INDIANAPOLIS, Oct. 19, 2016 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) announced today that the U.S. Food and Drug
Administration (FDA) has granted approval of LARTRUVO™
(olaratumab injection, 10 mg/mL), in combination with doxorubicin,
for the treatment of adults with soft tissue sarcoma (STS) with a
histologic subtype for which an anthracycline-containing regimen is
appropriate and which is not amenable to curative treatment with
radiotherapy or surgery. LARTRUVO's indication is approved under
Accelerated Approval, and is based on data from the Phase 2 portion
of the pivotal JGDG trial. Continued approval for this indication
may be contingent upon verification and description of clinical
benefit in a confirmatory trial. LARTRUVO, in combination with
doxorubicin, is the first FDA-approved front-line therapy for STS
in four decades. The confirmatory Phase 3 trial, ANNOUNCE, is fully
enrolled.
"LARTRUVO represents an important step forward in soft tissue
sarcoma treatment," said William D. Tap, M.D., chief of the sarcoma
medical oncology services at Memorial Sloan Kettering Cancer Center
in New York and the principal
investigator of the JGDG registration trial. "We are pleased with
this approval, which will provide patients with a treatment option
that offers new hope in their battle against this difficult
disease."
Soft tissue sarcoma is a complex disease with multiple subtypes,
making it hard to diagnose and difficult to treat. For decades,
there have been no first-line therapeutic advancements for STS that
have improved overall survival (OS). According to the American
Cancer Society, in 2015, there were an estimated 12,000 new STS
cases diagnosed and nearly 5,000 deaths in the U.S. alone,
representing an unmet medical need.
LARTRUVO is the first monoclonal antibody approved to treat STS.
It also received Fast Track, Orphan Drug and Breakthrough Therapy
designations from the FDA for this indication, and was reviewed and
approved under the FDA's Accelerated Approval program. This program
allows for earlier approval of drugs that treat serious conditions
and that fill an unmet medical need.
"The approval of LARTRUVO is based on an encouraging and
positive study for patients, and represents progress in soft tissue
sarcoma treatment. For the first time in four decades, we now have
a combination regimen – LARTRUVO and doxorubicin – that offers
progress over doxorubicin alone in the front-line setting, by
improving overall survival for people with soft tissue sarcoma,"
said Richard Gaynor, M.D., senior
vice president, product development and medical affairs for Lilly
Oncology. "This continues our commitment to discovering new ways to
treat cancer, including for people who have rare types of
cancer."
"The entire sarcoma patient community is excited to have an
innovative medicine approved for the treatment of advanced soft
tissue sarcoma," said Bert E. Thomas
IV, PhD, MBA, CEO of the Sarcoma Foundation of America. "We
are confident that the approval of LARTRUVO may help these patients
live longer."
The approval of LARTRUVO is based on the results of JGDG, an
open-label, randomized, active-controlled study of 133 patients,
which compared LARTRUVO, in combination with doxorubicin
chemotherapy, to doxorubicin alone in patients with STS with a
histologic subtype for which an anthracycline-containing regimen
was appropriate and which is not amenable to curative treatment
with surgery or radiotherapy. The efficacy outcome measures were
OS, progression-free survival (PFS), and objective response rate
(ORR).
Median OS was improved by 11.8 months in patients randomized to
receive LARTRUVO plus doxorubicin compared to patients randomized
to doxorubicin alone, and was statistically significant. Median OS
was 26.5 months (95% CI: 20.9, 31.7) on the LARTRUVO-doxorubicin
arm compared to 14.7 months (95% CI: 9.2, 17.1) on the
doxorubicin-only arm (stratified hazard ratio [HR], 0.52; 95% CI:
0.34, 0.79, <0.05). The study met its prespecified
protocol-defined endpoint for PFS. Patients treated on the LARTRUVO
and doxorubicin arm achieved 8.2 months (95% CI: 5.5, 9.8) of
median PFS compared to 4.4 months (95% CI: 3.1, 7.4) on the
doxorubicin-only arm (stratified hazard ratio [HR], 0.74; 95% CI:
0.46, 1.19), based on independent review. The number of events at
the time of analysis was 37 (56%) on the LARTRUVO-doxorubicin arm
and 34 (51%) on the doxorubicin-only arm. The number of deaths at
the time of analysis was 39 (59%) on the LARTRUVO-doxorubicin arm
and 52 (78%) on the doxorubicin-only arm. Objective response rate
(ORR), based on independent review and defined as complete response
(CR) plus partial response (PR), was also assessed with an ORR of
18.2 percent (95% CI: 9.8, 29.6) (CR, 4.5%; PR, 13.6%) on the
LARTRUVO-doxorubicin arm and 7.5 percent (95% CI: 2.5, 16.6) (CR,
1.5%; PR, 6%) on the doxorubicin-only arm.
The labeling for LARTRUVO contains Warnings and Precautions for
infusion-related reactions and embryo-fetal toxicity. The most
commonly reported adverse reactions (all grades) occurring in ≥20
percent of patients receiving LARTRUVO plus doxorubicin versus
doxorubicin alone were nausea (73% vs 52%), fatigue (69% vs 69%),
musculoskeletal pain (64% vs 25%), mucositis (53% vs 35%), vomiting
(45% vs 19%), diarrhea (34% vs 23%) and headache (20% vs 9%). The
most common laboratory abnormalities (all grades) occurring in ≥20%
of patients receiving LARTRUVO plus doxorubicin versus doxorubicin
alone were lymphopenia (77% vs 73%), neutropenia (65% vs 63%),
thrombocytopenia (63% vs 44%), hyperglycemia (52% vs 28%), elevated
aPTT (33% vs 13%), hypokalemia (21% vs 15%) and hypophosphatemia
(21% vs 7%). Febrile neutropenia was reported in 13% of LARTRUVO
plus doxorubicin-treated patients versus 12% of doxorubicin-treated
patients.
Adverse reactions resulting in permanent discontinuation of
LARTRUVO occurred in 8% (5/64) of patients. The most common adverse
reaction leading to LARTRUVO discontinuation was infusion-related
reaction (3%). Dose reductions of LARTRUVO for adverse reactions
occurred in 25% (16/64) of patients; the most common adverse
reaction leading to dose reduction was Grade 3 or 4 neutropenia
(20%). Dose delays of LARTRUVO for adverse reactions occurred in
52% (33/64) of patients; the most common adverse reactions
resulting in dose delays were neutropenia (33%), thrombocytopenia
(8%) and anemia (5%). See the full Important Safety Information at
the end of this press release and the Prescribing
Information.
Lilly is committed to helping patients access LARTRUVO and
offers support programs for qualified uninsured, underinsured and
insured patients who receive LARTRUVO for its FDA-approved
indication and who may need assistance with their out-of-pocket
prescription medication costs, including a co-pay program where
qualified patients pay no more than $25 per infusion. Patients and healthcare
professionals with questions about LARTRUVO should contact The
Lilly Answers Center at 1-800-LillyRx (1-800-545-5979) or visit
www.lilly.com.
About LARTRUVO (olaratumab)
LARTRUVO is a platelet-derived growth factor receptor alpha
(PDGFR-α) blocking antibody that specifically binds PDGFR-α and
prevents receptor activation. LARTRUVO exhibits in vitro and
in vivo anti-tumor activity against selected sarcoma cell
lines and disrupted the PDGFR-α signaling pathway in in vivo
tumor implant models. Information about additional clinical trials
for LARTRUVO in sarcoma can be found at ClinicalTrials.gov (in the
search box on the home page, type in "olaratumab").
A Phase 3 trial of LARTRUVO and doxorubicin in advanced STS is
fully enrolled (ClinicalTrials.gov Identifier: NCT02451943).
About the JGDG Trial
JGDG was an open-label, randomized, active-controlled study that
compared LARTRUVO, in combination with doxorubicin chemotherapy, to
doxorubicin alone in patients with unresectable, soft tissue
sarcoma (STS).
The study enrolled 133 doxorubicin-naïve patients with STS with
a histologic subtype for which an anthracycline-containing regimen
was appropriate and which is not amenable to curative treatment
with surgery or radiotherapy. Sixty-six patients with an ECOG
performance status of 0 – 2 were randomized to the
LARTRUVO-doxorubicin arm and 67 to the doxorubicin-only arm.
Patients were randomized to receive LARTRUVO at 15 mg/kg as an
intravenous infusion on day one of each 21-day cycle in combination
with 75 mg/m2 doxorubicin, and LARTRUVO only on day
eight. Doxorubicin was administered following LARTRUVO infusion on
day one of each 21-day cycle for up to eight cycles. After
doxorubicin was discontinued, patients on the LARTRUVO plus
doxorubicin arm without evidence of disease progression or
unacceptable toxicity could continue to receive LARTRUVO
monotherapy until disease progression. All patients received the
cardioprotectant dexrazoxane prior to doxorubicin in cycles five to
eight.
About Sarcomas
Sarcomas are a diverse and relatively rare type of cancer that
usually develop in the connective tissue of the body, which include
fat, blood vessels, nerves, bones, muscles, deep skin tissues and
cartilage. Soft tissue sarcoma is a complex disease with multiple
subtypes, making it very hard to diagnose and difficult to treat.
For decades, there have been no front-line therapeutic advancements
for STS that have improved overall survival. According to the
American Cancer Society, in 2015, there were an estimated 12,000
new STS cases diagnosed and nearly 5,000 deaths in the U.S. alone.
INDICATION
LARTRUVO is indicated, in combination with doxorubicin, for the
treatment of adult patients with soft tissue sarcoma (STS) with a
histologic subtype for which an anthracycline-containing regimen is
appropriate and which is not amenable to curative treatment with
radiotherapy or surgery.
This indication is approved under Accelerated Approval.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the
confirmatory trial.
IMPORTANT SAFETY INFORMATION FOR LARTRUVO
Warnings and Precautions
Infusion-Related Reactions
- Infusion-related reactions (IRR) occurred in 70 (14%) of 485
patients who received at least one dose of LARTRUVO across clinical
trials. For 68 of these 70 patients (97%), the first occurrence of
IRR was in the first or second cycle. Grade ≥3 IRR occurred in 11
(2.3%) of 485 patients, with one (0.2%) fatality. Symptoms of IRR
included flushing, shortness of breath, bronchospasm, or
fever/chills, and in severe cases symptoms manifested as severe
hypotension, anaphylactic shock, or cardiac arrest.
Infusion-related reactions required permanent discontinuation in
2.3% of patients and interruption of infusion in 10% of patients.
All 59 patients with Grade 1 or 2 IRR
resumed LARTRUVO; 12 (20%) of these patients had a Grade 1 or
2 IRR with rechallenge. The incidence
of IRR in the overall safety database (N = 485) was similar (18%
versus 12%) between those who did (56%) and those who did not (44%)
receive premedication. Monitor patients during and following
LARTRUVO infusion for signs and symptoms of IRR in a setting with
available resuscitation equipment. Immediately and permanently
discontinue LARTRUVO for Grade 3 or 4
IRR.
Embryo-Fetal Toxicity
- Based on animal data and its mechanism of action, LARTRUVO can
cause fetal harm when administered to a pregnant woman. Animal
knockout models link disruption of platelet-derived growth factor
receptor alpha (PDGFR-α) signaling to adverse effects on
embryo-fetal development. Administration of an anti-murine PDGFR-α
antibody to pregnant mice during organogenesis caused malformations
and skeletal variations. Advise pregnant women of the potential
risk to a fetus. Advise females of reproductive potential to use
effective contraception during treatment with LARTRUVO and for 3
months after the last dose.
Most Common Adverse Reactions/Lab Abnormalities
- The most commonly reported adverse reactions (all grades; grade
3-4) occurring in ≥20% of patients receiving LARTRUVO plus
doxorubicin versus doxorubicin alone were nausea (73% vs 52%; 2% vs
3%), fatigue (69% vs 69%; 9% vs 3%), musculoskeletal pain (64% vs
25%; 8% vs 2%), mucositis (53% vs 35%; 3% vs 5%), alopecia (52% vs
40%; 0% vs 0%), vomiting (45% vs 19%; 0% vs 0%), diarrhea (34% vs
23%; 3% vs 0%) decreased appetite (31% vs 20%; 2% vs 0%), abdominal
pain (23% vs 14%; 3% vs 0%), neuropathy (22% vs 11%; 0% vs 0%), and
headache (20% vs 9%; 0% vs 0%).
- The most common laboratory abnormalities (all grades; grade
3-4) occurring in ≥20% of patients receiving LARTRUVO plus
doxorubicin versus doxorubicin alone were lymphopenia (77% vs 73%;
44% vs 37%), neutropenia (65% vs 63%; 48% vs 38%) and
thrombocytopenia (63% vs 44%; 6% vs 11%), hyperglycemia (52% vs
28%; 2% vs 3%), elevated aPTT (33% vs 13%; 5% vs 0%), hypokalemia
(21% vs 15%; 8% vs 3%), and hypophosphatemia (21% vs 7%; 5% vs
3%).
Use in Specific Populations
- Lactation: Because of the potential risk for serious adverse
reactions in breastfeeding infants, advise women not to breastfeed
during treatment with LARTRUVO and for at least 3 months following
the last dose.
For more information about LARTRUVO, please see full
Prescribing Information at
http://pi.lilly.com/us/lartruvo-uspi.pdf.
OR HCP ISI 19OCT2016
About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering
life-changing medicines and support to people living with cancer
and those who care for them. Lilly is determined to build on this
heritage and continue making life better for all those affected by
cancer around the world. To learn more about Lilly's commitment to
people with cancer, please visit www.LillyOncology.com.
About Eli Lilly and Company
Lilly is a global
healthcare leader that unites caring with discovery to make life
better for people around the world. We were founded more than a
century ago by a man committed to creating high-quality medicines
that meet real needs, and today we remain true to that mission in
all our work. Across the globe, Lilly employees work to discover
and bring life-changing medicines to those who need them, improve
the understanding and management of disease, and give back to
communities through philanthropy and volunteerism. To learn more
about Lilly, please visit us at www.lilly.com and
newsroom.lilly.com/social-channels. (P-LLY)
PP-OR-US-0078 10/2016 © Lilly USA, LLC 2016. ALL RIGHTS RESERVED.
LARTRUVO™ is a trademark owned by or licensed to
Eli Lilly and Company, its subsidiaries, or affiliates.
Lilly Forward-Looking Statement
This press release
contains forward-looking statements (as that term is defined in the
Private Securities Litigation Reform Act of 1995) about the
potential of LARTRUVO (olaratumab) as a treatment of advanced soft
tissue sarcoma, and reflects Lilly's current beliefs. However, as
with any pharmaceutical product, there are substantial risks and
uncertainties in the process of development and commercialization.
There can be no guarantee that future study results and patient
experience will be consistent with the study findings to date.
Among other things, there can also be no guarantee that LARTRUVO
will receive regulatory approval for any future indications or that
it will prove to be commercially successful. For further discussion
of these and other risks and uncertainties, see Lilly's most recent
Form 10-K and Form 10-Q filings with the United States Securities
and Exchange Commission. Except as required by law, Lilly
undertakes no duty to update forward-looking statements to reflect
events after the date of this release.
Refer to:
|
Karen Glowacki;
kglowacki@lilly.com; 317-370-1177 (media)
|
|
Philip L. Johnson;
philip_johnson_l@lilly.com; 317-748-1122 (investors)
|
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