Breaking News
April 26, 2019 - Porvair Sciences’ ultra-flat Krystal glass bottom microplates for imaging applications
April 26, 2019 - Medicines Discovery Catapult’s Virtual R&D Discovery Services platform announce twenty-two partnerships
April 26, 2019 - How optimism can bias prognosis in serious illness
April 26, 2019 - Hospitals Chafe Under Medicare’s New Payment Rule For Off-Campus Clinics
April 26, 2019 - New drug minimizes damage after a heart attack by 60 percent
April 26, 2019 - Synthesizing Modified and Pharmaceutically Relevant Peptides
April 26, 2019 - Using blood thinners in heart failure patients associated with reduced risk of thromboembolic events
April 26, 2019 - Study finds different amounts of physical therapy for stroke patients
April 26, 2019 - Psychologists study how application of cortisol affects exposure therapy for anxiety disorders
April 26, 2019 - SibFU scientists create multilayer gilded nanodisks for medical applications
April 26, 2019 - Marking the start of Pediatric Sepsis Week
April 26, 2019 - The Inflamed Brain | NIH News in Health
April 26, 2019 - Stress-free training may enhance surgical skill
April 26, 2019 - Newsom: California Leads On Prescription Drugs
April 26, 2019 - Exploring novel strategies to heal damage after a heart attack
April 26, 2019 - Small army of tiny robots can remove dental plaque
April 26, 2019 - Cellular communication in emotion-processing brain region motivates us to keep eating tasty food
April 26, 2019 - Greater spousal life satisfaction associated with lower mortality risk
April 26, 2019 - Genetic mutations in brain development lead to discovery of rare genetic diseases
April 26, 2019 - Speech-Based Algorithm Helps ID Posttraumatic Stress Disorder
April 26, 2019 - First birth via robot-assisted uterus transplant
April 26, 2019 - Studies verify novel method of HIV transmission among injection drug users and effective prevention
April 26, 2019 - CircRNAs bind to dsRNA-activated protein kinase which is linked to innate immunity
April 26, 2019 - MR Solutions wins third Queen’s Award
April 26, 2019 - Study details how optimism can bias prognosis in serious illness
April 26, 2019 - Vascular surgery after firearm injury linked with higher morbidity and mortality
April 26, 2019 - New findings about aggressive blood cancer may help develop drugs with less harmful side effects
April 26, 2019 - People with intense feelings of responsibility susceptible to developing OCD, anxiety
April 26, 2019 - Despite expansion of insurance coverage for depression, treatment rates are lower than expected
April 26, 2019 - Huge Malaria vaccine trial in Malawi
April 26, 2019 - Can Obesity Shrink Your Brain?
April 26, 2019 - This oral appliance could help you (and your partner) sleep better
April 26, 2019 - Myelination deficits cause abnormal hypersocial behavior associated with Williams syndrome
April 26, 2019 - New sepsis detector uses photonics to make accurate diagnosis in less than thirty minutes
April 26, 2019 - New study describes process to diagnose rare genetic diseases in record time
April 26, 2019 - Scientists and patients gather in Vancouver to discuss about Stevens-Johnson syndrome
April 26, 2019 - Advance in breakthrough cancer treatment eliminates serious side effects
April 26, 2019 - Discovery about cold sensing could pave way for new pain relief drugs
April 26, 2019 - Children often turn to sugary drinks instead of water
April 26, 2019 - Genome analysis shows the combined effect of many genes on cognitive traits
April 26, 2019 - Patients Caught In Middle Of Fight Between Health Care Behemoths
April 26, 2019 - Drug overdoses among adolescents and young adults on the rise
April 26, 2019 - Implementing a Paperless QC Micro Laboratory”
April 25, 2019 - Obesity linked to a reduction in gray matter
April 25, 2019 - Smart assistants could help combat opioid crisis
April 25, 2019 - Diagnostic stewardship strategy reduces inappropriate testing
April 25, 2019 - Three-antibiotic cocktail eradicates ‘persister’ Lyme bacteria in mouse model
April 25, 2019 - Study investigates how early blindness shapes sound processing
April 25, 2019 - Outcomes Worse for Cancer Patients Seen at Noncancer EDs
April 25, 2019 - Link found between temperament of high-risk infants and obesity
April 25, 2019 - Al Letson explores ties between journalists and doctors at Medicine and the Muse symposium
April 25, 2019 - New mobile phone game can detect people at risk of Alzheimer’s
April 25, 2019 - Scientists discover trigger region for absence epileptic seizures
April 25, 2019 - Stretchy wearable patch can do a health check while you work out
April 25, 2019 - Exercise activates brain circuits associated with memory in older adults
April 25, 2019 - Veggies, Fruits and Grains Keep Your Heart Pumping
April 25, 2019 - Healthy meal kits can boost children’s long-term health
April 25, 2019 - Designing an inexpensive surgical headlight: A Q&A with a Stanford surgeon
April 25, 2019 - States Weigh Banning A Widely Used Pesticide Even Though EPA Won’t
April 25, 2019 - Integrator complex proteins are crucial for healthy brain development in fruit flies, study finds
April 25, 2019 - Device converts brain signals into speech, offering hope for patients
April 25, 2019 - Measles vaccination rates are a ‘public health time bomb’
April 25, 2019 - Maths made easier for scientists students who shun the subject wins award
April 25, 2019 - Researchers decode how cancer drug works in brains of Parkinson’s disease patients
April 25, 2019 - Smarter Brain Cancer Trial Comes to Columbia
April 25, 2019 - Researchers Seek Sage Advice Of Elders On Aging Issues
April 25, 2019 - New chemical synthesis strategy leads to identification of novel, simpler derivatives
April 25, 2019 - Vanderbilt investigators discover link between vascular biology and eye disease
April 25, 2019 - Feces transplantation is effective and provides economic benefits
April 25, 2019 - Eisenhower Health first in Southern California to offer new lung valve treatment for COPD/emphysema
April 25, 2019 - Johns Hopkins researchers uncover role of neurotransmitter in the spread of aggressive cancers
April 25, 2019 - Porvair Sciences offers highly effective P3 microplate for biological sample clean-up
April 25, 2019 - Air pollution increases risk for respiratory hospitalization among childhood cancer survivors
April 25, 2019 - We are sitting more! How bad is that?
April 25, 2019 - Majority of stroke survivors not screened for osteoporosis, despite increased risk
April 25, 2019 - ADHD Screening: MedlinePlus Lab Test Information
April 25, 2019 - Cellular alterations increase vulnerability of obese and diabetic individuals to infection
April 25, 2019 - Association Insurance Pushes On Despite Court Ruling
April 25, 2019 - Traditional and e-cigarette users may be more receptive to smoking cessation interventions
April 25, 2019 - Delving into tumor’s cellular lineage may offer clues for customized therapies
FDA Approves Lenvima (lenvatinib) for First-line Treatment of Unresectable Hepatocellular Carcinoma (HCC)

FDA Approves Lenvima (lenvatinib) for First-line Treatment of Unresectable Hepatocellular Carcinoma (HCC)

image_pdfDownload PDFimage_print

Woodcliff Lake, NJ and Kenilworth, NJ, Aug. 16, 2018 – Eisai Inc. and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) approved the kinase inhibitor Lenvima (lenvatinib) for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). This approval was based on results from REFLECT (Study 304), where Lenvima demonstrated a proven treatment effect on overall survival (OS) by statistical confirmation of non-inferiority, as well as statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS) and objective response rate (ORR) when compared with sorafenib in patients with previously untreated unresectable HCC.

“Unresectable hepatocellular carcinoma is an extremely difficult-to-treat cancer, with no new first-line systemic therapy options for more than a decade,” said Dr. Ghassan Abou-Alfa, medical oncologist, Memorial Sloan Kettering Cancer Center. “REFLECT is the first-ever positive Phase 3 trial against an active comparator in unresectable HCC. The efficacy and safety data from REFLECT are important findings for oncologists and others in the multidisciplinary teams who treat liver cancer, as well as for our patients who are affected by it.”

Adverse reactions, some of which can be serious or fatal, may occur with Lenvima, including hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, and wound healing complications. Based on the severity of the adverse reaction, Lenvima should be monitored, withheld or discontinued. Based on its mechanism of action and data from animal reproduction studies, Lenvima can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should be advised to use effective contraception. For more information, see “Important Safety Information” below.

REFLECT showed that Lenvima achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with Lenvima experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (HR: 0.92; 95% CI: 0.79–1.06). The OS analysis was conducted when 351 events had occurred in the Lenvima arm and 350 events had occurred in the sorafenib arm, as prespecified in the statistical analysis plan. In addition, Lenvima showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of PFS and ORR, as confirmed by a blinded independent imaging review (IIR):

  • Median PFS was doubled with Lenvima compared to sorafenib: 7.3 months versus 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.001) per blinded independent imaging review based on mRECIST criteria, and 7.3 months with Lenvima versus 3.6 months with sorafenib (HR: 0.65; 95% CI: 0.56–0.77) per RECIST 1.1.
  • Lenvima showed nearly 3.5 times the ORR of sorafenib: 41% (95% CI: 36-45%) vs. 12% (95% CI: 10-16%) per blinded independent imaging review based on mRECIST criteria, respectively (p<0.001), and 19% (95% CI: 15-22%) with Lenvima versus 7% (95% CI: 4-9%) with sorafenib per RECIST 1.1.
    • Per mRECIST: Treatment with Lenvima resulted in complete response (CR) = 2.1% (n=10) vs. 0.8% (n=4) with sorafenib; treatment with Lenvima resulted in partial response (PR) = 38.5% (n=184) vs. 11.6% (n=55) with sorafenib
    • Per RECIST 1.1: Treatment with Lenvima resulted in CR = 0.4% (n=2) vs. 0.2% (n=1) with sorafenib; treatment with Lenvima resulted in PR = 18.4% (n=88) vs. 6.3% (n=30) with sorafenib

In addition, median time to progression (TTP) was doubled with Lenvima compared to sorafenib: 7.4 months versus 3.7 months (HR: 0.60; 95% CI: 0.51–0.71; p<0.0001) per blinded independent imaging review based on mRECIST criteria, and 7.4 months with Lenvima versus 3.7 months with sorafenib (HR: 0.61; 95% CI: 0.51–0.72; p<0.0001) per RECIST 1.1. Time to progression is defined as time from randomization to radiological progression. Deaths during follow-up without evidence of radiological progression are censored. This differs from PFS and is less correlative to overall survival.

In REFLECT, the most common adverse reactions (≥20%) observed in patients treated with Lenvima were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism and nausea. The most common serious adverse reactions (≥2%) reported in patients treated with Lenvima were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%) and decreased appetite (2%).

The most common adverse reactions (≥20%) observed in patients who received sorafenib were palmar-plantar erythrodysesthesia syndrome, diarrhea, fatigue, hypertension, abdominal pain, decreased appetite, rash, decreased weight and arthralgia/myalgia. The most common serious adverse reactions (≥2%) reported in patients who received sorafenib were ascites (2%) and abdominal pain (2%).

It is also important to note that the dose for Lenvima for patients with unresectable HCC is based on the patient’s weight (12 mg for patients weighing 60 kilograms or more, 8 mg for patients weighing less than 60 kilograms); the recommended dosage and dose adjustments are described in the full prescribing information.

“Eisai strives to be a leading global R&D-based pharmaceutical company, driven by our human health care (hhc) mission to improve the lives of patients and their loved ones,” said Shaji Procida, President and Chief Operating Officer, Eisai Inc., and Commercial Head of the Oncology Business Group, Americas at Eisai. “That purpose is what has propelled us toward this win for patients with unresectable hepatocellular carcinoma. Our goal is to bring monumental solutions to patients and health care providers, changing expectations for the oncology landscape, and we look forward to continuing this work in our ongoing collaboration with Merck.”

“We are pleased by the FDA approval of Lenvima as it marks an important advancement in the treatment of unresectable hepatocellular carcinoma,” said Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories. “With our shared mission to find solutions for difficult-to-treat cancers, we look forward to working with Eisai to help bring this needed option to patients and physicians.”

Lenvima, a kinase inhibitor, was first approved in the U.S. in February 2015 for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC). In May 2016, Lenvima was approved in the U.S. in combination with everolimus, for patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy. Under the collaboration, Eisai and Merck initiated co-commercialization activities for Lenvima in the U.S. in June 2018. Since the initial launch, more than 10,000 patients were treated with Lenvima, which is approved in more than 50 countries worldwide.

About the REFLECT Trial (Study 304)

REFLECT was a large (N=954) phase 3, randomized, multicenter, open-label trial conducted by Eisai to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in patients with unresectable hepatocellular carcinoma (HCC). Patients at 154 trial sites in 20 countries were randomized to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival, tested first for non-inferiority to sorafenib, then for superiority. Patients randomized to the Lenvima arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. The key secondary efficacy endpoints of this study included progression-free survival, time to progression and objective response rate, tested for superiority to sorafenib. The results of the REFLECT trial were published online in The Lancet (Vol 391(10126):1163-1173) on February 9, 2018.

About Unresectable Hepatocellular Carcinoma (HCC)

The prevalence and mortality rate of hepatocellular carcinoma have been rising steadily over the past decade. Hepatocellular carcinoma is the most common type of liver cancer, accounting for about 90% of cases of primary liver cancer. The stage of disease at diagnosis largely determines treatment approach, with potentially curative options, like resection or transplantation, only available for early stage HCC. Unresectable HCC, a type of liver cancer that cannot be removed by surgery, has a worse prognosis, with a median survival of less than one year. Unfortunately, approximately 70% of patients are diagnosed too late to be eligible for resection or transplantation, and there have been limited treatment options available for patients with unresectable disease.

About Lenvima (lenvatinib) capsules 10 mg and 4 mg

Lenvima® (lenvatinib) is a kinase inhibitor that is indicated for the treatment of:

  • For the treatment of patients with locally recurrent or metastatic, progressive radioactive iodine-refractory differentiated thyroid cancer (DTC)
  • In combination with everolimus, for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
  • For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)

Lenvima, discovered and developed by Eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvima inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2α (FRS2α) phosphorylation.

About the Eisai and Merck Strategic Collaboration

In March 2018, Eisai and Merck, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of Lenvima® (lenvatinib). Under the agreement, the companies will jointly develop and commercialize Lenvima, both as monotherapy and in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab). In addition to ongoing clinical studies of the combination, the companies will jointly initiate new clinical studies evaluating the Lenvima/KEYTRUDA combination to support 11 potential indications in six types of cancer, as well as a basket trial targeting six additional cancer types. The Lenvima/KEYTRUDA combination is not approved in any cancer types today.

About Eisai Inc.

At Eisai Inc., human health care (hhc) is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.

Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, manufacturing and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at eisai.com/us and follow us on Twitter and LinkedIn.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2017 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Source: Merck

Posted: August 2018

Related Articles:

Lenvima (lenvatinib) FDA Approval History

Tagged with:

About author

Related Articles