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8-K – Current report

On February 3, 2016 Advaxis, Inc. (NASDAQ: ADXS), a clinical stage biotechnology company developing cancer immunotherapies, reported that it has entered into a co-development and commercialization agreement with Especificos Stendhal SA de CV ("Stendhal"), for Advaxis’ lead Lm Technology immunotherapy, axalimogene filolisbac (ADXS-HPV), in HPV-associated cancers (Filing, 8-K, Advaxis, FEB 4, 2016, View Source [SID:1234508970]). Stendhal is a privately held Latin American specialty pharmaceutical company that partners with leading drug companies to deliver effective solutions for life-threatening diseases in Latin American markets.

Under the terms of the Agreement, Stendhal will pay $10 million toward the expenses of AIM2CERV, a planned global Phase 3 clinical trial in women with high-risk, locally advanced cervical cancer. This payment covers a significant portion of the total planned study costs. Stendhal will also work with Advaxis to complete the clinical trial of axalimogene filolisbac in Mexico, Brazil, Colombia, and other investigational sites in Latin American countries. Additionally, Stendhal will manage the regulatory approval process, promotion, commercialization and market access for axalimogene filolisbac in these markets. Advaxis and Stendhal will share profits on a pre-determined basis.

Stendhal has a long history of partnering with leading pharmaceutical companies to bring therapies for HIV, infectious disease, and neurologic and cardiovascular disease to its Latin American markets. This new partnership with Advaxis will expand its growing portfolio in oncology and is one of the first of its kind in Latin America to make cancer immunotherapies available in the region.

HPV-related cancer is a looming public health issue in Latin America. According to the World Health Organization, cervical cancer mortality rates are three times higher in Latin America and the Caribbean than in North America. More than 83,000 women are diagnosed annually and, without intervention, mortality is projected to increase to 45 percent by 2030. HPV is also prevalent in 90.4 percent of anal cancer in Latin America and the Caribbean.

"We’re pleased to announce our agreement with Stendhal, which enables us to greatly expand the clinical program for, and the potential impact of, axalimogene filolisbac in HPV-related cancers," said Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. "We now have the potential to address an important unmet medical need in an area of the world where the rate of HPV-associated cancers is unfortunately extremely high."

"Our mission is to bring new treatments to Latin America and ensure that patients have access to therapies that have the potential to save their lives. Women throughout our region are facing increasing rates of HPV and the burden of cervical cancer," said Carlos Arenas, Chief Executive Officer of Stendhal. "It is through partnerships such as this one that we can alter the course of disease and address the health inequalities many in Latin America face."

About Cervical Cancer

Cervical cancer is the fourth most common cancer in women worldwide. In the U.S., nearly 13,000 new cases are diagnosed annually and approximately 4,100 deaths are reported because of cervical cancer. According to the WHO/ICO Information Centre on HPV and Cervical Cancer, about 3.9 percent of women in the U.S. are estimated to harbor high-risk cervical HPV infection at a given time, and 71.7 percent of invasive cervical cancers are attributed to high-risk HPV strains.

About Anal Cancer

Anal cancer is a fairly rare form of cancer in the United States, but the number of new anal cancer cases has been rising for years. The risk of being diagnosed with anal cancer in one’s lifetime is about 1 in 500. According to the American Cancer Society, approximately 7,270 new cases of anal cancer were diagnosed and about 1,010 people died of the disease in 2014.

HPV-Associated Head and Neck Cancers

More than 90 percent of head and neck squamous cell oropharyngeal cancers originate from the mucosal linings of the oral cavity, pharynx, or larynx. Currently, 60 to 80 percent of these cancers are caused by HPV. Head and neck cancers are treated by surgical removal of the cancer and lymph nodes, often followed by radiation and chemotherapy based on the extent of the disease. While patients may achieve good long-term survival, standard treatments can change their physical appearance and are associated with significant short and long-term toxicities which may interfere with salivary gland function, taste, smell, and the ability to swallow.

The incidence of HPV-associated head and neck cancers has been increasing at an epidemic rate, while head and neck cancers from other causes have been decreasing. According to the WHO, approximately 15 to 20 percent of the 400,000 new cases of head and neck cancer are HPV-related. In the US, there are about 12,000 new cases of HPV-associated head and neck cancer per year and it affects men about 3 times more frequently than women. HPV-associated head and neck cancer is growing fastest in developed countries like the U.S.

About Axalimogene Filolisbac

Axalimogene filolisbac (ADXS-HPV) is Advaxis’ lead Lm Technology immunotherapy candidate for the treatment of HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, axalimogene filolisbac showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology. Axalimogene filolisbac has Orphan Drug Designation in the U.S. for the treatment of anal cancer.

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RIBOXX PHARMACEUTICALS and TOLLYS S.A.S Announce an Exclusive License Agreement for Treatment of Toll-like 3 Positive Cancers

On February 4, 2016 RIBOXX PHARMACEUTICALS, a biotech company developing Toll-like-receptor (TLR) and RIG-I-like-Receptor (RLR) ligands, and TOLLYS SAS, a biotech company developing new therapeutic strategies in cancer, reported that they have signed a license agreement that grants TOLLYS exclusive global development and commercialization rights to a new drug development program, which RIBOXX will refer to as APOXXIM (Press release, Riboxx Pharmaceuticals, FEB 4, 2016, View Source [SID:1234508983]).

Under the terms of the license agreement, TOLLYS will assume sole responsibility for global development and commercialization of APOXXIM product candidate. Riboxx will be responsible for manufacturing and supply of APOXXIM to TOLLYS.

APOXXIM is a Toll-like Receptor 3 (TLR3)-ligand that eliminates cancer cells by activating the TLR3 pathway. APOXXIM displays unique physico-chemical and biological properties, as well as optimal biodisponibility with increased stability to degradation in body fluids such as human plasma. APOXXIM is manufactured with the unique patented cGMP TENPORA-Process of Riboxx.

Jacques Rohayem, CEO and CSO of RIBOXX PHARMACEUTICALS declared: "We are very thrilled to start this collaboration with TOLLYS, a company with a very strong scientific expertise in cancer therapy. This collaboration expands the portfolio of Riboxx drug development programs such as RIBOXXIM, RIBOXXOL and QUADROXXIM, mainly focusing on cancer immunotherapy."

Jacques-François Martin, President of TOLLYS declared: "TOLLYS is very pleased to start this collaboration towards the development of a new and unique therapeutic strategy in cancer. The potential of TLR3-Ligands such as APOXXIM to treat cancer has been extensively studied in the past decades by scientists at TOLLYS, with a particular focus on TLR3-positive cancers".

About RIBOXX PHARMACEUTICALS
RIBOXX PHARMACEUTICALS is a biotech company developing proprietary Toll-like-receptor (TLR) ligands and RIG-I-like-Receptor (RLR) ligands for applications in cancer immunotherapy. RIBOXX IP portfolio includes 17 PCT patent families so far, with 8 PCT patents granted in EU and/or Japan.

About TOLLYS SAS
TOLLYS SAS is a biotech company developing drugs targeting TLR3-positive cancer cells. TOLLYS SAS has a strong expertise in the design and development of anti-cancer strategies through activation of TLR3-pathway.

OncoGenex Announces Reduction in Force to Extend Cash Runway and Align Operations with Clinical Development Priorities

On February 4, 2016 OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) reported that it is implementing a plan to reduce operating expenses, including a workforce reduction of approximately 27% (Press release, OncoGenex Pharmaceuticals, FEB 4, 2016, View Source [SID:1234508980]). The Company expects cost savings associated with the reduction of employees and consultants, together with the elimination of certain planned expenditures not required for the completion of ongoing trials, will extend cash runway into the third quarter of 2017.

OncoGenex will remain focused on executing clinical development plans in order to reach several near-term milestones for both the custirsen and apatorsen programs.

As of December 31, 2015, the Company’s cash, cash equivalents and short-term investments were $55.2 million. Based on current expectations, the Company believes that resources will be sufficient to fund currently planned operations into the third quarter of 2017. Depending on timing of enrollment or event-driven final analyses, the expected timing of key milestones and activities are as follows:

Custirsen
Announcing AFFINITY trial results, the phase 3 trial evaluating a survival benefit for custirsen in combination with cabazitaxel as second-line chemotherapy in approximately 630 patients with castrate-resistant prostate cancer. The final analysis for the intent-to-treat population is expected in the third quarter of 2016.
Announcing ENSPIRIT trial results, the phase 3 trial evaluating a survival benefit for custirsen in combination with docetaxel as second-line chemotherapy in approximately 700 patients with non-small cell lung cancer. The final survival analysis is expected in the first half of 2017.
Apatorsen
Announcing Borealis-2 trial results, an investigator-sponsored, randomized phase 2 trial evaluating apatorsen in combination with docetaxel treatment compared to docetaxel treatment alone in patients with advanced or metastatic bladder cancer. Final results are expected in the second half of 2016.
Announcing Spruce trial results for the overall survival endpoint, the investigator-sponsored, randomized, placebo-controlled phase 2 trial evaluating apatorsen treatment with carboplatin and pemetrexed chemotherapy in patients with previously untreated advanced non-squamous NSCLC. Results are expected in the second half of 2016.
Preparing an investigational new drug application for FDA submission of apatorsen for intravesical administration in combination with Bacillus Calmette-Guerin (BCG) treatment in patients with non-muscle invasive bladder cancer.

Phase 3 Study of BLINCYTO® (Blinatumomab) Met Primary Endpoint Of Overall Survival In Patients With B-Cell Precursor Acute Lymphoblastic Leukemia

On February 4, 2016 Amgen (NASDAQ:AMGN) reported that the results of a prespecified interim analysis showed that the primary endpoint of improved overall survival was met in the Phase 3 TOWER study (Press release, Amgen, FEB 4, 2016, View Source [SID:1234508978]). The randomized, open-label TOWER study evaluated the efficacy of BLINCYTO (blinatumomab) versus standard of care (SOC) in adult patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The independent data monitoring committee recommended, and Amgen has accepted, that the study end early for efficacy.

The BLINCYTO adverse events observed in the TOWER study were consistent with the known safety profile of BLINCYTO. Secondary endpoints are currently being evaluated. These interim data will be submitted to a future medical conference and for publication.

"The FDA’s breakthrough therapy designation and accelerated approval of BLINCYTO underscore the dire prognosis for these patients. This is the first study to demonstrate an overall survival benefit for these patients with an immunotherapy, and this is a tremendously rare achievement in relapsed and refractory ALL," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We will work with regulatory authorities towards a full approval for BLINCYTO in this population."

About TOWER Study

The TOWER study was a Phase 3, randomized, open-label study investigating the efficacy of the BiTE antibody BLINCYTO versus SOC chemotherapy in adult subjects with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL. Patients were randomized in a 2:1 ratio to receive BLINCYTO or treatment with investigator choice of one of four protocol defined SOC chemotherapy regimens. The primary endpoint was OS. Click here to read about the trial on ClinicalTrials.gov.

About ALL

ALL is an aggressive cancer of the blood and bone marrow, the spongy tissue inside bones where blood cells are made. The disease progresses rapidly and affects immature blood cells. Patients with ALL have abnormal white blood cells (lymphocytes) that crowd out healthy white blood cells, red blood cells and platelets, leading to infection, anemia (fatigue), easy bleeding and other serious side effects.

About BLINCYTO (blinatumomab)

BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

BiTE antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration, and is now approved in the U.S. for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

About BiTE Technology

Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

BLINCYTO U.S. Product Safety Information

Important Safety Information Regarding BLINCYTO (blinatumomab) U.S. Indication

This safety information is specific to the current U.S. approved indication.

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications
BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS occurred in patients receiving BLINCYTO. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO as outlined in the Prescribing Information (PI).

Neurological Toxicities: Approximately 50% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 15% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The median time to onset of any neurological toxicity was 7 days. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.

Infections: Approximately 25% of patients receiving BLINCYTO experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.

Tumor Lysis Syndrome (TLS): Life-threatening or fatal TLS has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.

Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.

Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.

Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment. The majority of these events were observed in the setting of CRS. The median time to onset was 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.

Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and anti-leukemic chemotherapy. Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).

Adverse Reactions

The most commonly reported adverse reactions (≥ 20%) in clinical trials were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), diarrhea (20%) and constipation (20%).

Serious adverse reactions were reported in 65% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, pneumonia, sepsis, neutropenia, device-related infection, tremor, encephalopathy, infection, overdose, confusion, Staphylococcal bacteremia, and headache.

U.S. Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm. It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose). Please see full U.S. Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.

FDA Approves Merck’s Single-Dose EMEND® (fosaprepitant dimeglumine) for Injection, in Combination with Other Antiemetic Agents, for the Prevention of Delayed Nausea and Vomiting in Adults Receiving Moderately Emetogenic Chemotherapy (MEC)

On February 4, 2016 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for single-dose EMEND (fosaprepitant dimeglumine) for injection, Merck’s substance P/neurokinin-1 (NK1) receptor antagonist, in combination with other antiemetic medicines, for the prevention of delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC) (Press release, Merck & Co, FEB 4, 2016, View Source [SID:1234508976]). EMEND has not been studied for the treatment of established nausea and vomiting.

The FDA approval is supported by data from a Phase 3 study that showed single-dose EMEND for injection, combined with other anti-vomiting medicines, provided greater protection from delayed nausea and vomiting following administration of moderately emetogenic chemotherapy versus an active control regimen. With this approval, EMEND for injection is the first intravenous single-dose NK1 receptor antagonist approved in the U.S. for both highly emetogenic chemotherapy (HEC) as well as MEC.

EMEND for injection is contraindicated in patients who are hypersensitive to any component of the product and in patients taking pimozide.

"Despite significant advances in supportive care, nausea and vomiting has remained a challenge for many cancer patients undergoing moderately emetogenic chemotherapy – and has historically required multi-day antiemetic therapy," said Stuart Green, vice president, clinical research, Merck Research Laboratories. "Today’s approval of an expanded indication for EMEND for injection means that physicians now have a new single-dose intravenous option, combined with other anti-vomiting medicines, for the prevention of delayed nausea and vomiting in these patients."

Data Supporting the FDA Approval

The FDA approval of this new indication was based in part on findings from a randomized, parallel, double-blind, active comparator-controlled study that evaluated EMEND (fosaprepitant dimeglumine) for injection (150 mg) as a single intravenous infusion in combination with ondansetron and dexamethasone (referred to as the EMEND regimen) (n=502) compared with ondansetron and dexamethasone alone (control regimen) (n=498) in patients receiving MEC. The primary endpoint was complete response (defined as no vomiting and no use of rescue therapy) in the delayed phase (25 to 120 hours following initiation of chemotherapy) of chemotherapy-induced nausea and vomiting. A 78.9 percent complete response rate was observed with the EMEND regimen compared to 68.5 percent with the control regimen (p<0.001). The results of this trial were presented at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), and have now been published in the journal Annals of Oncology.

The most common adverse reactions reported in the EMEND regimen versus control regimen were fatigue (15% vs 13%), diarrhea (13% vs 11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain in extremity (2% vs 1%).

About EMEND (fosaprepitant dimeglumine) for Injection

EMEND for injection is an intravenous prodrug of the oral formulation of EMEND (aprepitant). When EMEND for injection is administered, fosaprepitant is rapidly converted in the body to aprepitant. EMEND (aprepitant) is a selective high-affinity antagonist of human substance P/neurokinin-1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV).

EMEND for injection, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin and for the prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).

EMEND has not been studied for the treatment of established nausea and vomiting.

Selected Important Safety Information for EMEND (fosaprepitant dimeglumine) for Injection

EMEND is contraindicated in patients who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions, flushing, erythema, and dyspnea have been reported. If symptoms occur, discontinue the infusion and administer appropriate medical therapy. Do not reinitiate the infusion in patients who experience these symptoms during first-time use.

EMEND is contraindicated in patients taking pimozide. Inhibition of CYP3A4 by aprepitant, the active drug, could result in elevated plasma concentrations of this drug, which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation.

Fosaprepitant, a prodrug of aprepitant, is a weak inhibitor of CYP3A4, and aprepitant is a substrate, inhibitor, and inducer of CYP3A4. Use of EMEND with other drugs that are CYP3A4 substrates, may result in increased plasma concentrations of the concomitant drug. Use of EMEND with strong or moderate CYP3A4 inhibitors (eg, ketoconazole, diltiazem) may increase plasma concentrations of aprepitant and result in an increased risk of adverse reactions related to EMEND. Use of EMEND with strong CYP3A4 inducers (eg, rifampin) may result in a reduction in aprepitant plasma concentrations and decreased efficacy of EMEND.

Reduce the dose of the co-administered corticosteroid on Days 1 and 2 for patients receiving HEC and on Day 1 for patients receiving MEC as follows: oral dexamethasone by approximately 50%; oral methylprednisolone by approximately 50%; and intravenous methylprednisolone by approximately 25%.

Monitor patients taking vinblastine, vincristine, or ifosfamide or other chemotherapeutic agents that are metabolized by CYP3A4 for chemotherapeutic-related adverse reactions. No dosage adjustments are needed when etoposide, vinorelbine, paclitaxel, or docetaxel are administered.

Coadministration of EMEND with warfarin (a CYP2C9 substrate) may result in a clinically significant decrease in international normalized ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, monitor the INR in the 2-week period, particularly at 7 to 10 days, following initiation of EMEND with each chemotherapy cycle.

The efficacy of hormonal contraceptives (including birth control pills, skin patches, implants, and certain IUDs) may be reduced during coadministration with and for 28 days after the last dose of EMEND. Advise patients to use effective alternative or backup methods of contraception during treatment with EMEND (fosaprepitant dimeglumine) and for 1 month following administration of EMEND.

In the MEC study, the most common adverse reactions reported in at least 2% of patients treated with the EMEND regimen and at a greater incidence than the control regimen were: fatigue (15% EMEND regimen vs 13% control regimen), diarrhea (13% vs 11%), neutropenia (8% vs 7%), asthenia (4% vs 3%), anemia (3% vs 2%), peripheral neuropathy (3% vs 2%), leukopenia (2% vs 1%), dyspepsia (2% vs 1%), urinary tract infection (2% vs 1%), and pain in extremity (2% vs 1%). In the HEC study, the safety profile was generally similar to that seen in the MEC study with fosaprepitant and prior HEC studies with aprepitant.

In the MEC study, infusion-site reactions were reported in 2.2% of patients treated with the EMEND regimen compared to 0.6% of patients treated with the control regimen, including infusion-site pain (1.2% EMEND regimen vs 0.4% control regimen), injection-site irritation (0.2% vs 0.0%), vessel puncture-site pain (0.2% vs 0.0%), and infusion-site thrombophlebitis (0.6% vs 0.0%). In the HEC study, which compared fosaprepitant to aprepitant, infusion-site reactions occurred at a higher incidence in the fosaprepitant group (3.0%) than in the aprepitant group (0.5%). The following additional infusion-site reactions occurred in the HEC study and were not reported in the MEC study: infusion-site erythema (0.5% for fosaprepitant vs 0.1% for aprepitant), infusion-site pruritus (0.3% vs 0.0%), and infusion-site induration (0.2% vs 0.1%).