the potential onset of
infusion-related reactions including symptoms such as fever, chills, rash,
or breathing problems. Interrupt the infusion and institute appropriate
medical management if an infusion-related reaction occurs. Depending
on the severity, consider discontinuation of the infusion or administration
of steroids and antihistamines. For severe or life-threatening infusion
reactions, permanently discontinue BESPONSA.
QT Interval Prolongation: Increases in QT interval corrected for heart rate
using Fridericia’s formula of ≥ 60 msec from baseline were measured in
4/162 patients (3%). Administer BESPONSA with caution in patients who
have a history of or predisposition to QTc prolongation, who are taking
medicinal products that are known to prolong QT interval, and in patients
with electrolyte disturbances. Obtain electrocardiograms and electrolytes
prior to treatment and after initiation of any drug known to prolong QTc,
and periodically monitor as clinically indicated during treatment.
Embryo-Fetal Toxicity: BESPONSA can cause embryo-fetal harm. Apprise
pregnant women of the potential risk to the fetus. Advise males and
females of reproductive potential to use effective contraception during
BESPONSA treatment and for at least 5 and 8 months after the last
dose, respectively. Advise women to contact their healthcare provider
if they become pregnant or if pregnancy is suspected during treatment
with BESPONSA.
Adverse Reactions: The most common ( ≥ 20%) adverse reactions observed
with BESPONSA were thrombocytopenia, neutropenia, infection, anemia,
leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia,
transaminases increased, abdominal pain, gamma-glutamyltransferase
increased, and hyperbilirubinemia. The most common ( ≥ 2%) serious adverse
reactions were infection, febrile neutropenia, hemorrhage, abdominal pain,
pyrexia, VOD, and fatigue.
Nursing Mothers: Advise women against breastfeeding while receiving
BESPONSA and for 2 months after the last dose.
INDICATION
BESPONSA is indicated for the treatment of adults with relapsed or
refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Please see brief summary of full Prescribing Information, including
BOXED WARNING, on adjacent pages.
References: 1. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
2. Data on fi le. Pfi zer Inc, New York, NY. 3. Kantarjian HM, DeAngelo DJ, Stelljes M,
et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic
leukemia. N Engl J Med. 2016;375(8):740-753.
PP-INO-USA-0183-03
© 2018 Pfi zer Inc.
All rights reserved.
April 2018
drug list, making it more likely to be
used by patients. But, these negotiating
tactics work best for competitive classes
of drugs, like insulin products for diabe-
tes, Ms. Kaltenboeck explained. Rebates
in hematology and oncology remain
relatively low.
Within the health-care market, how
much an insurance company pays for a drug
varies substantially, with some companies
getting a better deal than others, according