News Article | June 15, 2017
NORWOOD, MA--(Marketwired - June 15, 2017) - Corbus Pharmaceuticals Holdings, Inc. ( : CRBP) ("Corbus" or the "Company"), a clinical stage drug development company targeting rare, chronic, serious inflammatory and fibrotic diseases, announced today that safety and efficacy data from its previously completed Phase 2 clinical study of anabasum (formerly known as JBT-101) for the treatment of diffuse cutaneous systemic sclerosis was presented earlier today at the European League Against Rheumatism ("EULAR") Annual Meeting in Madrid, Spain. The presentation included a review of the Phase 2 topline data previously announced, additional data from the study regarding Patient-Reported Outcomes Measurement Information System (PROMIS)-29, and additional analysis of the previously-reported CRISS domains and transcriptome data. The abstract titled, "A Phase 2 study safety and efficacy of anabasum (JBT-101) in systemic sclerosis," was presented by Robert Spiera, M.D., Director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery, Weill Cornell Medical College in New York City, and Principle Investigator of Corbus' Phase 2 systemic sclerosis clinical study. To view the presentation, please click here. Anabasum was granted Orphan Drug Designation and Fast Track status for the treatment of systemic sclerosis from the FDA in 2015 and Orphan Designation from the EMA in January 2017. Corbus also has an ongoing 12-month, open-label extension to its Phase 2 clinical study of anabasum for systemic sclerosis and expects to report data from this study in the fourth quarter of 2017. Following an end-of-Phase 2 meeting with the FDA, Corbus announced its plans to commence a Phase 3 study of anabasum for the treatment of systemic sclerosis in the fourth quarter of 2017. The international Phase 3 trial will be a double-blind, randomized, placebo-controlled study conducted in approximately 270 adults with systemic sclerosis. Subjects will be randomized to receive anabasum 20 mg twice per day, anabasum 5 mg twice per day, or placebo twice per day. Corbus expects to complete enrollment of this 52-week study in 2018 and expects to conclude the study by the end of 2019. Systemic sclerosis is a chronic, systemic autoimmune rheumatic disease with an unclear etiology. Systemic sclerosis affects approximately 90,000 people in the United States and Europe, with disease onset typically in mid-life. About 80 percent of systemic sclerosis patients are women. The disease process in systemic sclerosis includes activation of the immune system, with damage to small blood vessels and fibrosis of the skin on internal organs, including lungs, heart, kidneys, gastrointestinal tract and musculoskeletal system. Chronic disease burden, morbidity and mortality are significant. Cardiopulmonary disease is the major cause of death in systemic sclerosis. Immunosuppressive medications such as oral corticosteroids, methotrexate, cyclophosphamide, and mycophenolate mofetil are used to treat patients with more severe signs and symptoms of disease. Currently, there are no FDA-approved treatments specifically indicated for the treatment of systemic sclerosis, other than pulmonary artery hypertension secondary to connective tissue diseases such as systemic sclerosis. Anabasum is a novel synthetic oral endocannabinoid-mimetic drug that preferentially binds to the CB2 receptor expressed on activated immune cells and fibroblasts. CB2 activation triggers endogenous pathways that resolve inflammation and halt fibrosis. Preclinical and human clinical studies have shown anabasum to have a favorable safety, tolerability and pharmacokinetic profile. It has also demonstrated promising potency in preclinical models of inflammation and fibrosis. Anabasum is designed to trigger the production of "Specialized Pro-resolving Lipid Mediators" that activate an endogenous cascade responsible for the resolution of inflammation and fibrosis, while reducing production of multiple inflammatory mediators. Anabasum also is designed to have direct effects on fibroblasts to halt tissue scarring. In effect, anabasum triggers endogenous pathways to turn "off" chronic inflammation and fibrotic processes, without causing immunosuppression. Corbus Pharmaceuticals Holdings, Inc. is a Phase 3 clinical stage pharmaceutical company focused on the development and commercialization of novel therapeutics to treat rare, chronic, and serious inflammatory and fibrotic diseases. The Company's lead product candidate, anabasum, is a novel synthetic oral endocannabinoid-mimetic drug designed to resolve chronic inflammation and fibrotic processes. Anabasum has demonstrated positive results in two Phase 2 studies, one in diffuse cutaneous systemic sclerosis and one in cystic fibrosis. Additionally, anabasum is being evaluated in a 12-month open-label extension study in diffuse cutaneous systemic sclerosis, a Phase 2 study in skin-predominant dermatomyositis with a 12-month open-label extension, and soon in another Phase 2 study in systemic lupus erythematosus. Corbus plans to commence a Phase 3 study to support a New Drug Application (NDA) of anabasum for the treatment of systemic sclerosis in the fourth quarter of 2017. The Company is also planning to initiate a larger and longer Phase 2b study of anabasum for the treatment of cystic fibrosis in the fourth quarter of 2017. For more information, please visit www.CorbusPharma.com and connect with the Company on Twitter, LinkedIn, Google+ and Facebook. This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company's product development, clinical trials, clinical and regulatory timelines, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statement that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions. These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential," "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
News Article | June 14, 2017
BOUDRY, Switzerland--(BUSINESS WIRE)--Celgene International Sàrl, a wholly owned subsidiary of Celgene Corporation (NASDAQ:CELG), today announced results from the phase 2a SLE-001 trial evaluating CC-220, the Company's investigational, oral immunomodulatory compound, at the Annual European Congress of Rheumatology (EULAR) 2017 in Madrid. A trend toward greater improvement with CC-220 treatment compared with placebo in multiple measures of disease activity, as measured by standard scores employed in clinical trials, was observed in patients with systemic lupus erythematosus (SLE), commonly known as lupus. “While the outlook for patients with lupus has improved over the last 75 years, treatment options remain limited,” said Dr. Richard Furie, chief of Rheumatology at Northwell Health in New York. “New treatment options are greatly needed for people who are dealing with this often disabling autoimmune condition.” The SLE-001 study randomized 42 patients who were diagnosed with lupus at least six months before and had a baseline SELENA-SLEDAI score greater than or equal to four. Participants were randomized to one of four escalating doses of CC-220 (CC-220 0.3 mg every other day, 0.3 mg once daily, 0.3 mg alternating with 0.6 mg once daily and 0.6 mg once daily) or placebo for 12 weeks, followed by 12 weeks of observational follow-up or long-term extension. The study evaluated safety, tolerability and pharmacokinetics. Efficacy endpoints, including changes in Cutaneous Lupus Area and Severity Activity Index (CLASI) and SELENA-SLEDAI score, were exploratory. The most common adverse events (AEs) were nausea, diarrhea and maculopapular rash. Serious AEs were reported in two patients in the two highest CC-220 doses combined (pneumonia in both cases) and in two patients in the placebo group. Five patients in the two highest CC-220 dose groups and one patient in the placebo group discontinued due to AEs. No opportunistic infections or other systemic infections were reported in any CC-220 dose groups. At day 85, reductions in skin-specific disease activity, as measured by CLASI, ranged from -4.3 to -7.8 in the CC-220 treatment groups, while a CLASI score increase of 0.4 was seen in the placebo group. Mean reductions in CLASI exceeded the minimal clinically important difference of -4.0 in the CC-220 groups. Additionally, more patients receiving CC-220 had at least a 4-point reduction in SELENA-SLEDAI score—an index used to assess lupus disease activity across 24 different disease descriptors (between 22.2 percent and 50.0 percent for CC-220 vs. 12.5 percent for placebo). A trend toward greater improvement in tender joint count and swollen joint count was seen in the CC-220 treatment groups compared with the placebo group at day 85. A trend toward improvement in the Physician’s Global Assessment score was also seen at day 85 in the CC-220 groups (ranging from -0.5 to -0.9) compared with the placebo group (0.0). All data are as observed. The low number of study patients and some variability in baseline disease characteristics across treatment groups limit the interpretability of a dose response. “Celgene is committed to addressing immunological diseases with serious unmet needs and investigating compounds that we believe could have the potential to improve the lives of patients. We’re excited by the possibility that CC-220 may offer a novel mechanism to address lupus, a complex disease that has few effective treatment options,” said Terrie Curran, President, Celgene Inflammation & Immunology. “Our work with CC-220 will also help to diversify and deepen our Inflammation and Immunology franchise as we continue to advance CC-220 in the clinic.” CC-220 is not approved for use in any indication in any country. CC-220 is a novel, oral immunomodulatory compound that binds to and modulates cereblon, a component of the E3 ubiquitin ligase complex. CC-220 reduces levels of the transcription factors Ikaros and Aiolos, which are associated with an increased risk of lupus. CC-220 is currently being studied in a phase 2 dose-finding study for lupus. It is also being studied in multiple myeloma. Systemic lupus erythematosus (SLE), commonly known as lupus, is an autoimmune disease in which the immune system creates antibodies that attack the body’s healthy cells and tissues, including joints, skin, kidneys, heart, lungs, blood vessels and brain. Lupus affects five million people, mostly women, worldwide. Symptoms of lupus may vary, but the most common include fatigue, pain or swelling in joints, muscle pain, skin rashes, hair loss, seizures, sun sensitivity, ulcers and fever as well as lung, kidney and heart problems. The disease may have periods without symptoms (known as remission) alternating with periods of disease flares. There is no cure for lupus, but medical interventions and lifestyle changes can help control it. Celgene International Sàrl, located in Boudry, Switzerland, is a wholly-owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube. This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans,” “will,” “outlook” and similar expressions. Forward-looking statements are based on management’s current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and our other reports filed with the U.S. Securities and Exchange Commission. References 1. National Institutes of Health. What is Lupus? Retrieved May 24, 2017, from https://www.niams.nih.gov/health_info/lupus/lupus_ff.pdf 2. Centers for Disease Control and Prevention. Lupus Basic Fact Sheet. (2017, March 21). Retrieved May 24, 2017, from https://www.cdc.gov/lupus/basics/index.html 3. Center for Integrated Healthcare. Lupus Information Sheet. (2013, July). Retrieved May 24, 2017, from https://www.mirecc.va.gov/cih-visn2/Documents/Provider_Education_Handouts/Lupus_Information_Sheet_for_BHPs_Version_3.pdf
Puechal X.,systemIC |
Puechal X.,University of Paris Descartes
Annals of the Rheumatic Diseases | Year: 2013
Whipple's disease is a chronic, systemic infection caused by Tropheryma whipplei. Gene amplification, isolation and DNA sequencing of T whipplei have extended our knowledge of this pathogen, which is now recognised as a ubiquitous commensal bacterium. The spectrum of signs associated with T whipplei has now been extended beyond the classic form, which affects middle-aged men, and begins with recurrent arthritis followed several years later by digestive problems associated with other diverse clinical signs. Children may present an acute primary infection, but only a small number of people with a genetic predisposition subsequently develop authentic Whipple's disease. This bacterium may also cause localised chronic infections with no intestinal symptoms: endocarditis, central nervous system involvement, arthritis, uveitis and spondylodiscitis. An impaired TH1 immune response is seen. T whipplei replication in vitro is dependent on interleukin 16 and is accompanied by the apoptosis of host cells, facilitating dissemination of the bacterium. In patients with arthritis, PCR with samples of joint fluid, saliva and stools has become the preferred examination for diagnosis. Immunohistochemical staining is also widely used for diagnosis. Treatment is based on recent microbiological data, but an immune reconstitution syndrome and recurrence remain possible. The future development of serological tests for diagnosis and the generalisation of antigen detection by immunohistochemistry should make it possible to obtain a diagnosis earlier and thus to decrease the morbidity, and perhaps also the mortality, associated with this curable disease which may, nonetheless, be fatal if diagnosed late or in an extensive systemic form.
Alijotas-Reig J.,systemIC |
Alijotas-Reig J.,Autonomous University of Barcelona
Lupus | Year: 2013
Objective: To date, there are no reliable data regarding the actual treatment received by women with refractory obstetric antiphospholipid syndrome (OAPS). The aim of this study was to assess current clinical evidence and new trends in the treatment of refractory OAPS. Methods: A non-systematic but comprehensive literature search using relevant keywords was made to identify relevant articles published in English from different computerized databases: PubMed (Medline), Google Scholar electronic database search and The Cochrane Library, from January 2000 to March 2012. Studies on the treatment of poor obstetric outcomes in women with OAPS were included. Prospective randomized clinical trials, cohort studies, reviews, systematic reviews and meta-analysis were retrieved. Results: A total of 130 articles were finally selected for this review, including 17 randomized clinical trials and four meta-analyses. The majority of articles were non-randomized original papers and basic and clinical reviews. Conclusion: Up to 20% of women with OAPS do not receive the currently recommended therapeutic regimen. Unfortunately, well-designed studies regarding the usefulness of new drugs in refractory OAPS are scarce. Hydroxychloroquine and low-dose prednisolone appear to be useful when added to standard therapy. Current data do not support the use of intravenous immunoglobulins in this field. The role played by double antiaggregant therapy, fondaparinux, vitamin D, pentoxifylline and TNF-targeted therapies should be tested in well-designed studies. © The Author(s), 2012.
Ferreira I.,systemIC |
Isenberg D.,University College London
Annals of the Rheumatic Diseases | Year: 2014
Patients with autoimmune rheumatic diseases are more susceptible to infectious complications during the course of their disease. The introduction of biologics has been a major achievement in treating these diseases, but an increased risk of infection associated with these therapies has become evident. Some infections can be prevented by vaccination and it is clearly worthwhile considering which immunisations would be sensible and practicable for these patients. To date no formal specific recommendations for patients on biologics have been published. A search was made of Medline (via PubMed) from 1970 to January 2014 to provide results. This review aims to provide a systematic analysis of the data about vaccines and biologics and considers recommendations for vaccination in adult patients with autoimmune rheumatic diseases treated with biologics.
Lupus | Year: 2012
The LupusQoL© questionnaire is a disease-specific health related quality of life (HRQOL) instrument for adults with systemic lupus erythematosus (SLE). The Short Form-36 (SF-36) is a generic instrument that captures the physical, psychological, and social impact. We conducted a descriptive study of women aged ≥ 18 years attending our Lupus Clinic. HRQOL was assessed by applying the LupusQoL© and SF-36. Lupus activity was measured using the Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and chronic damage using the Systemic Lupus Collaborative Clinics Damage Index (SDI). Data were analyzed using descriptive statistics, the chi-square test and Pearson's product moment correlation coefficient. A total of 127 patients were included with a mean age of 40.5 ± 12.6 years. The mean disease duration was 8.2 ± 5.6 years, the mean disease activity score was 2.4 ± 3.0, and the mean SDI score 0.77 ± 1.06. The mean SF-36 score was 58.1 ± 21.1 and the mean LupusQoL© score was 69 ± 22.7. The correlation between global scores of the SF-36 and LupusQoL© was rho = 0.73 (p < 0.001). The correlation between lupus disease activity and the SF-36 and the LupusQoL© was -0.26 (p = 0.003) and -0.25 (p = 0.004), respectively. The correlation between the SDI and the SF-36 and the LupusQoL© was -0.28 (p = 0.001) and -0.38 (p < 0.0001), respectively. In conclusions: both LupusQoL© and SF-36 were useful instruments in assessing HRQOL in Mexican lupus female patients. The usefulness of the LupusQoL© should be evaluated in lupus patients with moderate to severe disease activity.
Vascular health and risk management | Year: 2013
The aim of this study was to assess the effects of continuous positive airway pressure (CPAP) on arterial stiffness, central blood pressure, and reflected pulse wave characteristics in patients with severe obstructive sleep apnea (OSA) and stage 2-3 arterial hypertension. Forty-four patients with hypertension and severe OSA (apnea/hypopnea index > 30) received stepped dose titration of antihypertensive treatment, consisting of valsartan 160 mg + amlodipine 5-10 mg + hydrochlorothiazide 25 mg. CPAP therapy was added after 3 weeks of continuous antihypertensive treatment with BP < 140/90 mmHg or after adjusting triple treatment in patients with resistant arterial hypertension. The patients were randomized to effective CPAP (4-15 mm H2O) or placebo CPAP (pressure 4 mm H2O) for three weeks, then crossed over to the alternative treatment in a single-blind manner. Office blood pressure (BP), ambulatory BP monitoring, ambulatory arterial stiffness index (AASI), aortic BP, carotid-femoral pulse wave velocity (cfPWV), and systolic wave augmentation index were measured using a Sphygmocor® device at baseline, after antihypertensive treatment, placebo CPAP, and effective CPAP. Baseline cfPWV was above the normal range in 94% of patients. After reaching target BP, the cfPWV decreased by 1.9 ± 1.0 msec (P = 0.007). Effective CPAP achieved a further cfPWV reduction of 0.7 msec (P = 0.03). Increased arterial stiffness (pulse wave velocity > 12 msec) persisted in 35% of patients on antihypertensive treatment and effective CPAP, in 56% of patients on antihypertensive treatment alone, and in 53% of patients on placebo CPAP. Only the combination of antihypertensive treatment with effective CPAP achieved a significant reduction in augmentation index and AASI, along with a further reduction in aortic and brachial BP. Effective CPAP for 3 weeks resulted in a significant additional decrease in office BP, ambulatory BP monitoring, central BP, and augmentation index, together with an improvement in arterial stiffness parameters, ie, cfPWV and AASI, in a group of hypertensive patients with OSA.
Kahlenberg J.M.,University of Michigan |
Current Opinion in Rheumatology | Year: 2014
PURPOSE OF REVIEW: The role of innate immunity in systemic lupus erythematosus (SLE) has been a rapidly expanding area of research over the last decade. Included in this rubric is the concept that activation of the inflammasome, a molecular complex that activates caspase-1 and in turn the cytokines IL-1β and IL-18, is important in lupus pathogenesis. This review will summarize the recent discoveries exploring the role of the inflammasome machinery in SLE. RECENT FINDINGS: Immune complexes can activate the NLRP3 inflammasome, and SLE-derived macrophages are hyper-responsive to innate immune stimuli, leading to enhanced activation of the inflammasome and production of inflammatory cytokines. Work in several murine models suggests an important role for the NLRP3 inflammasome in mediating lupus nephritis. Caspase-1, the central enzyme of the inflammasome, is essential for the development of type I interferon responses, autoantibody production, and nephritis in the pristane model of lupus. The absence of melanoma 2 inflammasome may have protective and pathogenic roles in SLE. SUMMARY: Recent evidence suggests that the inflammasome machinery is dysregulated in SLE, plays an important role in promotion of organ damage, and may mediate cross-talk between environmental triggers and the development of lupus. Further research should focus on whether inhibition of inflammasome components may serve as a viable target for therapeutic development in SLE. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Current Biology | Year: 2011
The lamprey brain has now been shown to have basal ganglia circuitry, with an output that acts tonically on midbrain and brainstem motor centers and is modulated by ascending dopaminergic input. This condition was believed to represent the tetrapod condition, but now appears to be far more ancient. © 2011 Elsevier Ltd. All rights reserved.
Acta Physiologica | Year: 2014
This review analyses whether skin temperature represents ambient temperature and serves as a feedforward signal for the thermoregulation system, or whether it is one of the body's temperatures and provides feedback. The body is covered mostly by hairy (non-glabrous) skin, which is typically insulated from the environment (with clothes in humans and with fur in non-human mammals). Thermal signals from hairy skin represent a temperature of the insulated superficial layer of the body and provide feedback to the thermoregulation system. It is explained that this feedback is auxiliary, both negative and positive, and that it reduces the system's response time and load error. Non-hairy (glabrous) skin covers specialized heat-exchange organs (e.g. the hand), which are also used to explore the environment. In thermoregulation, these organs are primarily effectors. Their main thermosensory-related role is to assess local temperatures of objects explored; these local temperatures are feedforward signals for various behaviours. Non-hairy skin also contributes to the feedback for thermoregulation, but this contribution is limited. Autonomic (physiological) thermoregulation does not use feedforward signals. Thermoregulatory behaviours use both feedback and feedforward signals. Implications of these principles to thermopharmacology, a new approach to achieving biological effects by blocking temperature signals with drugs, are discussed. © 2014 The Author.