A research assistant position is immediately available in December in the Department of Immunology and Microbial Science at The Scripps Research Institute, La Jolla. The successful candidate will be responsible for conducting experiments in mouse gen […
Late-Breaking Ibrutinib (IMBRUVICA®) Data Show Complete or Partial Response in Two-Thirds of Patients with Chronic Graft-Versus-Host-Disease, a Frequent and Potentially Life-Threatening Complication of Stem Cell Transplant
– New Phase 2 data presented at the American Society of Hematology Annual Meeting highlight potential role of ibrutinib therapy beyond hematologic cancers- The study found an overall response rate of 67%- This release corresponds to abstract #LBA-3
NORTH CHICAGO, Ill., Dec. 6, 2016 /PRNewswire/ — AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced positive results from a Phase 2 study (PCYC-1129) evaluating ibrutinib (IMBRUVICA®) in patients with chronic graft-versus-host-disease (cGVHD), a serious and debilitating potential consequence of stem cell or bone marrow transplant,1 who failed prior systemic therapy. The study found ibrutinib demonstrated efficacy, sustained responses and reduced symptom severity, with an overall response rate (ORR) of 67%.2 Final results from this study presented today as a late-breaking oral presentation at the 58th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA (abstract #LBA-3). IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
At a median follow-up of 14 months in 42 patients, the study found an ORR of 67%. One-third of all responders achieved a complete response (CR). In addition, 71% of patients showed a sustained response of at least 5 months. Similar response rates were seen across all involved organs, and patients with multiple organ involvement generally responded in multiple organs. Over the course of the study, 61% of responders experienced a clinically meaningful improvement in symptoms, as measured by at least a 7-point decrease in Lee Symptom Scale score. In addition, 62% of all patients were able to reduce steroid dose to an acceptable minimal level and five completely discontinued steroids with response. Twelve patients (29%) remain on treatment with ibrutinib.2
“These results are encouraging as they suggest ibrutinib has clinically meaningful potential in patients with steroid-refractory chronic graft-versus-host-disease,” said David Miklos, M.D., Ph.D., Associate Professor of Medicine (Blood and Marrow Transplantation), Stanford University and lead investigator of the study.* “cGVHD patients face a challenging treatment journey with the majority of patients being prescribed steroids, with which long-term use can lead to serious health complications. With no FDA-approved therapies available specifically for cGVHD, new treatment options are critically needed.”
GVHD is a life-threatening condition in which the body is attacked by donor immune cells after a patient undergoes an allogeneic stem cell or bone marrow transplant.1,3 GVHD can be acute or chronic; chronic GVHD (cGVHD) usually starts more than 3 months after a transplant and can last many years.3 Symptoms can include skin problems, hair loss, mouth sores, eye irritation, severe lung injury, or liver dysfunction.3 There are currently no therapies specifically approved for patients with cGVHD who have failed first-line corticosteroid therapy and require additional therapy. Most patients with cGVHD are prescribed high dose glucocorticoids, a systemic steroid that suppresses the immune system and is associated with substantial morbidity and relapse of the underlying disease.3
“Ibrutinib works as a BTK inhibitor, which is showing to have a potential impact beyond blood cancers, including chronic graft-versus-host-disease,” said Lori Styles, M.D., Senior Medical Director and GVHD program clinical lead at Pharmacyclics LLC, an AbbVie company. “We recognize the critical need for new treatments for patients with cGVHD and are encouraged by the results of this well-designed study, giving us confidence to proceed with a Phase 3 trial evaluating the impact of ibrutinib as part of initial therapy for this severe and potentially life-threatening condition. We are committed to exploring the full potential of ibrutinib in a range of health conditions with unmet needs.”
The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation and Orphan Drug Designation in June 2016 for ibrutinib as a potential treatment for cGVHD after failure of one or more lines of systemic therapy.
About the Study
PCYC-1129 evaluated the safety and efficacy of ibrutinib in 42 patients (median age 56 years) with cGVHD who failed at least one prior therapy, including corticosteroids. Patients were treated with ibrutinib once daily until cGVHD progression or unacceptable toxicity. The primary endpoint was cGVHD response based on the National Institutes of Health (NIH) consensus response criteria. Secondary endpoints included rate of sustained response, change in Lee cGVHD Symptom Scale, changes in corticosteroid requirement over time, and safety endpoints. Overall, reported adverse events (AEs) were consistent with those treated with ibrutinib for B-cell malignancies and in patients with cGVHD on corticosteroids.2
The most common AEs were fatigue (57%), diarrhea (36%), muscle spasms (29%), nausea (26%), and bruising (24%). Serious AEs (SAEs) occurred in 22 patients (52%), including pneumonia (n=6), septic shock (n=2), and pyrexia (n=2).2
Preliminary results from this trial were previously presented at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (ESBM) in April 2016 and the 51st American Society of Clinical Oncology (ASCO) Annual Meeting in May 2015.
IMBRUVICA is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.4,5 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.4
IMBRUVICA is approved to treat patients with CLL/SLL including patients with 17p deletion, patients with MCL who have received at least one prior therapy and patients with WM. Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials. 4
IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway.
IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry with nearly 30 (n=27) company-sponsored trials underway, 14 of which are Phase 3. In addition, there are more than 40 (n=44) investigator-sponsored trials taking place around the world. To date, more than 65,000 patients around the world have been treated with IMBRUVICA in clinical practice and in clinical trials.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA®. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA®.
The mechanism for the bleeding events is not well understood. IMBRUVICA® may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.
Infections – Fatal and nonfatal infections have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA®. Evaluate patients for fever and infections and treat appropriately.
Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA®. Monitor complete blood counts monthly.
Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA®, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA® treatment and follow dose modification guidelines.
Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA® with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA®. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.
Second Primary Malignancies – Other malignancies (range, 5% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4% to 13%).
Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA® therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.
Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA® and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, and WM) were neutropenia** (64%), thrombocytopenia** (63%), diarrhea (43%), anemia**(41%), musculoskeletal pain (30%), rash (29%), nausea (29%), bruising (29%), fatigue (27%), hemorrhage (21%), and pyrexia 21%).
**Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).
The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%). Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.
Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most frequent adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash and neutropenia (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.
CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA® dose.
CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.
Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA® dose.
Please see Full Prescribing Information: https://www.imbruvica.com/prescribing-information
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world’s most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words “believe,” “expect,” “anticipate,” “project” and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie’s operations is set forth in Item 1A, “Risk Factors,” in AbbVie’s 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
IMBRUVICA is a registered trademark of Pharmacyclics LLC.
*Disclaimer: Dr. Miklos served as an investigator of this Pharmacyclics-sponsored clinical study. Dr. Miklos does not have a financial interest in the company.
1 MedlinePlus, U.S. National Library of Medicine. Graft-versus-host-disease. Available from: http://www.nlm.nih.gov/medlineplus/ency/article/001309.htm. Accessed March 2016.
2 Miklos, D, et al. Multicenter Open-Label Phase 2 Study of Ibrutinib in Chronic Graft Versus Host Disease (cGVHD) After Failure of Corticosteroids. ASH 2016 Abstract #LBA-3.
3 The Leukemia and Lymphoma Society. Graft Versus Host Disease. Available from: http://www.lls.org/treatment/types-of-treatment/stem-cell-transplantation/graft-versus-host-disease.
4 IMBRUVICA US Prescribing Information, May 2016.
5 Genetics Home Reference. Isolated growth hormone deficiency. Available from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed May 2016.
Mast Therapeutics Announces Initiation Of Patient Enrollment In Additional Phase 2 Study Of AIR001 For The Treatment Of Heart Failure With Preserved Ejection Fraction
SAN DIEGO, Dec. 6, 2016 /PRNewswire/ — Mast Therapeutics, Inc. (NYSE MKT: MSTX) today reported that the first patient has been enrolled in an investigator-sponsored Phase 2 study of the Company’s lead product candidate, AIR001, for the treatment of heart failure with preserved ejection fraction (HFpEF). The Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training (INABLE-TRAINING) in HFpEF study will evaluate AIR001’s potential to improve the clinical responses to exercise training in individuals with HFpEF. The INABLE-TRAINING study is expected to enroll approximately 68 patients who will undergo 12 weeks of cardiac rehabilitation, including exercise training, and will be randomized to receive either AIR001 or placebo inhalation solution through the training period. The primary endpoint of the study will be the change in exercise capacity as measured by peak oxygen consumption.
“We are pleased to report that patient enrollment is underway in this Phase 2 study of AIR001 for the treatment of HFpEF,” stated Brian M. Culley, Chief Executive Officer of Mast Therapeutics, Inc. “There are now three Phase 2 studies actively enrolling patients to evaluate AIR001 for the treatment of HFpEF and we remain excited about its potential in this indication. Data from this and other studies will help guide our clinical and regulatory strategy in this area of significant unmet need. Currently, HFpEF affects approximately half of the more than 5 million people in the U.S. diagnosed with heart failure and has no proven effective treatment. Heart failure is a leading cause of morbidity and mortality among the elderly worldwide and is the primary diagnosis in more than 1 million hospitalizations each year, with medical costs projected to rise to more than $50 billion in the U.S. alone by 2030.”
About the INABLE-TRAINING Study
This is a Phase 2 randomized, double-blind, parallel-group placebo-controlled clinical trial testing whether inhaled AIR001 (sodium nitrite solution), as compared to inhaled placebo, can enhance the benefits from chronic exercise training (ET) in subjects with HFpEF. All subjects will undergo 12 weeks of ET. Participants will be randomized to receive inhaled AIR001 three times daily or inhaled sodium chloride (placebo) three times daily during the study period. Study subjects will wear accelerometry devices to track daily activity levels at home. After 12 weeks of ET as part of standard cardiac rehab, subjects will repeat the assessment of cardiovascular function and exercise capacity as performed at study entry to assess efficacy at a final visit.
The Phase 2 study has 2 aims. First, determine whether treatment with inhaled AIR001 in addition to ET for 12 weeks improves exercise capacity and hemodynamic reserve in HFpEF. Expired gas analysis, inert gas (C2H2) rebreathe, and echocardiography will be performed during rest and exercise to measure oxygen consumption (VO2), CO, and hemodynamics before and after completion of 12 weeks of ET with inhaled NO2- vs ET with inhaled placebo. Second, determine whether treatment with inhaled AIR001 in addition to ET for 12 weeks increases daily activity levels and quality of life (QOL), and reduces symptoms of effort intolerance during ET. Subjects will use externally worn accelerometer devices to track daily physical activity. Tolerability of ET will be assessed by Borg perceived effort and dyspnea scores. Large and small vessel endothelial function (brachial and digital arteries) and QOL will also be assessed. Secondary endpoints include cardiac output reserve, peak exercise workload, rest and exercise hemodynamics assessed by echocardiography, Borg dyspnea and fatigue scores recorded during ET, endothelial function assessed by tonometry and brachial artery flow mediated dilation, QOL assessed by the Kansas City Cardiomyopathy Questionnaire. (ClinicalTrials.gov Identifier: NCT02713126)
AIR001 is a sodium nitrite solution for intermittent inhalation via nebulization. Nitrite is a direct vasodilator and can be recycled in vivo to form nitric oxide (NO) independent of the classical NO synthase (NOS) pathway. Nitrite mediated NO formation has several beneficial effects, including dilation of blood vessels and reduction of inflammation and undesirable cell growth. Generation of NO from sodium nitrite is not dependent upon endothelial function and is enhanced in the setting of tissue hypoxia and acidosis, conditions in which NOS activity typically is depressed. In early clinical studies, AIR001 demonstrated positive hemodynamic effects with reductions observed in right atrial pressure and pulmonary capillary wedge pressure, as well as improvements in mean pulmonary artery pressures, cardiac output, and exercise tolerance as measured by six-minute walk distance. In a randomized, double-blind, placebo-controlled Phase 2a study of AIR001 in patients with heart failure with preserved ejection fraction (HFpEF) (n=26), the AIR001 treatment group showed a statistically significant decrease in pulmonary capillary wedge pressure during exercise compared to the control group and AIR001 was generally well-tolerated.
About Mast Therapeutics
Mast Therapeutics, Inc. is a publicly traded biopharmaceutical company headquartered in San Diego, California. The Company has two clinical-stage investigational new drugs, AIR001 and vepoloxamer. AIR001, a sodium nitrite solution for intermittent inhalation via nebulization, is in Phase 2 clinical development for the treatment of heart failure with preserved ejection fraction (HFpEF). More information can be found on the Company’s web site at www.masttherapeutics.com. Mast Therapeutics™ and the corporate logo are trademarks of Mast Therapeutics, Inc.
Forward Looking Statements
Mast Therapeutics cautions you that statements in this press release that are not a description of historical fact are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words referencing future events or circumstances such as “expect,” “intend,” “plan,” “anticipate,” “believe,” and “will,” among others. Examples of forward-looking statements in this press release include statements relating to AIR001’s potential to treat HFpEF, the timing of completion of any clinical studies, and the Company’s development plans for AIR001. Forward-looking statements should not be read as guarantees of future performance or results because they involve the Company’s beliefs and assumptions based on currently available information and are subject to significant known and unknown risks and uncertainties that may cause actual performance and results to differ materially from expectations indicated by the forward-looking statements. Some of the factors that could cause actual performance or results to differ include, without limitation: the Company’s need for additional funding and the risk that it may not be able to obtain sufficient additional funding as needed; risks associated with the Company’s ability to manage operating expenses; uncertainty related to the Company’s ability to continue to operate as a going concern; risk of an event of default under the Company’s debt facility that could result in the Company being required to repay its outstanding debt obligation and related fees on an accelerated basis and/or at a time that could be detrimental to the Company’s financial condition, operations and/or business strategy; the impact of significant reductions in the Company’s operations on its ability to develop its product candidates or maintain compliance with laws and regulations relating to public companies; the Company’s ability to maintain compliance with NYSE MKT continued listing standards and policies and to maintain the listing and trading of its common stock on a national securities exchange; uncertainties inherent in the conduct of clinical studies and the risk that the Company’s product candidates may not demonstrate adequate safety, efficacy or tolerability in one or more clinical studies for approval by regulatory authorities; the Company’s lack of control over investigator-sponsored clinical studies of AIR001, including whether any of the studies will commence or be completed on anticipated timelines, or at all; the potential for the Company to sell or license part or all of its assets; the potential for significant delays, reductions, or discontinuation of current and/or planned development activities if the Company is unable to raise sufficient additional capital as needed; the Company’s dependence on third parties to assist with important aspects of development of the Company’s product candidates, including the conduct of clinical and nonclinical studies, the manufacture and supply of clinical trial material, including drug delivery devices, and the conduct of regulatory activities, and the risk that such third parties may fail to perform as expected leading to delays in product candidate development and additional costs; the risk that the Company is not able to obtain or maintain effective patent coverage or other market exclusivity protections for its products, if approved, or that the use or manufacture of the Company’s products may infringe the proprietary rights of others; and other risks and uncertainties more fully described in the Company’s press releases and its reports filed with the Securities and Exchange Commission. The Company’s public filings with the Securities and Exchange Commission are available at www.sec.gov.
You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date when made. Mast Therapeutics does not intend to revise or update any forward-looking statement set forth in this press release to reflect events or circumstances arising after the date hereof, except as may be required by law.
SOURCE Mast Therapeutics, Inc.
New Analysis Shows People with Cancer Who Received XARELTO® (rivaroxaban) for Blood Clots Had Fewer ER Visits and Lower Healthcare Costs than Those Given Standard Treatment
Findings align with the ongoing CALLISTO clinical research programEconomic and real-world research for XARELTO® in cancer-associated thrombosis (CAT) among other studies presented confirming the medicine’s safety and efficacy profile
SAN DIEGO, Dec. 6, 2016 /PRNewswire/ — A new analysis shows people with cancer treated with XARELTO® (rivaroxaban) for blood clots had significantly fewer emergency room (ER) visits and lower healthcare costs at initiation of therapy than those given standard treatment. The analysis presented this week by Janssen Pharmaceuticals, Inc. (Janssen) and its development partner, Bayer, at the 2016 American Society of Hematology (ASH) Annual Meeting examines the use of XARELTO® in cancer-associated thrombosis, an area of critical unmet need. Also presented were economic research and real-world evidence confirming the overall safety and efficacy profile of XARELTO® in this patient group.
Blood clots, or venous thromboembolisms (VTE), are the second leading cause of death in people with cancer. The risk of VTE in people with cancer is up to five times higher than in people the same age without cancer, and magnifies in those receiving certain types of chemotherapy. The current standard of care for treating cancer-associated blood clots is low-molecular-weight heparin (LMWH), an injectable anticoagulant.
“Standard therapy for cancer-associated blood clots is burdensome for patients who endure daily painful injections. It also incurs considerable costs for healthcare systems throughout the entire treatment process,” said Gerald A. Soff, MD, Chief, Hematology Service, Memorial Sloan Kettering Cancer Center, New York, NY, and CALLISTO principal investigator. “This study found the majority of people with cancer treated with rivaroxaban did not require an ER visit to initiate therapy, thus sparing costly healthcare resources.”
According to the analysis, fewer people had to go to the ER to start treatment with XARELTO® than LMWH, demonstrating significant changes in practice and cost savings. In the first six months of the study, similar rates of people were sent to the ER to start anticoagulation treatment between the XARELTO® and LMWH* groups (71% vs. 63%, respectively). After those six months, there was a significant decrease in people starting treatment with XARELTO® in the ER from 71% at baseline to 42% at one year (p=0.008) and 34% at 18 months (p=0.0001), which researchers attributed to physicians becoming more familiar with XARELTO®. After one year, 18% of people who were prescribed XARELTO® were managed by a simple telephone call, typically after a recent outpatient visit. Researchers also observed significant cost savings for people taking XARELTO®, which was mainly due to the reduction in ER visits.
The start of anticoagulation treatment was classified in one of four ways: an ER visit, a second return outpatient visit on the same day, a single outpatient visit or a telephone communication. Patients whose VTE developed as an inpatient were excluded.
This economic analysis stems from an investigator-initiated study, which followed patients with active cancer who were newly diagnosed with VTE and treated with either XARELTO® or the LMWH enoxaparin. Investigators noted there was no evidence of loss of safety or efficacy in the analysis.
*LMWH data were only collected once in the six months prior to the first XARELTO® period.
Other Economic Cancer-Associated Thrombosis Research
Other economic data presented at ASH found that people newly diagnosed with cancer who experienced a VTE recurrence (17.1% of 2,428 patients) utilized significantly more healthcare resources (defined as ER visits, outpatient visits, hospitalizations and hospital days) than those who did not have a VTE recurrence. Baseline total healthcare costs were similar for both groups.
A companion study found VTE-related healthcare resource utilization was lowest in people with cancer receiving XARELTO® compared to those receiving LMWH or warfarin. Healthcare costs were also lower in the XARELTO® group compared to the LWMH group and similar between the XARELTO® and warfarin groups. Both studies evaluated claims data from the U.S. Humana database.
“Data presented at this conference and earlier this year support an enhanced role for rivaroxaban in cancer patients, particularly given its value in reducing the burden of care on patients and resources for health systems. Ongoing large randomized trials will aim to further clarify this role and help reduce the public health impact of cancer-associated thrombosis,” said Alok Khorana, MD, FACP, Sondra and Stephen Hardis Chair in Oncology, Vice Chair for Clinical Services, Director of the GI Malignancies Program, Cleveland Clinic, Cleveland, OH. Dr. Khorana is compensated by Janssen for his role as chair of the CALLISTO advisory council and co-chair of the VTE prevention study steering committee.
Additional CAT Research at ASH
In addition to economic research, new real-world studies confirming the safety and efficacy profile of XARELTO® in people with cancer were presented at ASH:
- A subgroup analysis of XALIA, a Phase 4, prospective, non-interventional, observational study, found people with cancer who switched to treatment with XARELTO® for VTE had the lowest rates of all-cause mortality and major bleeding. Highest rates were observed in those taking standard anticoagulation (heparin/fondaparinux and a vitamin K antagonist, or a vitamin K antagonist alone) for major bleeding, and in those taking heparin/fondaparinux for recurrent VTE and all-cause mortality.
- An analysis of Janssen’s ongoing post-marketing safety surveillance study (PMSS) for VTE, found the incidence of major bleeding to be relatively low and similar between people with cancer (active or a history of) and those without cancer. More than 10 million electronic medical records from the U.S. Department of Defense Military Health System were queried to evaluate the safety of XARELTO® for the treatment of VTE. This analysis included 9,638 patients with VTE: 17.9% with active cancer, 16.1% with a history of cancer, and 66% with no cancer. PMSS is a retrospective study with no comparator arm.
“These studies presented at ASH may play an important role in reducing the significant economic burden of cancer-associated blood clots,” said Paul Burton, MD, PhD, FACC, Vice President, Medical Affairs, Janssen. “We continue to explore the potential and benefits of XARELTO® as a treatment alternative for patients in this area of critical medical need.”
About CALLISTO and EXPLORER
The CALLISTO research program is the largest and broadest prospective clinical program evaluating a non-vitamin K antagonist oral anticoagulant (NOAC), specifically XARELTO®, for the prevention and treatment of cancer-associated blood clots. CALLISTO, which includes clinical trials and registries in more than 4,000 patients, is evaluating XARELTO® for the prevention and treatment of blood clots in people with a wide range of cancer types. It builds on prior findings from the Phase 3 EINSTEIN clinical program, which was used by regulatory authorities worldwide to approve XARELTO®.
CALLISTO is an integral part of Janssen and Bayer’s broader EXPLORER clinical research program for XARELTO®. Unmatched by any oral anticoagulant in the NOAC class in its size, scope and ambition, EXPLORER continues to generate important clinical evidence on the safety and efficacy performance of XARELTO® and its potential role in addressing additional critical medical needs. By the time of its completion, more than 275,000 patients will have participated in EXPLORER, which includes ongoing and completed studies, independent registries and non-interventional studies. The EXPLORER program includes six additional indication-seeking programs underway beyond the currently approved six indications in the U.S.
WHAT IS XARELTO®?
XARELTO® is a prescription medicine used to reduce the risk of stroke and blood clots in people with atrial fibrillation, not caused by a heart valve problem. For patients currently well managed on warfarin, there is limited information on how XARELTO® and warfarin compare in reducing the risk of stroke.
XARELTO® is also a prescription medicine used to treat deep vein thrombosis and pulmonary embolism, and to help reduce the risk of these conditions occurring again.
XARELTO® is also a prescription medicine used to reduce the risk of forming a blood clot in the legs and lungs of people who have just had knee or hip replacement surgery.
IMPORTANT SAFETY INFORMATION
WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT XARELTO®?
- For people taking XARELTO® for atrial fibrillation:
People with atrial fibrillation (an irregular heart beat) are at an increased risk of forming a blood clot in the heart, which can travel to the brain, causing a stroke, or to other parts of the body. XARELTO® lowers your chance of having a stroke by helping to prevent clots from forming. If you stop taking XARELTO®, you may have increased risk of forming a clot in your blood.
Do not stop taking XARELTO® without talking to the doctor who prescribes it for you. Stopping XARELTO® increases your risk of having a stroke.
If you have to stop taking XARELTO®, your doctor may prescribe another blood thinner medicine to prevent a blood clot from forming.
- XARELTO® can cause bleeding, which can be serious, and rarely may lead to death. This is because XARELTO® is a blood thinner medicine that reduces blood clotting. While you take XARELTO® you are likely to bruise more easily and it may take longer for bleeding to stop.
You may have a higher risk of bleeding if you take XARELTO® and take other medicines that increase your risk of bleeding, including:
- Aspirin or aspirin-containing products
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Warfarin sodium (Coumadin®, Jantoven®)
- Any medicine that contains heparin
- Clopidogrel (Plavix®)
- Selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs)
- Other medicines to prevent or treat blood clots
Tell your doctor if you take any of these medicines. Ask your doctor or pharmacist if you are not sure if your medicine is one listed above.
Call your doctor or get medical help right away if you develop any of these signs or symptoms of bleeding:
- Unexpected bleeding or bleeding that lasts a long time, such as:
- Nosebleeds that happen often
- Unusual bleeding from gums
- Menstrual bleeding that is heavier than normal, or vaginal bleeding
- Bleeding that is severe or that you cannot control
- Red, pink, or brown urine
- Bright red or black stools (looks like tar)
- Cough up blood or blood clots
- Vomit blood or your vomit looks like “coffee grounds”
- Headaches, feeling dizzy or weak
- Pain, swelling, or new drainage at wound sites
Spinal or epidural blood clots (hematoma): People who take a blood thinner medicine (anticoagulant) like XARELTO®, and have medicine injected into their spinal and epidural area, or have a spinal puncture, have a risk of forming a blood clot that can cause long-term or permanent loss of the ability to move (paralysis). Your risk of developing a spinal or epidural blood clot is higher if:
- A thin tube called an epidural catheter is placed in your back to give you certain medicine
- You take NSAIDs or a medicine to prevent blood from clotting
- You have a history of difficult or repeated epidural or spinal punctures
- You have a history of problems with your spine or have had surgery on your spine
If you take XARELTO® and receive spinal anesthesia or have a spinal puncture, your doctor should watch you closely for symptoms of spinal or epidural blood clots. Tell your doctor right away if you have back pain, tingling, numbness, muscle weakness, (especially in your legs and feet), or loss of control of the bowels or bladder (incontinence).
XARELTO® is not for patients with artificial heart valves.
WHO SHOULD NOT TAKE XARELTO®?
Do not take XARELTO® if you:
- Currently have certain types of abnormal bleeding. Talk to your doctor before taking XARELTO® if you currently have unusual bleeding.
- Are allergic to rivaroxaban or any of the ingredients of XARELTO®.
WHAT SHOULD I TELL MY DOCTOR BEFORE OR WHILE TAKING XARELTO®?
Before taking XARELTO®, tell your doctor if you:
- Have ever had bleeding problems
- Have liver or kidney problems
- Have any other medical condition
- Are pregnant or plan to become pregnant. It is not known if XARELTO® will harm your unborn baby. Tell your doctor right away if you become pregnant while taking XARELTO®. If you take XARELTO® during pregnancy, tell your doctor right away if you have bleeding or symptoms of blood loss.
- Are breastfeeding or plan to breastfeed. It is not known if XARELTO® passes into your breast milk. You and your doctor should decide if you will take XARELTO® or breastfeed.
Tell all of your doctors and dentists that you are taking XARELTO®. They should talk to the doctor who prescribed XARELTO® for you before you have any surgery, medical or dental procedure.
Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Some of your other medicines may affect the way XARELTO® works. Certain medicines may increase your risk of bleeding. See “What is the most important information I should know about XARELTO®?”
Especially tell your doctor if you take:
- Ketoconazole (Nizoral®)
- Itraconazole (Onmel™, Sporanox®)
- Ritonavir (Norvir®)
- Lopinavir/ritonavir (Kaletra®)
- Indinavir (Crixivan®)
- Carbamazepine (Carbatrol®, Equetro®, Tegretol®, Tegretol®-XR, Teril™, Epitol®)
- Phenytoin (Dilantin-125®, Dilantin®)
- Phenobarbital (Solfoton™)
- Rifampin (Rifater®, Rifamate®, Rimactane®, Rifadin®)
- St. John’s wort (Hypericum perforatum)
Ask your doctor if you are not sure if your medicine is one listed above. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
HOW SHOULD I TAKE XARELTO®?
Take XARELTO® exactly as prescribed by your doctor.
Do not change your dose or stop taking XARELTO® unless your doctor tells you to.
- Your doctor will tell you how much XARELTO®to take and when to take it.
- Your doctor may change your dose if needed.
If you take XARELTO® for:
- Atrial Fibrillation: Take XARELTO® 1 time a day with your evening meal.
If you miss a dose of XARELTO®, take it as soon as you remember on the same day. Take your next dose at your regularly scheduled time.
- Blood clots in the veins of your legs or lungs:
- Take XARELTO® once or twice a day as prescribed by your doctor.
- Take XARELTO® with food at the same time each day.
- If you miss a dose of XARELTO®:
- and take XARELTO® 2 times a day: Take XARELTO® as soon as you remember on the same day. You may take 2 doses at the same time to make up for the missed dose. Take your next dose at your regularly scheduled time.
- and take XARELTO® 1 time a day: Take XARELTO® as soon as you remember on the same day. Take your next dose at your regularly scheduled time.
- Hip or knee replacement surgery: Take XARELTO® 1 time a day with or without food. If you miss a dose of XARELTO®, take it as soon as you remember on the same day. Take your next dose at your regularly scheduled time.
- If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take XARELTO®.
- Your doctor will decide how long you should take XARELTO®. Do not stop taking XARELTO®without talking to your doctor first.
- Your doctor may stop XARELTO® for a short time before any surgery, medical or dental procedure. Your doctor will tell you when to start taking XARELTO® again after your surgery or procedure.
- Do not run out of XARELTO®. Refill your prescription for XARELTO® before you run out. When leaving the hospital following a hip or knee replacement, be sure that you have XARELTO® available to avoid missing any doses.
- If you take too much XARELTO®, go to the nearest hospital emergency room or call your doctor right away.
WHAT ARE THE POSSIBLE SIDE EFFECTS OF XARELTO®?
Please see “What is the most important information I should know about XARELTO®?”
Tell your doctor if you have any side effect that bothers you or that does not go away.
Call your doctor for medical advice about side effects. You are also encouraged to report side effects to the FDA: visit http://www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Janssen Pharmaceuticals, Inc., at 1-800-JANSSEN (1-800-526-7736).
Please click here for full Prescribing Information, including Boxed Warnings, and Medication Guide.
Trademarks are those of their respective owners.
Janssen and Bayer together are developing rivaroxaban.
For more information about XARELTO®, visit www.xarelto.com.
About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us on Twitter at @JanssenUS.
Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development, including the impact of ongoing clinical research programs and benefits of rivaroxaban. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Pharmaceuticals, Inc., any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges inherent in product research and development, including uncertainty of clinical success and obtaining regulatory approvals; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended January 3, 2016, including in Exhibit 99 thereto, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
Investor Relations Contacts:
Johnson & Johnson
Joseph J. Wolk
SOURCE Janssen Pharmaceuticals, Inc.
NEW HAVEN, Conn., Dec. 6, 2016 /PRNewswire/ — Arvinas LLC, a private biotechnology company creating a new class of drugs known as PROTACs which function via targeted protein degradation, today announced that preclinical data were presented by three Arvinas collaborators at the 2016 American Society of Hematology (ASH) Annual Meeting in San Diego, CA. The data presented demonstrate superior efficacy of PROTACs targeting the BET (bromodomain and extraterminal domain) protein family when compared to BET inhibitors in preclinical models of lymphoma and leukemia.
“The data further support our ongoing understanding of how the Arvinas BET PROTACs show pronounced efficacy improvements compared to BET inhibitors in in vitro and in vivo model systems. The advantages of BET degradation have now been demonstrated preclinically in a number of solid tumor and hematologic cancers including diffuse large B cell lymphoma, prostate cancer, ovarian cancer, mantle cell lymphoma and acute myeloid leukemia (AML),” said Manuel Litchman, M.D., President and CEO of Arvinas.
“These findings underscore the superior activity of BET PROTACs versus BET inhibitors against mantle cell lymphoma cells that are either sensitive or resistant to the drug ibrutinib, as well as against models of AML,” said Kapil Bhalla, M.D., Professor of Leukemia at the University of Texas MD Anderson Cancer Center.
In a podium presentation titled “Novel BET PROTACs Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells” and presented by Dr. Bhalla, data show:
- Compared to BET inhibitors, in primary mantle cell lymphoma (MCL) cells and MCL cell lines, BET PROTACs provide greater down-regulation of the expression of genes important to tumor growth and survival, greater killing of cells resistant to ibrutinib and greater inhibition of the growth of ibrutinib-resistant MCL xenografts alone and in combination with rationally selected targeted agents.
Dr. Sujan Piya of the University of Texas MD Anderson Cancer Center presented data on Arvinas BET PROTAC ARV-825 in a podium presentation titled “BRD4 PROTAC ARV-825 Causes Sustained Degradation of BRD4 and Modulation of Chemokine Receptors, Cell Adhesion and Metabolic Targets in Leukemia Resulting in Profound Anti-Leukemic Effects.”
- As a single agent, ARV-825 demonstrated substantial activity across multiple models of AML, including cell lines, primary AML blasts and a mouse model of human leukemia.
- In all tested cell lines and primary cells, the BET PROTAC was significantly more potent than a BET inhibitor.
- Importantly, in a co-culture model, ARV-825 was shown to modulate the tumor microenvironment and metabolism to overcome stroma-mediated drug resistance.
Dr. Warren Fiskus of the University of Texas MD Anderson Cancer Center delivered a podium presentation titled “Superior Lethal Activity of Novel BET PROTAC Versus BET Inhibitor Against Post-Myeloproliferative Neoplasm Secondary AML Cells (sAML).”
- Arvinas BET PROTACs were significantly more potent than a BET inhibitor in inducing apoptosis-driven cell death of patient-derived and cultured secondary AML (sAML) cells and caused greater depletion of several key sAML signaling and survival proteins.
- Co-treatment of BET PROTAC ARV-825 and JAK inhibitor ruxolitinib showed synergistic lethality against sAML cells.
- Notably, BET PROTACs both alone and in combination with either an HSP90 inhibitor or a BCL2/BcL-xL antagonist were highly active against JAK inhibitor-resistant sAML cells.
- Compared to a BET inhibitor, treatment with BET-PROTAC ARV-771 significantly reduced leukemia growth and improved survival of mice engrafted with sAML cell xenografts.
Abstracts are available on the Arvinas website under Publications at www.arvinas.com.
Arvinas is a pharmaceutical company focused on developing new small molecules ‒ known as PROTACs (PROteolysis TArgeting Chimeras) ‒ aimed at degrading disease-causing cellular proteins. Based on groundbreaking research conducted at Yale University by Founder and Chief Scientific Advisor, Dr. Craig Crews, the company is translating innovative protein degradation approaches into novel drugs for the treatment of cancer and other diseases. The company’s new PROTAC-based drug paradigm induces protein degradation, rather than protein inhibition, and offers the advantage of potentially targeting “undruggable” as well as “druggable” elements of the proteome. This greatly expands the ability to create drugs for many new, previously unapproachable targets. For more information, visit www.arvinas.com.
Sutro ADC Targeting CD74 Exhibits Potent Anti-tumor Activity in Multiple Malignant Cell Lines and Animal Models of Non-Hodgkin Lymphoma and Multiple Myeloma
Sutro Launches IND-Enabling Studies of STRO-001 for Treatment of B-Cell Hematologic Malignancies
SOUTH SAN FRANCISCO, Calif., Dec. 6, 2016 /PRNewswire/ — Sutro Biopharma Inc. today announced that it has launched IND-enabling studies, including preparation for GLP toxicology, of STRO-001, an antibody drug conjugate, or ADC, that targets CD74, a protein highly expressed in B-cell malignancies. STRO-001 demonstrated efficient cell killing in multiple malignant B-cell lines and exhibited potent anti-tumor activity in six mouse tumor models of non-Hodgkin lymphoma and multiple myeloma, according to studies recently completed by Sutro.
Dr. Arturo Molina, a medical oncologist and Sutro’s chief medical officer, described the study findings this past Sunday in an oral presentation entitled “Targeting CD74 with Novel Antibody Drug Conjugates for the Treatment of B-Cell Non-Hodgkin’s Lymphoma” during a session on “Lymphoma – Pre-Clinical – Chemotherapy and Biologic Agents – Novel Therapeutic Strategies” at the annual meeting of the American Society of Hematology in San Diego. The Sutro STRO-001 research team presented additional findings yesterday in a poster entitled “Discovery and Preclinical Development of Novel CD74-Targeting Antibody-Drug Conjugates with Significant Activity in Multiple Myeloma Cell Lines and Xenograft Models,” at the ASH annual meeting.
“Based on these findings, we are launching IND-enabling and GLP toxicology studies of an ADC developed with Sutro’s proprietary cell-free protein synthesis and site-specific conjugation platforms, which facilitate multiple rounds of antibody and ADC optimization,” Sutro CEO Bill Newell said.
“With these data, we have encouraging preclinical evidence of CD74’s potential usefulness as an ADC target,” added Dr. Amrita Krishnan, Professor of Hematology and Hematopoietic Cell Transplantation, Director of the Judy and Bernard Briskin Center for Multiple Meyloma Research and Director of the Multiple Myeloma Program at the City of Hope Comprehensive Cancer Center.
Sutro’s novel ADCs efficiently killed multiple myeloma, mantle cell lymphoma, diffuse large B-cell lymphoma and other Non-Hodgkin lymphoma cell lines in vitro. In vivo, these ADCs significantly reduced tumor growth in ANBL-6, CAG and ARP-1 multiple myeloma models and WSU-DLCL2, OCI-Ly10, SU-DHL-6 lymphoma models.
About Sutro Biopharma
Sutro Biopharma Inc. located in South San Francisco, develops best-in-class antibody drug conjugate (ADC) and multi-specific antibody-based therapeutics for cancer therapy, including immuno-oncology therapies. Sutro’s discovery and development efforts are driven by its proprietary Xpress CF™ and Xpress CF+™ platforms, a biochemical synthesis system that enables rapid and systematic evaluation of protein structure-activity relationships, as well as rapid and predictable scalability for manufacturing in Sutro’s cGMP facility. In addition to developing its own drug candidate pipeline, which is focused on mono- and bi-specific ADCs, Sutro is collaborating with select pharmaceutical and biotech companies to discover and develop novel therapeutics.
SOURCE Sutro Biopharma Inc.
Juno Therapeutics is still mulling next steps for its lead product, an experimental cancer immunotherapy now stuck in limbo because five of 68 adult leukemia patients in its current study, a clinical…
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Two years ago at the American Society of Hematology conference, excitement, not blood, was running in the streets of San Francisco. The cancer immunotherapy known as CAR-T was the star of the show,…
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