Breaking News
October 22, 2018 - Overcoming bottlenecks in early drug discovery with the power of sound
October 22, 2018 - Scientists discover genes that contribute to ADHD development
October 22, 2018 - Incyte announces Phase 2 FIGHT-202 trial data in patients with cholangiocarcinoma
October 22, 2018 - FDA approves update to Rituxan label to include information on treatment of rare forms of vasculitis
October 22, 2018 - At-home biofeedback therapy effective in relieving difficult-to-treat constipation
October 22, 2018 - Merck presents KEYNOTE-057 trial results for patients with high-risk non-muscle invasive bladder cancer
October 22, 2018 - People with periodontal disease less likely to reach healthy blood pressure ranges
October 22, 2018 - Phase III LONSURF study shows progression-free survival in patients with refractory metastatic gastric cancer
October 22, 2018 - Primary care doctors ‘not doing enough’ to curb STDs
October 22, 2018 - Pfizer announces PALOMA-3 trial results in patients with HR+, HER2- metastatic breast cancer
October 22, 2018 - ImmunoGen announces study results of platinum-resistant ovarian cancer therapy at ESMO 2018 Congress
October 22, 2018 - Study findings could set new standard of care for advanced anal cancer
October 22, 2018 - Erlotinib improves progression-free survival in EGFR mutated NSCLC
October 22, 2018 - Pain, insomnia, and depression often drive osteoarthritis patients to seek medical care
October 22, 2018 - The International Society of Refractive Surgery honors Vivior Chairman with Casebeer Award
October 22, 2018 - Multi-strain probiotic helps reduce chemotherapy-induced diarrhea in cancer patients
October 22, 2018 - Study shows potential of avelumab plus axitinib as new treatment option for patients with advanced RCC
October 22, 2018 - Vertex gets European CHMP positive opinion for KALYDECO to treat patients with cystic fibrosis
October 22, 2018 - Phase III trial reports positive results with HDAC inhibitor in advanced breast cancer patients
October 22, 2018 - Prostate radiotherapy improves survival in men with low burden of metastatic disease
October 22, 2018 - Free phone app helps low-income obese patients to lose weight
October 22, 2018 - Immunotherapy with nivolumab and ipilimumab may improve survival in patients with MSI-high metastatic colorectal cancers
October 22, 2018 - FOTIVDA expected to be included in new ESMO guidelines for advanced renal cell carcinoma
October 22, 2018 - Compression Collar May Protect Brain of Female Soccer Players
October 22, 2018 - Technique visualizes neuron communication
October 22, 2018 - Advancement in medical imaging methods for health care
October 22, 2018 - Takeda presents vedolizumab phase 3 VISIBLE 1 trial results for treatment of moderately to severely active ulcerative colitis
October 22, 2018 - Immunotherapy increases survival in some patients with metastatic triple negative breast cancer
October 22, 2018 - Exelixis presents CABOSUN and METEOR trial results in patients with advanced renal cell carcinoma
October 22, 2018 - LYNPARZA Phase III SOLO-1 results show improved outcome for patients with advanced BRCA-mutated ovarian cancer
October 22, 2018 - Brainlab unveils ExacTrac Dynamic at ASTRO meeting in San Antonio, Texas
October 22, 2018 - Not exercising is worse than smoking, diabetes or heart disease finds study
October 22, 2018 - Shorter course of trastuzumab could be an option for women with HER2+ early breast cancer
October 22, 2018 - Map of Mouse Hippocampus Could Be Weapon Against Alzheimer’s
October 22, 2018 - Psychotropic polypharmacy is common in Alzheimer’s disease
October 22, 2018 - Texas A&M and UTA establish Texas Genomics Core Alliance
October 22, 2018 - Analyzing mouse’s potential as animal model of decision-making
October 22, 2018 - Radiotherapy can prolong survival in prostate cancer
October 22, 2018 - A genetic mutation involved in relapse
October 21, 2018 - Report reveals growing impact of cannabis on young people
October 21, 2018 - NSF awards $5 million grant to help scientists magnify societal impact of research
October 21, 2018 - Fertility Rates Down for Each Urbanization Level 2007 to 2017
October 21, 2018 - Genetically engineered 3-D human muscle transplant in a murine model
October 21, 2018 - Moms’ tight work schedules may affect their children’s sleep
October 21, 2018 - AHA: No Direct Link Between Preeclampsia and Cognitive Impairment, Study Finds
October 21, 2018 - Weight loss success linked with active self-control regions of the brain
October 21, 2018 - Scripps researchers successfully test potential new smoking-cessation treatment in rodents
October 21, 2018 - More accurate and less stressful way to measure a baby’s heartbeat
October 21, 2018 - Researchers show better cardiorespiratory fitness leads to longer life
October 21, 2018 - Healthy candies for diabetic patients
October 21, 2018 - Environment impact of microplastics remains unclear
October 21, 2018 - Antibiotics for appendicitis? Surgery often not needed
October 21, 2018 - AHA and AMA recognize more than 800 medical practices, health systems for blood pressure control
October 21, 2018 - Scientists obtain clearest ever image of Ebola virus protein
October 21, 2018 - Study reveals connection between two proteins known to be hyperactive in cancer
October 21, 2018 - Gabapentin Beats Pregabalin for Chronic Sciatica
October 21, 2018 - Cosmetic surgeons offering incomplete information for breast augmentation customers
October 21, 2018 - Chronic sleep disruption in early adult life accelerates AD-related tau pathology
October 21, 2018 - Take 10 for Mindfulness – Drugs.com MedNews
October 21, 2018 - Length of breathing disruption in OSA may be better predictor of mortality risk
October 21, 2018 - ApoE4 gene linked with chronic inflammation increases risk for Alzheimer’s disease
October 21, 2018 - Mother-daughter conflict associated with suicide risk in abused adolescent girls
October 21, 2018 - Scientists molding bacteria into unnatural shapes
October 21, 2018 - High diet quality associated with lower risk of death in colorectal cancer patients
October 21, 2018 - Discharged mental health patients ‘at greater risk of dying’
October 21, 2018 - Research provides insight into neurobiology of aggression and bullying
October 21, 2018 - As billions in tax dollars flow to private Medicaid plans, Who’s minding the store?
October 21, 2018 - Neuroscientists identify brain region that appears to be related to food preference decisions
October 21, 2018 - Deaths related to air pollution in the U.S. decreased by 47% between 1990 and 2010
October 21, 2018 - Study shows correlation between spatial memory and the sense of smell
October 21, 2018 - Increased cardiorespiratory fitness associated with reduced long-term mortality
October 21, 2018 - IU researchers receive $1.55 million from NIH to improve chronic-disease management
October 21, 2018 - Income and wealth affect the mental health of Australians, study shows
October 21, 2018 - Patients with hypertension and psoriasis more often require cardiovascular interventions
October 20, 2018 - Leading hip-hop videos depict use of tobacco and marijuana products, study finds
October 20, 2018 - Dose Range of IV Ketamine for Adjunct Tx of Depression Tested
October 20, 2018 - Infants can distinguish between leaders and bullies, study finds
October 20, 2018 - Mad Cow disease found on Aberdeenshire farm
October 20, 2018 - Study identifies factors associated with prescription opioid misuse among students
October 20, 2018 - Scientists uncover key regulator of mTORC1 in cancer growth
Novartis Drug Crizanlizumab Shown to Prolong Time to Patients’ First Sickle Cell Pain Crisis in Subgroup Analysis of SUSTAIN Study

Novartis Drug Crizanlizumab Shown to Prolong Time to Patients’ First Sickle Cell Pain Crisis in Subgroup Analysis of SUSTAIN Study

image_pdfDownload PDFimage_print

Basel, December 11, 2017 – Results from a post hoc subgroup analysis of the Phase II SUSTAIN study show that crizanlizumab, an investigational humanized anti-P-selectin monoclonal antibody, delayed the time to first sickle cell pain crisis (SCPC) in patients vs. placebo in key subgroups of adult patients with sickle cell disease[1]. Findings were featured during an oral session at the 59th American Society of Hematology (ASH) Annual Meeting (Abstract #613; Monday, December 11, 10:30 AM ET).

Acute sickle cell pain crises, also referred to as vaso-occlusive crises, are a common painful complication of the disease and the main reason that patients seek medical care in hospitals.[2]

Currently, treatment options are limited. The data from a subgroup analysis of the Phase II SUSTAIN study showed that crizanlizumab, at 5.0 mg/kg per month increased the time to SCPC in patients on treatment, including those in high-risk subpopulations and with hydroxyurea use[1].

“Pain is the primary cause of suffering in sickle cell disease,” said Julie Kanter, M.D., Division of Pediatrics, Medical University of South Carolina, a study investigator. “What this new analysis of the SUSTAIN data suggests is that once patients start crizanlizumab, they are likely to have a longer time before experiencing another pain crisis. These findings are consistent regardless of the severity of disease, genotype, or the use of background therapy. That is a potentially promising new development for patients. Fewer pain crises mean less organ damage long term.”

The analysis looked at the following subgroups of patients with sickle cell disease:

  • Patients with 2-4 or 5-10 SCPC events in the year before the study
  • Patients with the HbSS genotype, and non-HbSS genotypes
  • Patients who were or were not taking hydroxyurea

In all of these subpopulations, crizanlizumab at 5.0 mg/kg per month increased the estimated median time to first SCPC vs. placebo by approximately two-fold or more.

In patients taking crizanlizumab who experienced 2-4 SCPCs in the prior year, time to first on-treatment pain crisis was 4.8 vs 1.6 months with placebo (HR 0.53 with 95% CI [0.31, 0.90]). For patients with 5-10 SCPCs in the prior year, time to first on-treatment pain crisis was 2.4 vs 1.0 months (HR 0.47 with a 95% CI [0.25, 0.89]).

In patients with the HbSS genotype, there was a 3.7-fold increase in estimated median time to first SCPC in those taking crizanlizumab vs. placebo (4.1 vs 1.1 months; HR 0.50 with 95% CI [0.31, 0.80]). In patients taking hydroxyurea, the time to first on-study SCPC was longer with crizanlizumab vs placebo (2.4 vs 1.2 months; HR 0.58 with 95% CI [0.35, 0.96]), suggesting its potential as an additive therapy[1].

“This analysis from SUSTAIN is another important step to bringing what we hope will be a new disease-modifying therapy to patients with sickle cell disease,” said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. “The results are consistent among different groups of patients, which gives us even more confidence in our development program for this promising medicine.”

About the Subgroup Analysis and the SUSTAIN trial

The heterogeneity in severity of sickle cell disease and various other factors make it important to understand differences in response of various subgroups of patients in order to increase understanding of crizanlizumab and the role of P-selectin in SCD. This post hoc analysis evaluated the time to first SCPC among subgroups of the SUSTAIN study population – those who had 2-4 or 5-10 SCPCs within the prior year; patients with HbSS or non-HbSS genotypes; and patients with or without concomitant treatment with hydroxyurea. The goal was to further assess the efficacy of crizanlizumab at 5.0 mg/kg per month vs placebo, and identify differences in treatment response among those subgroups[1].

The SUSTAIN trial was a multicenter, multinational, randomized, placebo-controlled, double-blind, 12-month study to assess safety and efficacy of the anti-P-selectin antibody crizanlizumab with or without concomitant use of hydroxyurea therapy in sickle cell disease patients with sickle cell-related pain crises. Results, which were published in The New England Journal of Medicine, showed that crizanlizumab reduced the median annual rate of SCPCs by 45% compared to placebo (1.6 vs 3.0, p=0.01) in patients with or without hydroxyurea therapy.[3] These data will help support discussions with regulatory agencies, with filing anticipated in the U.S. by the end of 2018.

Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. There were no apparent increases in infections with crizanlizumab treatment.[3]

About crizanlizumab (SEG101)

Crizanlizumab (SEG101) is an investigational humanized anti-P-selectin monoclonal antibody that binds a molecule called P-selectin on the surface of endothelial cells and platelets in the blood vessels, causing a blockade of P-selectin[3],[4]. P-selectin is a driver of the vaso-occlusive process[3],[5]. Vaso-occlusive crises, also known as SCPCs, occur episodically when sickle-shaped red blood cells block blood flow through blood vessels[6]. The therapeutic blockade of P-selectin can prevent painful vaso-occlusion in small blood vessels and maintain blood flow[3],[6].

Disclaimer

This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; general economic and industry conditions, including the effects of the persistently weak economic and financial environment in many countries; safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 121,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.

References

[1] Kanter J, Kutlar A, Liles D, et al. Crizanlizumab 5.0 mg/kg increased the time to first on-treatment sickle cell pain crisis: A subgroup analysis of the Phase II SUSTAIN study. Abstract #613. 2017 59th American Society of Hematology (ASH) Annual Meeting, Atlanta, GA.
[2] Puri L, Nottage K et al. State of the Art Management of Acute Vaso-occlusive Pain in Sickle Cell Disease Pediatr Drugs, epub Aug 2017 DOI 10.1007/s40272-017-0263-z
[3] Ataga KI, Kutlar A, Kanter J et al. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb 2;376(5):429-439.
[4] Miller ST, Kim HY, et al. for Sickle Cell Disease Clinical Research Network (SCDCRN). Inpatient management of sickle cell pain: A ‘snapshot’ of current practice. Am J Hematol. 2012 Mar;87(3):333-336.
[5] Novartis Pharmaceuticals Corporation. Data on file. 2016.
[6] Quinn CT. Anti-adhesive therapy for sickle cell disease. The Hematologist. 2014; 11(6):15.

Source: Novartis

Posted: December 2017

Tagged with:

About author

Related Articles