THOUSAND OAKS, Calif.,
Jan. 20, 2022 /PRNewswire/ -- Amgen
(NASDAQ: AMGN) today announced that LUMAKRAS®
(sotorasib) has been approved in Japan for the treatment of KRAS
G12C-mutated positive, unresectable, advanced and/or recurrent
non-small cell lung cancer (NSCLC) that has progressed after
systemic anticancer therapy.
"Today's approval of LUMAKRAS as the first and only
KRASG12C inhibitor marks a paradigm shift in the
treatment of patients with non-small cell lung cancer in
Japan," said David M. Reese, M.D., executive vice president
of Research and Development at Amgen. "In just over three years
since the first patient was dosed in the pivotal CodeBreaK 100
trial, LUMAKRAS is now approved in nearly 40 countries,
illustrating our commitment to accelerating transformative
medicines for patients living with cancers that have yet to be
fully addressed."
The approval by the Japan Ministry of Health, Labour and Welfare
(MHLW) is based on 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. Based on the approved
label in Japan, LUMAKRAS 960 mg,
orally administered once-daily, demonstrated an objective response
rate (ORR) of 37% (95% CI: 28.8-46.6) in 123 evaluable patients
(including 10 Japanese patients* with a data cutoff date:
Sept. 1, 2020). Adverse
reactions were observed in 128 (67%) of 190 patients†
(including 13 Japanese patients). The most common adverse reactions
(incidence ≥ 5%) were diarrhea (28%), nausea, increased alanine
aminotransferase (ALT) and increased aspartate
aminotransferase (AST) (16% each), fatigue (11%), increased blood
alkaline phosphatase (8%), vomiting (7%) and abdominal pain
(5%).
Results from the Phase 2 CodeBreaK clinical trial in NSCLC were
published in The New England Journal of Medicine.
"KRAS gene mutations are one of the oldest known cancer
driver gene mutations," said Steve
Sugino, president and representative director, Amgen K.K.
"However, it has proven to be very difficult to develop drugs for
the treatment of KRAS gene mutations. For nearly 40 years,
researchers have said that the mutation was 'undruggable.' I am
very pleased that LUMAKRAS is now approved as a new treatment
option for patients in Japan."
"The prognosis for patients with non-small cell lung cancer who
have distant metastases or whose disease has relapsed after
surgery, is generally poor," said Tetsuya Mitsudomi, M.D.,
professor, Department of Surgery, Division of Thoracic Surgery at
Kindai University School of Medicine, past-president of the
International Association for the Study of Lung Cancer (IASLC) and
past-president of the Japan Lung Cancer Society (JLCS). "Recent
developments in molecular-targeted drugs and immunotherapy have
dramatically improved the prognosis for these patients. However,
despite the relatively high frequency of the KRAS G12C
mutation, no drugs specifically targeting this mutation have been
available until recently. Therefore, the approval of LUMAKRAS in
Japan is a major milestone in the
treatment of non-small cell lung cancer patients with KRAS
G12C mutations."
On March 11, 2021, the MHLW
designated sotorasib as an orphan drug.
*3 subjects (including 1 Japanese subject) without measurable
lesions at baseline as determined by the central review were
excluded.
†Patients with non-small cell lung cancer who received
at least 1 dose of this drug 960 mg in the phase I and II
parts.
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.1 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.2
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. LUMAKRAS/LUMYKRAS® is also
approved in the United Arab
Emirates, the European Union and Switzerland, and in Canada and Great
Britain under the FDA's Project Orbis. 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 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.3
About Non-Small Cell Lung Cancer and
the KRAS G12C Mutation
Lung cancer is the second most prevalent cancer in the world, and
the total number of patients in Japan is estimated to be about
169,000.4,5 Lung cancer is also the leading cause of
cancer site-specific mortality worldwide and in Japan, with an estimated 82,300 deaths
annually.5 About 85-90% of lung cancer patients are
classified as having NSCLC (such as adenocarcinoma, squamous cell
carcinoma, and large cell carcinoma).6 NSCLC is a
life-threatening, serious disease, and the 5-year survival rate of
patients with stage IV NSCLC in Japan is 10.8% for adenocarcinoma and 2.7% for
squamous cell carcinoma, indicating that the prognosis of this
disease is still poor.7
KRAS G12C is the most common KRAS mutation in
NSCLC.8 KRAS G12C mutation is reported to be
found in approximately 13% of lung adenocarcinoma in the
U.S. and 4.5% of non-squamous cell carcinoma in Japan.9,10 There is a significant
unmet need as there are limited treatment options for patients with
NSCLC harboring KRAS G12C mutations who have failed or lost
response to first-line treatment. Outcomes with available therapies
have been suboptimal, with median progression-free survival after
second-line therapy reported to be approximately 4 months in
patients with NSCLC harboring KRAS G12C
mutations.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.2,3
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.2 The Phase 2 trial in colorectal
cancer (CRC) is fully enrolled and results have been
published.11
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 Japan Product information
Product
Name:
|
LUMAKRAS®
TABLETS 120 mg
|
Generic
Name:
|
sotorasib
|
Indication:
|
KRAS G12C
mutated, unresectable, advanced and/or recurrent non-small cell
lung cancer that has progressed after systemic anticancer
therapy
|
Precautions related to
indications:
|
- The product should
be administered to patients who are confirmed as KRAS
G12C-mutated by a pathologist with adequate experience or by
testing at a testing facility. Approved in vitro diagnostics should
be used for the testing. List of the approved in vitro diagnostics
is available on the following website.
https://www.pmda.go.jp/review-services/drug-reviews/review-information/cd/0001.html
- Physicians should
select patients to be treated with the product based on their good
understanding of the "17. Clinical Studies" section of the package
insert, and of the efficacy and safety of the product, with careful
consideration of the use of therapies other than the
product.
- The efficacy and
safety of the product in the first-line therapy have not been
established.
- The efficacy and
safety of the product in postoperative adjuvant therapy have not
been established.
|
Dosage and
Administration:
|
The usual adult dosage
is 960 mg of sotorasib administered orally once daily. The dose may
be reduced according to the patient's condition.
|
Please refer to the latest package insert for
details.
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.
Amgen K.K.
Amgen K.K. is the Japanese subsidiary of Amgen Inc., the largest
independent biotechnology company in the world. In October 2013, we began our business as Amgen
Astellas BioPharma, a joint venture with Astellas Pharma. On
April 1, 2020, we became a wholly
owned subsidiary of Amgen and changed our trade name. Amgen K.K.
focuses on areas with high unmet medical needs, including
cardiovascular disease, cancer, bone disease,
inflammatory/immunologic disease, and neurological disease. With
our mission "To serve patients – everything we can do now"
approximately 600 employees are engaged in everything from clinical
development to marketing.
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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based on the current expectations and beliefs of Amgen. All
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including any statements on the outcome, benefits and synergies of
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collaboration to manufacture therapeutic antibodies against
COVID-19), the performance of Otezla® (apremilast)
(including anticipated Otezla sales growth and the timing of
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No forward-looking statement can be guaranteed and actual
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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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