THOUSAND OAKS, Calif.,
Jan. 9, 2022 /PRNewswire/
-- Amgen (NASDAQ: AMGN) today announced that the European
Commission (EC) has granted conditional marketing authorization for
LUMYKRAS® (sotorasib), a first-in-class
KRASG12C inhibitor, for the treatment of adults
with advanced non-small cell lung cancer (NSCLC) with KRAS
G12C mutation and who have progressed after at least one prior line
of systemic therapy. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
a confirmatory trial(s).
"The approval of LUMYKRAS, the first and only targeted therapy
for KRAS G12C-mutated NSCLC with proven efficacy, has the
potential to transform treatment outcomes for people in the
European Union living with this notoriously difficult-to-treat
cancer," said David M. Reese, M.D.,
executive vice president of Research and Development at Amgen.
"Amgen's landmark scientific discovery allowed investigators to
advance the first KRASG12C inhibitor into the
clinic, and we look forward to bringing this critical innovation to
more patients across the globe."
The EC decision follows the recommendation for approval by the
Committee for Medicinal Products for Human Use (CHMP) and is based
on the positive results from the Phase 2 CodeBreaK 100 clinical
trial in NSCLC, the largest trial conducted to date for patients
with the KRAS G12C mutation. LUMYKRAS 960 mg, administered
orally once-daily, demonstrated an objective response rate of 37.1%
(95% CI: 28.6-46.2) and a median duration of response (DoR) of 11.1
months. The most common adverse reactions were diarrhea (34%),
nausea (25%), and fatigue (21%). The most common severe
(grade ≥ 3) adverse reactions were increased alanine
aminotransferase level (ALT; 5%), increased aspartate
aminotransferase (AST; 4%), and diarrhea (4%).
NSCLC accounts for approximately 84% of the 2.2 million new lung
cancer diagnoses globally each year, including approximately
400,000 new cases in Europe
1,2 KRAS G12C is one of the most prevalent
driver mutations in NSCLC, with about 13-15% of European patients
with non-squamous NSCLC having the KRAS G12C
mutation.3,4 With EC approval, and subject to local
reimbursement applications, clinicians in all European Union member
countries, as well as Norway,
Iceland, and Liechtenstein, will be able to offer LUMYKRAS
to appropriate patients with NSCLC.
About
LUMAKRAS®/LUMYKRAS® (sotorasib)
Amgen took
on one of the toughest challenges of the last 40 years in cancer
research by developing LUMAKRAS/LUMYKRAS, a
KRASG12C inhibitor.5 LUMAKRAS/LUMYKRAS
has demonstrated a positive benefit-risk profile with rapid, deep
and durable anticancer activity in patients with locally advanced
or metastatic non-small cell lung cancer (NSCLC) harboring
the KRAS G12C mutation with a once daily oral
formulation.6
Amgen is progressing the largest and broadest global
KRASG12C inhibitor development program with
unparalleled speed and exploring more than 10 sotorasib combination
regimens, including triplets, with clinical trial sites spanning
five continents. To date, over 4,000 patients around the world have
received LUMAKRAS/LUMYKRAS through the clinical development program
and commercial use.
In May 2021, LUMAKRAS was the
first KRASG12C inhibitor to receive regulatory approval
anywhere in the world with its approval in the U.S., under
accelerated approval.
Regulatory approvals have also been received in the United Arab
Emirates (LUMAKRAS), Switzerland
(LUMYKRAS), and under the FDA's Project Orbis in Canada (LUMAKRAS)
and Great Britain (LUMYKRAS). Through Project Orbis, Amgen also has
Marketing Authorization Applications (MAAs) for sotorasib in review
in Australia, Brazil, Singapore and Israel. Additionally, Amgen has submitted MAAs
in Japan, South Korea, Turkey,
Taiwan, Colombia, Thailand, Mexico, Hong
Kong, Saudi Arabia,
Argentina, Kuwait and Qatar.
LUMAKRAS/LUMYKRAS is also being studied in multiple other solid
tumors.7
About Non-Small Cell Lung Cancer and
the KRAS G12C Mutation
Lung cancer is the
leading cause of cancer-related deaths worldwide, and it accounts
for more deaths worldwide than colon cancer, breast cancer and
prostate cancer combined.8 Overall survival rates
for NSCLC are improving but remain poor for patients with advanced
disease and 5-year survival is only 7% for those with
metastatic disease.9
KRAS G12C is the most
common KRAS mutation in
NSCLC.10 About 13% of patients with non-squamous
NSCLC harbor the KRAS G12C
mutation.4 Unmet medical need remains high and
treatment options are limited for NSCLC patients with
the KRAS G12C mutation whose first-line treatment
has failed to work or has stopped working. The outcomes with
current therapies are suboptimal with a median progression-free
survival of approximately 4 months following second-line treatment
of KRAS G12C-mutated NSCLC.11
About CodeBreaK
The CodeBreaK clinical development
program for Amgen's drug sotorasib is designed to study
patients with an advanced solid tumor with
the KRAS G12C mutation and address the
longstanding unmet medical need for these cancers.
CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label
multicenter study, enrolled patients
with KRAS G12C-mutant solid tumors.11
Eligible patients must have received a prior line of systemic
anticancer therapy, consistent with their tumor type and stage of
disease. The primary endpoint for the Phase 2 study was centrally
assessed objective response rate. The Phase 2 trial in NSCLC
enrolled 126 patients, 124 of whom had centrally evaluable lesions
by RECIST at baseline.7 The Phase 2 trial in colorectal
cancer (CRC) is fully enrolled and results have been submitted for
publication.12
CodeBreaK 200, the global Phase 3 randomized active-controlled
study comparing sotorasib to docetaxel in
KRAS G12C-mutated NSCLC completed enrollment of 345
patients. Eligible patients had previously treated,
locally-advanced and unresectable or metastatic
KRAS G12C-mutated NSCLC. The primary endpoint is
progression-free survival and key secondary endpoints include
overall survival, objective response rate, and patient-reported
outcomes.
Amgen also has several Phase 1b studies investigating sotorasib monotherapy
and sotorasib combination therapy across various advanced solid
tumors (CodeBreaK 101) open for enrollment. A Phase 2 randomized
study will evaluate sotorasib in patients with stage
IV KRAS G12C-mutated NSCLC in need of first-line
treatment (CodeBreaK 201).
For information, please
visit www.hcp.codebreaktrials.com.
Important EU/EEA Product Information
LUMYKRAS® (sotorasib) as monotherapy is
indicated for the treatment of adults with advanced non-small cell
lung cancer (NSCLC) with KRAS G12C mutation and who
have progressed after at least one prior line of systemic
therapy.
Important EU/EEA Safety information
This medicinal product is subject to additional
monitoring. This will allow quick identification of new safety
information. Healthcare professionals are asked to report any
suspected adverse reactions.
Contraindications
LUMYKRAS is contraindicated in patients with a history of
hypersensitivity to the active substance or to any of the
excipients.
Special Warning and Precautions for Use
Hepatotoxicity: Sotorasib can cause hepatotoxicity, which
may lead to drug-induced liver injury (DILI) and hepatitis.
Sotorasib has been associated with transient elevations of serum
transaminases (ALT and AST). These elevations improved or resolved
with dose modification or permanent discontinuation of treatment
and did not result in any cases of liver failure or fatal cases in
clinical studies. Among patients who experienced hepatotoxicity,
38% had hepatotoxicity leading to dose interruption or dose
reduction. Overall, 26% of patients with hepatotoxicity
received concurrent corticosteroids. Cases of liver enzyme increase
can be asymptomatic. Patients should be monitored for liver
function (ALT, AST, and total bilirubin) prior to the start of
LUMYKRAS, every 3 weeks for the first 3 months of
treatment, then once a month or as clinically indicated, with more
frequent testing in patients who develop transaminase and/or
bilirubin elevations. Based on the severity of the laboratory
abnormalities, treatment with LUMYKRAS must be stopped until
recovered to ≤ grade 1 or to baseline grade, and the dose
must either be modified or permanently discontinue treatment as
recommended (see section 4.2).
Interstitial Lung Disease (ILD)/pneumonitis:
ILD/pneumonitis occurred in patients treated with LUMYKRAS with
prior exposure to immunotherapy or radiotherapy (see
section 4.8). Monitor patients for new or worsening pulmonary
symptoms indicative of ILD/pneumonitis (e.g. dyspnoea, cough,
fever). Immediately withhold LUMYKRAS in patients with suspected
ILD/pneumonitis and permanently discontinue LUMYKRAS if no other
potential causes of ILD/pneumonitis are identified (see
section 4.2).
Lactose intolerance: LUMYKRAS contains lactose. Patients
with rare hereditary problems of galactose intolerance, total
lactase deficiency or glucose–galactose malabsorption should not
take this medicinal product.
Adverse Reactions
The most common adverse reactions were diarrhoea (34%), nausea
(25%) and fatigue (21%). The most common severe adverse reactions
were increased alanine aminotransferase (ALT) (5%), increased
aspartate aminotransferase (AST) (4%), and diarrhoea (4%). The most
common adverse reactions leading to permanent discontinuation of
treatment were increased ALT (1%) and increased AST (1%) and
drug-induced liver injury (1%). The most common adverse reactions
leading to dose modification were increased ALT (6%), diarrhoea
(6%), increased AST (6%), nausea (3%), increased blood alkaline
phosphatase (3%) and vomiting (2%).
LUMAKRAS® (sotorasib) U.S. Indication
LUMAKRAS is indicated for the treatment of adult patients
with KRAS G12C-mutated locally advanced or
metastatic non-small cell lung cancer (NSCLC), as determined by an
FDA-approved test, who have received at least one prior systemic
therapy.
This indication is approved under accelerated approval based on
overall response rate (ORR) and duration of response (DOR).
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial(s).
LUMAKRAS® (sotorasib) Important U.S. Safety
Information
Hepatotoxicity
- LUMAKRAS can cause hepatotoxicity, which may lead to
drug-induced liver injury and hepatitis.
- Among 357 patients who received LUMAKRAS in CodeBreaK 100,
hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A
total of 18% of patients who received LUMAKRAS had increased
alanine aminotransferase (ALT)/increased aspartate aminotransferase
(AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose
interruption or reduction, 5% of patients received corticosteroids
for the treatment of hepatotoxicity.
- Monitor liver function tests (ALT, AST and total bilirubin)
prior to the start of LUMAKRAS every 3 weeks for the first 3 months
of treatment, then once a month or as clinically indicated, with
more frequent testing in patients who develop transaminase and/or
bilirubin elevations.
- Withhold, dose reduce or permanently discontinue LUMAKRAS based
on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis
- LUMAKRAS™ can cause ILD/pneumonitis that can be fatal. Among
357 patients who received LUMAKRAS™ in CodeBreaK 100,
ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade
3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued
due to ILD/pneumonitis in 0.6% of patients.
- Monitor patients for new or worsening pulmonary symptoms
indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever).
Immediately withhold LUMAKRAS in patients with suspected
ILD/pneumonitis and permanently discontinue LUMAKRAS if no other
potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions
- The most common adverse reactions ≥ 20% were diarrhea,
musculoskeletal pain, nausea, fatigue, hepatotoxicity and
cough.
Drug Interactions
- Advise patients to inform their healthcare provider of all
concomitant medications, including prescription medicines,
over-the-counter drugs, vitamins, dietary and herbal products.
- Inform patients to avoid proton pump inhibitors and
H2 receptor antagonists while taking
LUMAKRAS™.
- If coadministration with an acid-reducing agent cannot be
avoided, inform patients to take LUMAKRAS™ 4 hours before or 10
hours after a locally acting antacid.
Please see LUMAKRAS full Prescribing
Information.
About Amgen Oncology
At Amgen Oncology,
our mission to serve patients drives all that we do. That's why
we're relentlessly focused on accelerating the delivery of
medicines that have the potential to empower all angles of care and
transform lives of people with cancer.
For the last four decades, we have been dedicated to discovering
the firsts that matter in oncology and to finding ways to reduce
the burden of cancer. Building on our
heritage, Amgen continues to advance the largest pipeline
in the Company's history, moving with great speed to advance those
innovations for the patients who need them.
At Amgen, we're advancing oncology at the speed of
life®.
For more information, follow us
on www.twitter.com/amgenoncology.
About Amgen
Amgen is committed to unlocking the
potential of biology for patients suffering from serious illnesses
by discovering, developing, manufacturing and delivering innovative
human therapeutics. This approach begins by using tools like
advanced human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages
its biologics manufacturing expertise to strive for solutions that
improve health outcomes and dramatically improve people's lives. A
biotechnology pioneer since 1980, Amgen has grown to be the world's
largest independent biotechnology company, has reached millions of
patients around the world and is developing a pipeline of medicines
with breakaway potential.
Amgen is one of the 30 companies that comprise the Dow Jones
Industrial Average and is also part of the Nasdaq-100 index.
In 2021, Amgen was named one of the 25 World's Best Workplaces™ by
Fortune and Great Place to Work™ and one of the 100 most
sustainable companies in the world by Barron's.
For more information, visit www.amgen.com and follow us on
www.twitter.com/amgen.
Forward-Looking Statements
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forward-looking statements that are based on the current
expectations and beliefs of Amgen. All statements, other than
statements of historical fact, are statements that could be deemed
forward-looking statements, including any statements on the
outcome, benefits and synergies of collaborations, or potential
collaborations, with any other company (including BeiGene, Ltd.,
Kyowa-Kirin Co., Ltd., or any collaboration to manufacture
therapeutic antibodies against COVID-19), the performance of
Otezla® (apremilast) (including anticipated Otezla sales
growth and the timing of non-GAAP EPS accretion), the Five Prime
Therapeutics, Inc. acquisition, or the Teneobio, Inc. acquisition,
as well as estimates of revenues, operating margins, capital
expenditures, cash, other financial metrics, expected legal,
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practices, customer and prescriber patterns or practices,
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information as of the date of this news release and does not
undertake any obligation to update any forward-looking statements
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events or otherwise.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project. Our results
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Furthermore, our research, testing, pricing, marketing and other
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Further, while we routinely obtain patents for our products and
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CONTACT: Amgen, Thousand
Oaks
Megan Fox, 805-447-1423 (media)
Michael Strapazon, 805-313-5553
(media)
Arvind Sood, 805-447-1060
(investors)
*LUMAKRAS, LUMYKRAS, and Advancing Oncology at The Speed of Life
are trademarks of Amgen Inc.
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