On August 18, 2015 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported the U.S. Food and Drug Administration (FDA) has accepted for review a supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, Merck & Co, AUG 18, 2015, View Source [SID:1234507293]). Schedule your 30 min Free 1stOncology Demo! Merck is seeking approval for KEYTRUDA, at the currently approved dose of 2 mg/kg every three weeks, for the first-line treatment of unresectable or metastatic melanoma patients. The FDA granted Priority Review with a PDUFA, or target action, date of December 19, 2015. Additionally, the FDA has extended the action date for a separate sBLA for KEYTRUDA for the treatment of patients with ipilimumab-refractory advanced melanoma. The new action date is now December 24, 2015.
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"Through our clinical program for KEYTRUDA we have accumulated substantial data on the role of our anti-PD-1 therapy in advanced melanoma. We look forward to the FDA’s review of each of these applications, and to delivering on our goal of helping patients with advanced melanoma to achieve long-term disease control and survival," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories.
KEYTRUDA is currently indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This 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.
The sBLA submission for first-line use in advanced melanoma was based in part on data from KEYNOTE-006, a Phase 3 study which evaluated KEYTRUDA in 834 patients with unresectable or metastatic melanoma with progression of disease. Findings from this study were presented at the 2015 American Associated for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and published in the New England Journal of Medicinei.
Update on sBLA in Ipilimumab-Refractory Advanced Melanoma
The sBLA for ipilimumab-refractory advanced melanoma included data from KEYNOTE-002. KEYNOTE-002 is the Phase 2 study which demonstrated KEYTRUDA was superior to chemotherapy in helping more patients with ipilimumab-refractory advanced melanoma achieve progression-free survival (PFS). In an effort to provide the FDA with the most robust data for KEYTRUDA in this population, Merck submitted an additional analysis from KEYNOTE-002. The submission constitutes a major amendment which will require additional time for review.
About KEYTRUDA (pembrolizumab)
KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.
Merck is advancing a broad and fast-growing clinical development program for KEYTRUDA with more than 100 clinical trials – across more than 30 tumor types and enrolling more than 16,000 patients – both as a monotherapy and in combination with other therapies.
Selected Important Safety Information for KEYTRUDA
Pneumonitis occurred in 12 (2.9%) of 411 patients, including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively. 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 pneumonitis.
Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients respectively, receiving KEYTRUDA (pembrolizumab). 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.
Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients, including a Grade 4 case in 1 (0.2%) patient, receiving KEYTRUDA. 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 2 (0.5%) of 411 patients, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Monitor for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3; and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.
Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients respectively, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. 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 corticosteroids for Grade 3 or greater hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.
Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia and other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA in cases of severe hyperglycemia until metabolic control is achieved.
Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Other clinically important immune-mediated adverse reactions can occur. The following clinically significant, immune-mediated adverse reactions occurred in patients treated with KEYTRUDA (pembrolizumab): exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, severe dermatitis including bullous pemphigoid, myasthenic syndrome, optic neuritis, and rhabdomyolysis.
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 of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or less. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
Infusion-related reactions, including severe and life-threatening reactions, have occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe or life-threatening reactions, stop infusion and permanently discontinue KEYTRUDA.
Based on its mechanism of action, KEYTRUDA may 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.
For the treatment of advanced melanoma, KEYTRUDA was discontinued for adverse reactions in 9% of 411 patients across all doses studied. Adverse reactions, reported in at least two patients, that led to discontinuations of KEYTRUDA were: pneumonitis, renal failure, and pain. Serious adverse reactions occurred in 36% of patients receiving KEYTRUDA. The most frequent serious adverse drug reactions reported in 2% or more of patients were renal failure, dyspnea, pneumonia, and cellulitis.
The most common adverse reactions (reported in ≥20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).
The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA (pembrolizumab). 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. Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.
About Melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The incidence of melanoma has been increasing over the past four decades – approximately 232,000 new cases were diagnosed worldwide in 2012. In the U.S., melanoma is one of the most common types of cancer diagnosed and is responsible for the vast majority of skin cancer deaths. In 2015, an estimated 73,870 people are expected to be diagnosed and an estimated 9,940 people are expected to die of the disease in the U.S. alone. The five-year survival rates for advanced or metastatic melanoma (Stage IV) are estimated to be 15 to 20 percent.
Author: [email protected]
Deciphera Pharmaceuticals Announces Study Results for Altiratinib Demonstrating Inhibition of Three Major Cancer-Promoting Pathways to Durably Block Tumor Growth and Invasion
On August 18, 2015 Deciphera Pharmaceuticals, a clinical-stage biotechnology company focused on developing advanced kinase inhibitor treatments targeting the tumor cell and the tumor microenvironment, reported the publication of study results describing the preclinical profile of its Phase 1 anti-cancer product candidate, altiratinib, a balanced, spectrum-selective inhibitor of MET, TIE2, and VEGFR2 kinases (Press release, Deciphera Pharmaceuticals, AUG 18, 2015, View Source [SID:1234507291]). Schedule your 30 min Free 1stOncology Demo! The article, which will appear in the September 2015 issue of Molecular Cancer Therapeutics, was pre-published on-line on August 18, 2015. Altiratinib is currently in Phase 1 clinical evaluation in cancer patients (NCT02228811).
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In the article the authors describe how altiratinib’s balanced inhibition of the three key kinases, MET, TIE2, and VEGFR2 was achieved using Deciphera’s proprietary switch control kinase inhibitor platform. Moreover, altiratinib was shown to inhibit not only wild type MET, but also oncogenic mutant forms of MET not readily inhibited by other MET inhibitors in development. The ability to inhibit MET mutants during the course of treatment is a key component to altiratinib’s product profile, which Deciphera believes will provide more durable therapy for cancer patients compared to existing agents. MET mutations are driver mutations in certain cancers and can also arise as a resistance mechanism in patients with pre-existing MET amplifications, highlighting the need for durable inhibition of various forms of genomically altered MET.
The report further discloses altiratinib’s ability to block drug resistance mechanisms mediated by the tumor microenvironment. Through its balanced inhibitory potency, altiratinib was shown to inhibit three major evasive cancer (re)vascularization and resistance pathways with comparable single-digit nanomolar inhibitory potency, including HGF, ANG, and VEGF and to block tumor invasion and metastasis. Notably, in a glioblastoma tumor model known to exhibit these tumor microenvironment disease progression mechanisms, altiratinib was shown to double the overall survival of mice compared to vehicle control treated mice and, in combination with bevacizumab, to double survival compared to single-agent bevacizumab-treated mice.
"Altiratinib has a unique profile with the potential to provide cancer patients with a more durable therapy than currently approved and investigational kinase inhibitors in this space," said Daniel L. Flynn, Ph.D., Chief Scientific Officer and Founder of Deciphera Pharmaceuticals. "Already clinical oncologists are seeing the rise in secondary MET mutations, which confer resistance to current MET inhibitors. Altiratinib’s mechanism of action targets not only the wild type form of MET kinase, but also these various secondary mutations."
OncoSec Announces First Patient Enrolled in Phase II Clinical Trial Evaluating Combination of ImmunoPulse™ IL-12 and Anti-PD-1 Treatment
On August 18, 2015 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported enrollment of the first patient into the Phase II Investigator Sponsored Trial led by the University of California, San Francisco (UCSF) to assess the anti-tumor activity, safety, and tolerability of the combination of OncoSec’s investigational therapy, ImmunoPulse IL-12, and Merck’s approved anti-PD-1 agent, KEYTRUDA (pembrolizumab), in patients with unresectable metastatic melanoma (Press release, OncoSec Medical, AUG 18, 2015, View Source [SID:1234507287]). Schedule your 30 min Free 1stOncology Demo! The primary endpoint is the best Overall Response Rate (bORR) of the combination regimen in patients whose tumors are characterized by low numbers of tumor-infiltrating lymphocytes (TILs).
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"There is increasing evidence that tumors need to be inflamed and have TILs in order for anti-PD-1 therapies to be most effective," said Mai H. Le, MD, Chief Medical Officer of OncoSec. "Both preclinical and clinical evidence suggest that ImmunoPulse IL-12 can promote tumor immunogenicity. We anticipate that ImmunoPulse IL-12 will increase the proportion of patients who will respond to immune checkpoint inhibitors like KEYTRUDA and that the combination will have synergistic anti-tumor activity."
"This is the first study in the field of immuno-oncology to evaluate the combination of DNA-based interleukin-12 with electroporation and an anti-PD-1/PD-L1 inhibitor," said Punit Dhillon, CEO and President of OncoSec. "We believe the combination of OncoSec’s intratumoral cancer immunotherapy and checkpoint inhibitors has the potential to be a powerful approach in the fight against cancer."
This multi-center, open label, single-arm trial will enroll approximately 42 patients with unresectable, "low-TIL" metastatic melanoma. Alain Algazi, MD, a skin cancer specialist in the Melanoma Center at the UCSF Helen Diller Family Comprehensive Cancer Center, is the study’s sponsor and principal investigator. The key endpoints of the study include: best Overall Response Rate by RECIST v1.1 and immune related-Response Criteria (irRC); safety and tolerability; duration of response; 24-week landmark progression-free survival; median progression-free survival; and overall survival.
The treatment schedule for the trial follows the standard schedule for pembrolizumab. Pembrolizumab will be administered systematically once every three weeks and ImmunoPulse IL-12 will be administered on three separate days every six weeks. ImmunoPulse IL-12 employs intratumoral delivery of DNA-based IL-12 followed by electroporation. Merck will supply pembrolizumab, and OncoSec will provide ImmunoPulse IL-12.
To learn more about the trial, visit www.oncosec.com. Additional details can also be found at www.clinicaltrials.gov.
About Melanoma
Melanoma is one of the most dangerous forms of skin cancer and accounts for the vast majority of skin cancer deaths.1 When melanoma is caught early enough, surgical excision can be curative in the majority of Stage I and II melanomas. The overall 5-year survival rate for patients with localized melanoma is 98 percent in the United States.1 At later stages, malignant melanoma remains a deadly and frequently difficult to treat cancer. The overall 5-year survival rate for patients falls to 63 percent when the disease reaches the lymph nodes and 16 percent when the disease metastasizes to distant organs.1
Melanoma that has spread to distant sites may be treated with surgery, immunotherapy, chemotherapy and/or radiation therapy.1 Numerous chemotherapy regimens have been tested in melanoma with only modest success and limited overall survival benefit.2 Two approaches – checkpoint inhibitors and targeted kinase inhibitors – have demonstrated improvement in overall survival of patients compared to chemotherapy. 2
While immunotherapy can be extremely effective, the currently approved regimens do not benefit the majority of patients. However, early data of combination approaches with immunotherapies are promising.2 Researchers also continue to focus efforts on targeting pathways of T cell activation.3 The presence of CD8+ T cells seems to correlate with improved prognosis and long-term survival in solid malignancies, such as melanoma,4,5 thus many emerging experimental immunotherapies seek to enhance the tumor’s immunogenicity and increase the anti-tumor CD8+ T cell response.
AVEO Announces Exclusive Worldwide License Agreement for the Development and Commercialization of AV-380 and Related Antibodies
On August 17, 2015 AVEO Oncology (NASDAQ:AVEO) reported an exclusive, worldwide license agreement with Novartis for the development and commercialization of AVEO’s first-in-class, potent, humanized inhibitory antibody targeting growth differentiation factor 15 (GDF15), AV-380, and related antibodies, including modified or derivative forms of any such antibody (the "Product") (Press release, AVEO, AUG 17, 2015, View Source;p=irol-newsArticle&ID=2079881 [SID:1234512505]).
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Under the terms of the agreement, AVEO will receive an upfront payment of $15 million and will be eligible to receive reimbursement, clinical, sales and regulatory-based milestone payments totaling $311 million assuming successful advancement of the Product. AVEO will also be eligible to receive tiered royalties on product sales ranging from high single digits to a low double-digit. Novartis will be responsible for all clinical development, manufacturing and commercialization activities and costs associated with the Product.
"AV-380 holds great promise as a potential treatment for cachexia secondary to multiple disease states, including cancer, chronic kidney disease, congestive heart failure and chronic obstructive pulmonary disease," said Michael Bailey, AVEO’s president and chief executive officer. "Novartis brings resources and expertise to bear on advancing this program, which we believe provides the optimal path forward toward realizing its full potential."
About Cachexia and GDF15
Cachexia is a complex metabolic syndrome associated with malnutrition and severe involuntary weight loss due to the loss of muscle and fat tissue, as well as the clinical manifestation of anemia, inflammation and suppression of immune functions. Cachexia is a serious and common complication in patients with advanced cancer and other chronic diseases. It affects some five million individuals in the United States¹.
GDF15 is a pro-inflammatory cytokine whose elevated circulating levels have been correlated with cachexia in cachectic cancer patients and several animal models of cancer cachexia. Current evidence suggests that a pro-inflammatory state may be responsible for many of the symptoms associated with cachexia. Preclinical data show that inhibition of GDF15 results in a switch from catabolism to anabolism, suggesting that GDF15 inhibition with AV-380 may reverse the effects of cachexia.
6-K – Report of foreign issuer [Rules 13a-16 and 15d-16]
On August 17, 2015 BioLineRx Ltd. (NASDAQ: BLRX; TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported the initiation of a Phase 2b trial for BL-8040 as a novel consolidation treatment for acute myeloid leukemia (AML) (Filing, 6-K, BioLineRx, AUG 17, 2015, View Source [SID:1234507267]). The Phase 2b study will examine BL-8040 as part of a second stage treatment, termed consolidation therapy, to improve outcomes for AML patients who have achieved remission after the standard initial treatment regimen, known as induction therapy. The consolidation therapy is aimed at eliminating the minimal residual disease left in the bone marrow after induction therapy that can lead to relapse. This study is the first of three clinical studies in additional indications for BL-8040 which BioLineRx plans to commence during 2015, thus significantly expanding its unique BL-8040 oncology platform.
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Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx, stated, "The majority of high-risk AML patients achieving first complete remission relapse within one year, despite the current standard consolidation therapy. Patients with AML relapse have a poor prognosis despite further therapy, and less than 10% of these patients are cured by conventional therapy. Leukemic stem cells that are dormant in the bone marrow are presumed to be a major reason for AML relapse. Based on the pre-clinical and clinical data accumulated to date, BL-8040 is anticipated to boost the efficacy of consolidation therapy due to its dual mechanism of action. Firstly, BL-8040 induces mobilization of leukemic cells from the bone marrow, which enhances the cytotoxic effects of chemotherapy, and secondly, it possesses anti-leukemic pro-apoptotic properties that help eliminate AML cells directly. Based on positive results from our ongoing phase 2 clinical trial for BL-8040, which show substantial mobilization of AML cells from the bone marrow to the peripheral blood, as well as robust induction of AML cell apoptosis, we believe BL-8040 will be a promising addition to consolidation therapy for AML patients."
Dr. Savitsky added, "In addition to initiation of the Phase 2b AML consolidation study, we are eagerly looking forward to the top-line results from our ongoing Phase 2 study of BL-8040 for treating relapsed and refractory AML patients, which we expect in the fourth quarter of 2015. We also look forward to the next stages of development for BL-8040 as a novel stem cell mobilization treatment, after its recent successful completion of a Phase 1 trial. Finally, we are also excited about the anticipated initiation of clinical studies for BL-8040 in two additional indications over the next few months, thus further expanding and enhancing the potential of our oncology platform."
The Phase 2b trial, which is conducted in collaboration with the University of Halle as sponsor and with the participation of two large leukemia study groups in Germany, is a double-blind, placebo-controlled, randomized, multi-center study aimed at assessing the efficacy of BL-8040 in addition to standard consolidation therapy in AML patients. The primary endpoint of the study is to compare the relapse free survival (RFS) time in AML subjects in their first remission during a minimum follow-up time of 18 months after randomization. In addition, pharmacodynamic measurements will be conducted in order to assess the minimal residual disease, and biomarker analyses will be performed to identify predictors of BL-8040 response. The study will enroll up to 194 patients at up to 25 sites in Germany. AML patients between 18 and 75 years of age with documented first remission will be randomized in a 1:1 ratio to receive high dose Cytarabine, either with BL-8040 or with a matching placebo, as consolidation therapy.
About BL-8040
BL-8040 is a clinical-stage drug candidate for the treatment of acute myeloid leukemia, as well as other hematological indications. It is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis (growth of new blood vessels in the tumor), metastasis (spread of the disease to other organs or organ parts) and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a Phase 1/2, open-label, dose escalation, safety and efficacy clinical trial in 18 multiple myeloma patients, BL-8040, when combined with G-CSF, demonstrated an excellent safety profile at all doses tested and was highly effective in the mobilization of hematopoietic stem cells and white blood cells from the bone marrow to the peripheral blood. Additionally, in a Phase 1 stem-cell mobilization study in healthy volunteers, BL-8040 as a single agent was safe and well tolerated at all doses tested and resulted in efficient stem-cell mobilization and collection in all study participants. Importantly, the results of this study support the use of BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care.
BL-8040 also mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer effect by inducing apoptosis. Pre-clinical studies show that BL-8040 inhibits the growth of various tumor types including multiple myeloma, non-Hodgkin’s lymphoma, leukemia, non-small cell lung carcinoma, neuroblastoma and melanoma. BL-8040 significantly and preferentially stimulated apoptotic cell death of malignant cells (multiple myeloma, non-Hodgkin’s lymphoma and leukemia). Significant synergistic and/or additive tumor cell killing activity has been observed in-vitro and in-vivo when tumor cells were treated with BL-8040 together with Rituximab, Bortezomib, Imatinib, Cytarabine and the FLT-3 inhibitor AC-220 (in NHL, MM, CML, AML, and AML-FLT3-ITD models, respectively). In addition, the current Phase 2 clinical trial in AML patients has demonstrated robust mobilization and apoptosis of cancer cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.
About Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. According to the American Cancer Society, approximately 19,000 new cases of AML were diagnosed in the United States in 2014, and the median age of AML patients was 67 years old. The first treatment line for patients with AML includes a combination of chemotherapy drugs and is called induction treatment. The median survival for AML patients receiving induction chemotherapy is less than two years, with shorter survival for patients over the age of 60 or for those with certain gene or chromosome aberrations. Due to relapsed or refractory disease (where the disease is not responsive to standard treatments), the overall five-year survival rate for AML is between 10 and 40 percent.