Morphotek Announces FDA Acceptance Of Investigational New Drug Application For Next-Generation Farletuzumab Antibody-Drug Conjugate MORAb-202

EXTON, Pa., Jan. 10, 2018 /PRNewswire/ -- Morphotek^®, Inc., a subsidiary of Eisai Inc., announced today that the U.S. Food and Drug Administration (FDA) accepted an Investigational New Drug (IND) Application for MORAb-202, an antibody-drug conjugate (ADC), to treat solid tumors that express folate receptor alpha (FRA).  A Phase 1 dose-escalation study will be conducted in the U.S. to evaluate the safety and preliminary efficacy of MORAb-202 in patients with solid tumors that express FRA.  The solid tumors to be studied include advanced or metastatic endometrial, non-small cell lung, ovarian and triple-negative breast cancer.

MORAb-202 is a novel investigational ADC that uses a cathepsin-cleavable linker to combine investigational farletuzumab with the microtubule inhibitor payload, eribulin.  Farletuzumab is a humanized antibody targeting FRA and has been studied in clinical trials in patients with FRA-expressing tumors.  FRA expression is observed in a large number of cancers, including endometrial, gastric, non-small cell lung, ovarian and triple-negative breast, but is largely absent from normal tissue.  Eribulin mesylate (Halaven^®) is approved in the U.S. for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for metastatic disease, including an anthracycline and a taxane in either the adjuvant or metastatic setting.

"We are pleased that the FDA has accepted our IND application to study MORAb-202, an antibody-drug conjugate that combines farletuzumab with the regulatory-approved eribulin, in solid tumors that express folate receptor alpha," said Nicholas Nicolaides, President and CEO of Morphotek. "This investigational agent has shown robust antitumor effects in a number of preclinical FRA-expressing tumor models, making it a potential promising candidate for the treatment of cancers that express this biomarker."

About Morphotek

Morphotek^®, Inc., a subsidiary of Eisai Inc., is a clinical-stage biotechnology company focused on developing novel classes of biological-based products to treat cancer, inflammatory and infectious diseases.  Our mission is to develop novel targeted therapies that attack underlying disease pathways, and in oncology indications, that can overcome the immunosuppressive effects by tumors on immune-mediated experimental therapies.  Our diverse pipeline includes clinical-stage biological products to lead targets folate receptor alpha, mesothelin and endosialin, as well as antibody-drug conjugates and bispecific antibodies to undisclosed targets in preclinical development.  Our mission is supported by proprietary cutting-edge technologies in antibody engineering, manufacturing and screening optimization platforms, along with our expertise in developing diagnostics to support patient selection and therapeutic strategy.  For more information, please visit www.morphotek.com.

About Eisai Inc.

At Eisai Inc., human health care (hhc) is our goal. We give our first thought 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, 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 www.eisai.com/US and follow us on Twitter and LinkedIn.

About Halaven^® (eribulin mesylate) Injection 
Halaven^® (eribulin mesylate) is a microtubule dynamics inhibitor indicated for the treatment of patients with:

• Metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease.  Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
• Unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.

Discovered and developed by Eisai, eribulin is a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai.  First in the halichondrin class, Halaven is a microtubule dynamics inhibitor.  Eribulin is believed to work primarily via a tubulin-based mechanism that causes prolonged and irreversible mitotic blockage, ultimately leading to apoptotic cell death.  Additionally, in preclinical studies of human breast cancer, eribulin demonstrated complex effects on the tumor biology of surviving cancer cells, including increases in vascular perfusion resulting in reduced tumor hypoxia, and changes in the expression of genes in tumor specimens associated with a change in phenotype, promoting the epithelial phenotype, opposing the mesenchymal phenotype.  Eribulin has also been shown to decrease the migration and invasiveness of human breast cancer cells.

Important Safety Information for Halaven (eribulin mesylate) Injection

Warnings and Precautions

Neutropenia: Severe neutropenia (ANC <500/mm³) lasting >1 week occurred in 12% of patients with mBC and liposarcoma or leiomyosarcoma.  Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications.  Febrile neutropenia occurred in 0.9% of patients with liposarcoma or leiomyosarcoma, and fatal neutropenic sepsis occurred in 0.9% of patients.  Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels.  Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias.  Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting >7 days.

Peripheral Neuropathy: Grade 3 peripheral neuropathy occurred in 8% of patients with mBC (Grade 4=0.4%) and 22% developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days).  Neuropathy lasting >1 year occurred in 5% of patients with mBC.  Grade 3 peripheral neuropathy occurred in 3.1% of patients with liposarcoma and leiomyosarcoma receiving HALAVEN and neuropathy lasting more than 60 days occurred in 58% (38/65) of patients who had neuropathy at the last treatment visit.  Patients should be monitored for signs of peripheral motor and sensory neuropathy.  Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose.  Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose.

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities.  Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy.  Avoid in patients with congenital long QT syndrome.

Adverse Reactions 
In patients with mBC receiving HALAVEN (eribulin mesylate) Injection, the most common adverse reactions (≥25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%).  Febrile neutropenia (4%) and neutropenia (2%) were the most common serious adverse reactions.  The most common adverse reaction resulting in discontinuation was peripheral neuropathy (5%).

In patients with liposarcoma and leiomyosarcoma receiving HALAVEN, the most common adverse reactions (≥25%) reported in patients receiving HALAVEN were fatigue (62%), nausea (41%), alopecia (35%), constipation (32%), peripheral neuropathy (29%), abdominal pain (29%), and pyrexia (28%).  The most common (≥5%) Grade 3-4 laboratory abnormalities reported in patients receiving HALAVEN were neutropenia (32%), hypokalemia (5.4%), and hypocalcemia (5%).  Neutropenia (4.9%) and pyrexia (4.5%) were the most common serious adverse reactions.  The most common adverse reactions resulting in discontinuation were fatigue and thrombocytopenia (0.9% each).

Use in Specific Populations

Lactation: Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.

Hepatic and Renal Impairment: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe renal impairment.

For more information about HALAVEN, click here for the full Prescribing Information.

SOURCE Morphotek, Inc.

Related Links

http://www.morphotek.com