The U.S. Food and Drug Administration (FDA) today approved
Vitrakvi® (larotrectinib), the first ever oral TRK inhibitor, for
the treatment of adult and pediatric patients with solid tumors
that have a neurotrophic receptor tyrosine kinase (NTRK) gene
fusion without a known acquired resistance mutation, are metastatic
or where surgical resection is likely to result in severe
morbidity, and have no satisfactory alternative treatments or that
have progressed following treatment.1,2 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 confirmatory trials. Vitrakvi is the first treatment to
receive a tumor-agnostic indication at the time of initial FDA
approval. In clinical trials of patients with TRK fusion cancer,
Vitrakvi demonstrated an ORR of 75 percent (N=55) (95% CI, 61%,
85%), including a 22 percent complete response (CR) rate.2
“The FDA approval of larotrectinib marks an important milestone
in how we treat cancers that have an NTRK gene fusion – a rare
driver of cancer. I have seen firsthand how treatment with
larotrectinib, which is designed specifically for this oncogenic
driver, can deliver clinically meaningful responses in patients
with TRK fusion cancer, regardless of patient age or tumor type,”
said David Hyman, M.D., chief of the Early Drug Development Service
at Memorial Sloan Kettering Cancer Center and a global principal
investigator for a larotrectinib clinical trial. “We now have the
first therapy approved for this genomic alteration, regardless of
cancer type.”
NTRK gene fusions are genomic alterations that result in
constitutively-activated chimeric TRK fusion proteins that can act
as an oncogenic driver, promoting cell proliferation and survival
in tumor cell lines.2 Vitrakvi, developed by Bayer and Loxo
Oncology, Inc., is a CNS active TRK inhibitor designed to inhibit
these proteins.2 TRK fusions can be found in many types of solid
tumors and affect both children and adults.1 In the clinical trials
that were the basis for this approval, Vitrakvi showed clinical
benefit across numerous unique tumor types, including lung,
thyroid, melanoma, GIST, colon, soft tissue sarcoma, salivary gland
and infantile fibrosarcoma.2
“Today's approval of Vitrakvi is the culmination of years of
hard work and research by many people to bring the first ever
treatment to patients with TRK fusion cancer. TRK fusions are rare,
but occur across many different tumor types. In this era of
precision medicine, we are delivering on Bayer’s commitment to
advance the future of cancer care while providing value for
patients and physicians,” said Robert LaCaze, member of the
executive committee of Bayer’s Pharmaceuticals Division and head of
the Oncology Strategic Business Unit at Bayer. “It is very
rewarding to provide a therapy specifically for patients with
advanced solid tumors harboring an NTRK gene fusion.”
Vitrakvi® (larotrectinib) has warnings and precautions of
neurotoxicity, hepatotoxicity and embryo-fetal toxicity.2 The most
common adverse events observed in more than 20 percent of patients,
regardless of attribution, were increased ALT, increased AST,
anemia, fatigue, nausea, dizziness, cough, vomiting, constipation,
and diarrhea.2 The majority of adverse events occurring in greater
than or equal to 10 percent of patients were grade 1 or 2.2
TRK fusion cancer occurs across a broad range of tumor types
with varying frequency in both adult and pediatric patients.1 It is
diagnosed through the identification of NTRK gene fusions using
specific tests, including those that employ next-generation
sequencing (NGS) and fluorescence in situ hybridization
(FISH).2 Patients eligible for treatment with Vitrakvi should be
selected based on the presence of an NTRK gene fusion in their
tumor.2
“We are grateful to the investigators, research teams and
patients who contributed to and participated in the larotrectinib
clinical trials that supported this approval,” said Josh Bilenker,
M.D., chief executive officer of Loxo Oncology. “The approval of
Vitrakvi is a testament to the relentless prioritization of biology
in the drug development process. It is now even more critical to
screen patients of all ages with advanced solid tumors for
actionable genomic insights that could benefit their care or aid in
their referral to clinical trials.”
The FDA reviewed Vitrakvi under Priority Review, which is
reserved for medicines that could provide significant improvements
in the safety or effectiveness of the treatment for serious
conditions. The FDA previously granted Vitrakvi Breakthrough
Therapy Designation, Rare Pediatric Disease Designation and Orphan
Drug Designation.
“We welcome the FDA approval of Vitrakvi and the innovations in
genomic testing that make such precision medicine a reality,” said
Andrea Stern Ferris, president and chief executive officer of the
LUNGevity Foundation. “We’re seeing scientific advancements, like
genomic testing capable of detecting an NTRK gene fusion, beginning
to transform the treatment of cancer and provide new options for
patients.”
Vitrakvi will be available in oral capsules as well as a liquid
formulation for adults and children.2 For more information,
visit www.vitrakvi.com.
Bayer to Provide Comprehensive Value and Access
ProgramsBayer is committed to ensuring that patients in
the U.S. who are prescribed Vitrakvi are able to access the
medication and receive the support they may need. As part of this
commitment, Bayer is providing two comprehensive programs, the
Vitrakvi Commitment ProgramTM and the TRAK AssistTM patient support
program.
The Vitrakvi Commitment Program will refund the cost of Vitrakvi
to payers, patients and third-party organizations paying on behalf
of patients, in the event eligible patients do not experience
clinical benefit within 90 days of treatment initiation. Eligible
patients include those who have tested positive for an NTRK gene
fusion, have not received clinical benefit within 90 days of
treatment initiation, and received Vitrakvi from an in-network
specialty pharmacy.
The TRAK AssistTM patient support program provides comprehensive
reimbursement support and patient assistance services. For more
information and eligibility requirements, please call
1-844-634-TRAK (8725).
The Bayer US Patient Assistance Foundation, a charitable
organization that helps eligible patients get their Bayer
prescription medicine at no cost, is an additional resource for
patients in need of financial assistance.
“Express Scripts applauds Bayer for its thoughtful approach to
patient access. The Vitrakvi Commitment Program represents a
significant advance to patient access,” said Steve Miller, M.D.,
chief medical officer, Express Scripts. “We look forward to working
together to help those who will benefit from this medicine have
affordable access to it.”
Clinical Trial ResultsThe FDA approval of
Vitrakvi® (larotrectinib) is based on pooled data across the Phase
I adult trial, Phase II NAVIGATE trial and Phase I/II pediatric
SCOUT trial (N=55).2 In pooled study results, Vitrakvi demonstrated
an overall response rate (ORR) of 75 percent (95% CI, 61%, 85%) by
blinded independent review committee (with 22 percent of patients
achieving a complete response and 53 percent of patients achieving
a partial response) across various tumor types, including soft
tissue sarcoma, salivary gland, infantile fibrosarcoma, thyroid,
lung, melanoma, colon, GIST, cholangiocarcinoma, appendix, breast
and pancreas.2 Seventy-three percent of responding patients (N=41)
had a duration of response (DOR) lasting six months or greater at
the time of data cut-off.2 Median DOR (range 1.6+, 33.2+) and
progression-free survival (PFS) had not been reached at the time of
analysis.2,3 Median time to response was 1.84 months.3 In the
safety database (N=176), which included patients with and without
an NTRK gene fusion, the majority of adverse events (AEs) reported
in greater than or equal to 10 percent of patients were grade 1 or
2.2 AEs of any grade observed in more than 20 percent of patients,
regardless of attribution, included increased ALT (45%), increased
AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness
(28%), cough (26%), vomiting (26%), constipation (23%), and
diarrhea (22%).2 In October 2018, updated efficacy and safety data
on larotrectinib were presented at the ESMO 2018 Congress (European
Society for Medical Oncology).
Vitrakvi will be available in the U.S. market immediately. Bayer
submitted a Marketing Authorization Application (MAA) in the
European Union in August 2018.
For additional information about the larotrectinib clinical
trials, please refer to www.clinicaltrials.gov or
visit www.loxooncologytrials.com.
About Vitrakvi® (larotrectinib) Vitrakvi is an
oral TRK inhibitor for the treatment of adult and pediatric
patients with solid tumors with an NTRK gene fusion without a known
acquired resistance mutation that are either metastatic or where
surgical resection will likely result in severe morbidity, and have
no satisfactory alternative treatments or have progressed following
treatment.2 This indication is approved under accelerated approval
based on overall response rate and duration of response. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in confirmatory trials.
Research suggests that the NTRK genes can become abnormally fused
to other genes, producing a TRK fusion protein that can lead to the
growth and survival of solid tumors in various sites of the
body.1,2
In November 2017, Bayer and Loxo Oncology entered into an
exclusive global collaboration for the development and
commercialization of the TRK inhibitors larotrectinib and LOXO-195.
Bayer and Loxo Oncology are jointly developing the two products
with Loxo Oncology leading the ongoing clinical studies as well as
the filing in the U.S., and Bayer leading ex-U.S. regulatory
activities and worldwide commercial activities. In the U.S., Bayer
and Loxo Oncology will co-promote the products.
Larotrectinib has not been approved by the European Medicines
Agency.
About TRK Fusion CancerTRK fusion cancer occurs
when an NTRK gene fuses with another unrelated gene, producing an
altered TRK protein.2 The altered protein, or TRK fusion protein,
becomes constitutively active or overexpressed, triggering a
signaling cascade.2 These TRK fusion proteins act as oncogenic
drivers promoting cell growth and survival, leading to TRK fusion
cancer, regardless of where it originates in the body.2 TRK fusion
cancer is not limited to certain types of tissues and can occur in
any part of the body.1 TRK fusion cancer occurs in various adult
and pediatric solid tumors with varying frequency, including lung,
thyroid, GI cancers (colon, cholangiocarcinoma, pancreatic and
appendiceal), sarcoma, CNS cancers (glioma and glioblastoma),
salivary gland cancers (mammary analogue secretory carcinoma) and
pediatric cancers (infantile fibrosarcoma and soft tissue
sarcoma).1,2
Important Safety Information
Neurotoxicity: Among the 176 patients who
received VITRAKVI, neurologic adverse reactions of any grade
occurred in 53% of patients, including Grade 3 and Grade 4
neurologic adverse reactions in 6% and 0.6% of patients,
respectively. The majority (65%) of neurological adverse reactions
occurred within the first three months of treatment (range 1 day to
2.2 years). Grade 3 neurologic adverse reactions included delirium
(2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and
paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a
single patient. Neurologic adverse reactions leading to dose
modification included dizziness (3%), gait disturbance (1%),
delirium (1%), memory impairment (1%), and tremor (1%).2
Advise patients and caretakers of these risks with VITRAKVI.
Advise patients not to drive or operate hazardous machinery if they
are experiencing neurologic adverse reactions. Withhold or
permanently discontinue VITRAKVI based on the severity. If
withheld, modify the VITRAKVI dose when resumed.2
Hepatotoxicity: Among the 176 patients who
received VITRAKVI, increased transaminases of any grade occurred in
45%, including Grade 3 increased AST or ALT in 6% of patients. One
patient (0.6%) experienced Grade 4 increased ALT. The median time
to onset of increased AST was 2 months (range: 1 month to 2.6
years). The median time to onset of increased ALT was 2 months
(range: 1 month to 1.1 years). Increased AST and ALT leading to
dose modifications occurred in 4% and 6% of patients, respectively.
Increased AST or ALT led to permanent discontinuation in 2% of
patients.2
Monitor liver tests, including ALT and AST, every 2 weeks during
the first month of treatment, then monthly thereafter, and as
clinically indicated. Withhold or permanently discontinue VITRAKVI
based on the severity. If withheld, modify the VITRAKVI dosage when
resumed.2
Embryo-Fetal Toxicity: VITRAKVI can cause fetal
harm when administered to a pregnant woman. Larotrectinib resulted
in malformations in rats and rabbits at maternal exposures that
were approximately 11- and 0.7-times, respectively, those observed
at the clinical dose of 100 mg twice daily.2
Advise women of the potential risk to a fetus. Advise females of
reproductive potential to use an effective method of contraception
during treatment and for 1 week after the final dose of
VITRAKVI.2
Most Common Adverse Reactions (≥20%): The most
common adverse reactions (≥20%) were: increased ALT (45%),
increased AST (45%), anemia (42%), fatigue (37%), nausea (29%),
dizziness (28%), cough (26%), vomiting (26%), constipation (23%),
and diarrhea (22%).2
Drug Interactions: Avoid coadministration of
VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or
grapefruit juice), strong CYP3A4 inducers (including St. John’s
wort), or sensitive CYP3A4 substrates. If coadministration of
strong CYP3A4 inhibitors or inducers cannot be avoided, modify the
VITRAKVI dose as recommended. If coadministration of sensitive
CYP3A4 substrates cannot be avoided, monitor patients for increased
adverse reactions of these drugs.2
Lactation: Advise women not to breastfeed
during treatment with VITRAKVI and for 1 week after the final
dose.2
Please see the full Prescribing Information.
About Oncology at BayerBayer
is committed to delivering science for a better life by advancing a
portfolio of innovative treatments. The oncology franchise at
Bayer now includes five oncology products and several other
compounds in various stages of clinical development. Together,
these products reflect the company’s approach to research, which
prioritizes targets and pathways with the potential to impact the
way that cancer is treated.
About Bayer Bayer is a global
enterprise with core competencies in the Life Science fields of
health care and agriculture. Its products and services are designed
to benefit people and improve their quality of life. At the same
time, the Group aims to create value through innovation, growth and
high earning power. Bayer is committed to the principles of
sustainable development and to its social and ethical
responsibilities as a corporate citizen. In fiscal 2017, the Group
employed around 99,800 people and had sales of EUR 35.0 billion.
Capital expenditures amounted to EUR 2.4 billion, R&D expenses
to EUR 4.5 billion. For more information, go to www.bayer.us.
About Loxo OncologyLoxo Oncology is a
biopharmaceutical company focused on the development and
commercialization of highly selective medicines for patients with
genomically defined cancers. Our pipeline focuses on cancers that
are uniquely dependent on single gene abnormalities, such that a
single drug has the potential to treat the cancer with dramatic
effect. We believe that the most selective, purpose-built medicines
have the highest probability of maximally inhibiting the intended
target, with the intention of delivering best-in-class disease
control and safety. Our management team seeks out experienced
industry partners, world-class scientific advisors and innovative
clinical-regulatory approaches to deliver new cancer therapies to
patients as quickly and efficiently as possible. For more
information, please visit the company's website at
www.loxooncology.com.
© 2018 Bayer and Loxo Oncology, Inc. All rights reserved. Bayer,
the Bayer Cross and Vitrakvi are registered trademarks of Bayer and
Vitrakvi Commitment Program and TRAK Assist are trademarks of
Bayer.
Bayer Media Contact: Rose Talarico, Tel. +1
862.404.5302E-Mail: rose.talarico@bayer.com
Loxo Oncology, Inc. Contacts:Company: Lauren
CohenE-Mail: lcohen@loxooncology.com
Investors:Peter RahmerEndurance Advisors, LLCTel. +1
415.515.9763E-Mail: prahmer@enduranceadvisors.com
Media:Dan Budwick1AB MediaTel. +1 973-271-6085E-Mail:
dan@1abmedia.com
Forward-Looking Statements This press release
contains "forward-looking" statements within the meaning of the
safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. Forward-looking statements can be identified by
words such as: "anticipate," "intend," "plan," "goal," "seek,"
"believe," "project," "estimate," "expect," "strategy," "future,"
"likely," "may," "should," "will" and similar references to future
periods. These statements are subject to various known and unknown
risks, uncertainties and other factors that could cause actual
results to differ materially from what we expect. Examples of
forward-looking statements include, among others, statements we
make regarding the timing and success of Loxo Oncology’s clinical
trials or the collaboration between Bayer and Loxo Oncology, the
potential therapeutic benefits and economic value of larotrectinib
or other product candidates, and timing of future filings. Further
information on potential risk factors that could affect our
business and its financial results are detailed in Bayer's public
reports which are available on the Bayer website at www.bayer.com,
and Loxo Oncology’s most recent Quarterly Report on Form 10-Q, and
other reports as filed from time to time with the Securities and
Exchange Commission. Neither the Bayer Group or Loxo Oncology
undertakes any obligation to publicly update any forward-looking
statement, whether written or oral, that may be made from time to
time, whether as a result of new information, future developments
or otherwise.
References
- Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in
a new era of targeted therapy. Cancer Discov. 2015;5(1):25-34.
- Vitrakvi® (larotrectinib) capsules and solution for oral use
[Prescribing Information]. Stamford, CT: Loxo Oncology Inc.;
November 2018.
- Data on file, Stamford, CT: Loxo Oncology, Inc.; 2018.
LOXO ONCOLOGY, INC. (NASDAQ:LOXO)
Historical Stock Chart
From Jun 2024 to Jul 2024
LOXO ONCOLOGY, INC. (NASDAQ:LOXO)
Historical Stock Chart
From Jul 2023 to Jul 2024