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Data for KEYTRUDA® (pembrolizumab) in a Range of Gastrointestinal Cancers to be Presented at 2016 Gastrointestinal Cancers Symposium

On January 19, 2016 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that new and updated findings investigating the use of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, in multiple gastrointestinal cancers will be presented at this year’s Gastrointestinal (GI) Cancers Symposium in San Francisco, Jan. 21 – 23 (Press release, Merck & Co, JAN 19, 2016, View Source [SID:1234508810]). Updates on pembrolizumab include data on advanced esophageal carcinoma and new preliminary Phase 2 safety data in gastric cancer.

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"Advanced gastrointestinal cancers are difficult to treat and new therapies are needed," said Roger Dansey, M.D., senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "Through our rapidly advancing clinical program, we have seen promising results with KEYTRUDA in several gastrointestinal cancers, and are hopeful about the potential of KEYTRUDA for these patients."

The KEYTRUDA clinical trials program currently includes more than 30 tumor types in more than 200 clinical trials, including more than 80 trials that combine KEYTRUDA with other cancer treatments. More than 20 of these trials are evaluating KEYTRUDA in gastrointestinal cancers, including seven registration-enabling studies in gastric cancer, colorectal cancer and esophageal cancer. Registration-enabling trials of KEYTRUDA are also currently enrolling patients with melanoma, non-small cell lung cancer, head and neck cancer, bladder cancer, Hodgkin lymphoma, multiple myeloma, and breast cancer, and further trials are being planned for other malignancies.

Merck’s Immuno-Oncology Data at the 2016 GI Cancers Symposium

A full listing of KEYTRUDA abstracts for both oral and poster sessions is below:

Oral Presentations

(Abstract #7) Updated results for the advanced esophageal carcinoma cohort of the phase 1b KEYNOTE-028 study of pembrolizumab (MK-3475). T. Doi. Poster Presentation: Thursday, Jan. 21, 12:30 – 2:00 p.m. and 5:30 – 7:00 p.m. PST. Oral Presentation: Thursday, Jan. 21, 2:00 – 3:30 p.m. PST. Location: Moscone West Building.
(Abstract #195) PD-1 blockade in mismatch repair deficient non-colorectal gastrointestinal cancers. D. Le. Poster Presentation: Friday, Jan. 22, 12:30 – 2:00 p.m. and 5:30 – 7:00 p.m. PST. Oral Presentation: Friday, Jan. 22, 2:00 – 3:30 p.m. PST. Location: Moscone West Building.

Poster Presentations

(Abstract #TPS161) Pembrolizumab (MK-3475) plus 5-fluorouracil (5-FU) and cisplatin for first-line treatment of advanced gastric cancer: Preliminary safety data from KEYNOTE-059. C. Fuchs. Thursday, Jan. 21, 12:30 – 2:00 p.m. and 5:30 – 7:00 p.m. PST. Location: Moscone West Building.

(Abstract #TPS183) Pembrolizumab (MK-3475) versus paclitaxel as second-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Phase 3 KEYNOTE-061 study. A. Ohtsu. Thursday, Jan. 21, 12:30 – 2:00 p.m. and 5:30 – 7:00 p.m. PST. Location: Moscone West Building.

(Abstract #TPS184) Pembrolizumab (MK-3475) for recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma: Multicohort phase II KEYNOTE-059 study. C. Fuchs. Thursday, Jan. 21, 12:30 – 2:00 p.m. and 5:30 – 7:00 p.m. PST. Location: Moscone West Building.

(Abstract #TPS185) KEYNOTE-062: Phase III study of pembrolizumab (MK-3475) alone or in combination with chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. J. Tabernero. Thursday, Jan. 21, 12:30 – 2:00 p.m. and 5:30 – 7:00 p.m. PST. Location: Moscone West Building.

(Abstract #TPS189) Pembrolizumab (MK-3475) for previously treated metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: Phase II KEYNOTE-180 study. M. Shah. Thursday, Jan. 21, 12:30 – 2:00 p.m. and 5:30 – 7:00 p.m. PST. Location: Moscone West Building.

(Abstract #465) Phase 1/2a study of double immune suppression blockade by combining a CSF1R inhibitor (pexidartinib/PLX3397) with an anti PD-1 antibody (pembrolizumab) to treat advanced melanoma and other solid tumors. Z. Wainberg. Friday, Jan. 22, 12:30 – 2:00 p.m. and 5:30 – 7:00 p.m. PST. Location: Moscone West Building.

(Abstract #TPS787) KEYNOTE-164: Phase II study of pembrolizumab (MK-3475) for patients with previously treated, microsatellite instability-high advanced colorectal carcinoma. D. Le. Saturday, Jan. 23, 7:00 – 7:55 a.m. and 12:30 – 2:00 p.m. PST. Location: Moscone West Building.

(Abstract #TPS789) KEYNOTE-177: First-line, open-label, randomized, phase 3 study of pembrolizumab (MK-3475) versus investigator-choice chemotherapy for mismatch repair deficient or microsatellite instability-high metastatic colorectal carcinoma. L Diaz. Saturday, Jan. 23, 7:00 – 7:55 a.m. and 12:30 – 2:00 p.m. PST. Location: Moscone West Building.
About Gastrointestinal Cancer

Gastrointestinal cancer is a term for a group of cancers that affect the digestive system, including cancers of the esophagus, gallbladder, liver, pancreas, stomach, small intestine, colon, rectum, and anus. Cancer of the colon or rectum, also called colorectal cancer, is the third most common cancer in men and the second most common cancer in women worldwide, accounting for more than 600,000 cases each year. Esophageal cancer, a type of cancer that begins in the inner layer of the esophagus, is the eighth most common cancer worldwide with an estimated 456,000 new cases diagnosed in 2012.

About KEYTRUDA (pembrolizumab) Injection 100 mg

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is indicated in the United States for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is also indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. The NSCLC indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every three weeks for the approved indications.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Immune-mediated pneumonitis, including fatal cases, occurred in patients receiving KEYTRUDA. Pneumonitis occurred in 32 (2%) of 1,567 patients with melanoma, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%) pneumonitis. Pneumonitis occurred in 19 (3.5%) of 550 patients with non-small cell lung cancer (NSCLC), including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-mediated colitis occurred in 31 (2%) of 1,567 patients with melanoma, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis. Immune-mediated colitis occurred in 4 (0.7%) of 550 patients with NSCLC, including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in 16 (1%) of 1,567 patients with melanoma, including Grade 2 (0.1%), 3 (0.7%), and 4 (0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 13 (0.8%) of 1,567 patients with melanoma, including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis. Hypophysitis occurred in 1 (0.2%) of 550 patients with NSCLC, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

Hyperthyroidism occurred in 51 (3.3%) of 1,567 patients with melanoma, including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 127 (8.1%) of 1,567 patients with melanoma, including Grade 3 (0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550 patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA (pembrolizumab) for Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3 (0.1%) of 2,117 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.

Immune-mediated nephritis occurred in 7 (0.4%) of 1,567 patients with melanoma, including Grade 2 (0.2%), 3 (0.2%) and Grade 4 (0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the immune-mediated adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant, immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 1567 patients with melanoma: arthritis (1.6%), exfoliative dermatitis, bullous pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients with NSCLC: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.

Severe and life-threatening infusion-related reactions have been reported in 3 (0.1%) of 2,117 patients. Monitor patients for signs and symptoms of infusion related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA (pembrolizumab).

In Trial 6, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions were fatigue (28% with KEYTRUDA vs. 28% with ipilimumab), diarrhea (26% with KEYTRUDA), rash (24% with KEYTRUDA vs. 23% with ipilimumab), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

In Trial 2, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculo-papular rash (1%). The most common adverse reactions were fatigue (43% with KEYTRUDA), pruritus (28% with KEYTRUDA vs. 8% with chemotherapy), rash (24% with KEYTRUDA vs. 8% with chemotherapy), constipation (22% with KEYTRUDA vs. 20% with chemotherapy), nausea (22% with KEYTRUDA), diarrhea (20% with KEYTRUDA vs. 20% with chemotherapy), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients with NSCLC. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in 2% or more of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), decreased appetite (25%), cough (29%), and dyspnea (23%).

No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA.

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Genmab Announces U.S. FDA Approval of Arzerra® (ofatumumab) as Extended Treatment for Recurrent or Progressive CLL

On January 19, 2016 Genmab reports that the U.S. Food and Drug Administration (FDA) has approved a supplemental Biologics License Application (sBLA) for the use of Arzerra (ofatumumab) for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive chronic lymphocytic leukemia (CLL) (Press release, Genmab, JAN 19, 2016, View Source [SID:1234508814]). The application was submitted by Novartis under the ofatumumab collaboration between the two companies.

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This FDA approval is based on data from an interim analysis from a Phase III study, PROLONG (OMB112517) which evaluated ofatumumab maintenance therapy versus no further treatment in patients with a complete or partial response after second or third line treatment for CLL.

"The approval of Arzerra in the U.S. as extended treatment provides patients with relapsed CLL with a new treatment option that can help delay disease progression," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

A total of 474 patients were included in the analysis. Patients who received ofatumumab maintenance treatment lived 14.2 months longer without their disease worsening than patients who received no further treatment. Median progression free survival (PFS) as assessed by the investigators was 29.4 months for the ofatumumab treatment arm and 15.2 months for the observation arm (Hazard Ratio 0.50; p<0.0001).1

There were no unexpected safety findings. The most common adverse reactions (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection. The two most common grade 3-4 adverse events were neutropenia (22% in ofatumumab arm vs 8% in observation arm), and pneumonia (5% in ofatumumab arm vs 3% in observation arm). During the period between the first dose and 60 days after last dose there were two patients (1%) in the ofatumumab group who died due to adverse events and five patients (2%) in the observation group.1

6-K – Report of foreign issuer [Rules 13a-16 and 15d-16]

On January 19, 2016 Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC, NASDAQ:ONCY) reported that the first patients have been treated in a Phase 1b study of pembrolizumab (KEYTRUDA) in combination with REOLYSIN (pelareorep) and chemotherapy in patients with advanced pancreatic adenocarcinoma (REO 024) (Filing, 6-K, Oncolytics Biotech, JAN 19, 2016, View Source [SID:1234508813]).

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"Checkpoint inhibitors are an emerging class of therapeutic that allows the immune system to better recognize and target tumors, and the goal of this study is to assess their potential in combination with REOLYSIN," said Dr, Brad Thompson, President and CEO of Oncolytics. "Based on our early research it is possible that checkpoint inhibitors could support improved survival outcomes for patients treated with oncolytic viral therapy."

The study is enrolling patients 18 years or older with histologically confirmed advanced or metastatic pancreatic adenocarcinoma who have failed, or did not tolerate, first line treatment. It is an open-label Phase Ib trial designed to determine the safety and dose-limiting toxicities of REOLYSIN and chemotherapy (gemcitabine or irinotecan or fluorouracil, at the treating physician’s preference) in combination with pembrolizumab. Secondary endpoints include overall response rate and progression free survival by immune-related response criteria; overall survival; and effects of REOLYSIN and pembrolizumab when administered in combination as determined by analysis of pre- and post-treatment treatment biopsies and blood-based immune markers. Following an initial six to nine patient safety run-in, up to an additional 15 patients may be enrolled for further evaluation of safety and efficacy.

About Pancreatic Cancer
The American Cancer Society estimates that 53,070 Americans will be diagnosed with pancreatic cancer and an estimated 41,780 Americans will die from the disease in 2016. The prognosis for patients diagnosed with pancreatic cancer, regardless of stage, is generally poor; the relative five-year survival rate for all stages combined is approximately seven percent.

Delcath Announces Special Protocol Assessment Agreement With FDA For New Phase 3 Trial In Hepatic Dominant Ocular Melanoma

On January 19, 2016 Delcath Systems, Inc. (NASDAQ: DCTH), a specialty pharmaceutical and medical device company focused on oncology with an emphasis on the treatment of primary and metastatic liver cancers, reported that the Company has reached a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA) for the design of Delcath’s new Phase 3 clinical trial of Melphalan Hydrochloride for Injection for use with the Delcath Hepatic Delivery System (Melphalan/HDS) to treat patients with hepatic dominant ocular melanoma (Press release, Delcath Systems, JAN 19, 2016, View Source [SID:1234508808]).

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The SPA provides agreement that the Phase 3 trial design adequately addresses objectives that, if met, would support the submission for regulatory approval of Melphalan/HDS.

The agreement also represents the satisfactory resolution of a substantial number of the FDA’s issues in the Complete Response Letter (CRL) issued in September 2013. These issues were related to safety of a previous generation of the Melphalan/HDS device and procedure. Delcath completed the work necessary to satisfy these requirements prior to submitting its request for the SPA agreement.

The new pivotal trial, the FOCUS Clinical Trial for Patients with Hepatic Dominant Ocular Melanoma (the FOCUS trial), will evaluate the safety and efficacy profile of the Melphalan/HDS versus best alternative care. The primary endpoint will be overall survival, and secondary endpoints will include progression-free survival, overall response rate and quality-of-life measures. Full details of the Phase 3 clinical trial will be made public upon the launch of the study and will be available at www.clinicaltrials.gov.

"This agreement marks a major milestone for Delcath," said Jennifer K. Simpson, Ph.D., MSN, CRNP, President and Chief Executive Officer of Delcath. "Under this SPA our new FOCUS trial, if successful, will provide a clear pathway to an indication in hepatic dominant ocular melanoma for Melphalan/HDS. Additionally, through the dedicated work of our team and in close collaboration with the FDA, we have satisfied a substantial number of the requirements of the FDA’s 2013 CRL. Based on our commercial experience in Europe, the continued support and enthusiasm from Key Opinion Leaders and the clinical data that have been presented and published recently, we have confidence that our FOCUS trial can demonstrate the efficacy and safety necessary for a positive benefit/risk profile for Melphalan/HDS, and that the study’s objectives can be met. There is strong interest from leading cancer centers in the U.S. and Europe to participate in this study and we look forward to beginning enrollment in this registrational trial."

About Special Protocol Assessments
The Special Protocol Assessment (SPA) process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a new drug application. Final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in the Phase 3 clinical program. The SPA agreement may only be changed through a written agreement between the sponsor and the FDA, or if the FDA becomes aware of a substantial scientific issue essential to product efficacy or safety.

Baxalta Granted EU Marketing Authorization for ONCASPAR (pegaspargase) as a Component of Combination Therapy in Acute Lymphoblastic Leukaemia (ALL)

On January 19, 2016 Baxalta Incorporated (NYSE:BXLT), a global biopharmaceutical leader dedicated to delivering transformative therapies to patients with orphan diseases and underserved conditions, reported that the European Commission has granted Marketing Authorization for use of ONCASPAR as a combination therapy in acute lymphoblastic leukaemia (ALL) in paediatric patients from birth to 18 years, and adult patients (Press release, Baxalta, JAN 19, 2016, View Source [SID:1234508806]).

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With this approval, Baxalta is authorized to market ONCASPAR in the 28 member countries of the European Union (EU), as well as Iceland, Liechtenstein and Norway. The drug is already licensed to market in Argentina, Belarus, Germany, Kazakhstan, Poland, Russia, Ukraine and the United States.

"ONCASPAR has been used as an integral component of the treatment regimen for paediatric and adult patients with ALL for many years, in Europe, and worldwide," said Prof. Dr. med. Martin Schrappe, director of the department of general paediatrics at the Schleswig-Holstein University Hospital in Kiel, Germany. "Today’s marketing authorization will ensure that more patients across the EU will benefit from access to ONCASPAR as part of a standard of care regimen."

With this authorization, ONCASPAR will provide an important treatment option for more European patients with this rapidly progressing cancer of the white blood cells responsible for up to 80 percent of childhood leukaemia cases – the most common type of childhood cancer. However, ALL is not only a childhood cancer but can also occur in adults. Adult ALL accounts for approximately 40 percent of the annual incidence.2

"For more than two decades, ONCASPAR has fulfilled a clear need for an effective and well-tolerated treatment for ALL patients worldwide. This European marketing authorization allows Baxalta to expand the use of ONCASPAR, improving treatment outcomes for all patients in the EU," said David Meek, executive vice president and president, Oncology, Baxalta. "This approval is important as we strive to make a difference in the lives of people living with cancer in all parts of the world."

About ONCASPAR (pegaspargase) in the EU

ONCASPAR is indicated as a component of antineoplastic combination therapy in acute lymphoblastic leukaemia (ALL) in paediatric patients from birth to 18 years, and adult patients.3

Contraindications3

Hypersensitivity to the active substance or to any of the excipients
Severe hepatic impairment (bilirubin > 3 times upper limit of normal [ULN]; transaminases > 10 times ULN)
History of serious thrombosis with prior L-asparaginase therapy
History of pancreatitis, including the related to previous asparaginase therapy
History of serious hemorrhagic events with prior L-asparaginase therapy
EU Important Safety Information

ONCASPAR is indicated as a component of antineoplastic combination therapy in acute lymphoblastic leukaemia (ALL) in paediatric patients from birth to 18 years, and adult patients.

ONCASPAR is contraindicated in patients with severe hepatic impairment (defined as bilirubin > 3 times upper limit of normal [ULN]; transaminases > 10 times ULN), a history of serious thrombosis with prior L asparaginase therapy, a history of pancreatitis, including the related to previous asparaginase therapy and those with a history of serious hemorrhagic events with prior L asparaginase therapy.

Anaphylaxis or serious allergic reactions can occur; therefore, patients should be observed for one hour after administration. Discontinue ONCASPAR in patients with serious allergic reactions. Patients with abdominal pain should be evaluated for evidence of pancreatitis. Discontinue ONCASPAR in patients with pancreatitis. ONCASPAR should also be discontinued in patients with serious thrombotic events.

Glucose intolerance, in some cases irreversible, can occur; serum glucose should be monitored. Coagulopathy and hepatotoxicity can occur; appropriate monitoring should be performed.

The most common adverse reactions with ONCASPAR (=2%) are allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system (CNS) toxicity, thrombosis, coagulopathy, hyperbilirubinemia and elevated transaminases.

Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) has been reported in patients exposed to ONCASPAR.

Oncaspar may possess immunosuppressive activity. It is therefore possible that use of this medicinal product promotes infections in patients.

Combination therapy with Oncaspar can result in severe hepatic toxicity and central nervous system toxicity. Caution is required when Oncaspar is given in combination with other hepatotoxic substances, especially if there is preexisting hepatic impairment. In this case, patients should be monitored for liver impairment.

In the presence of symptoms of hyperammonemia (e.g. nausea, vomiting, lethargy, irritation), ammonia levels should be monitored closely.

Labeling may differ by country registration. Please refer to your country specific labeling for detailed information.

About Acute Lymphoblastic Leukaemia1

Acute lymphoblastic leukaemia (ALL) is a rare, fast-growing cancer of the white blood cells, and each year there are approximately 4,000-5,000 new cases in Europe and the United States, respectively. The disease is the most common childhood cancer and is responsible for more than 80 percent of childhood leukaemia cases. The five-year paediatric survival rate has climbed to more than 80 percent with modern therapies.