Swedish Orphan Biovitrum AB (publ) (Sobi™) has been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for the company’s development candidate SOBI003, a chemically modified human recombinant sulfamidase for the treatment of mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A, a rare metabolic disorder.“We are very pleased with the orphan drug designation from the FDA for SOBI003. MPS IIIA is a severe and debilitating disease, and this development program is an important part of our mission of being pioneers in rare diseases. We are currently in the late pre-clinical phase and expect to initiate the first clinical trial with SOBI003 in 2018,” said Milan Zdravkovic, Chief Medical Officer and Head of Research and Development at Sobi.Onset of Mucopolysaccharidosis type IIIA is in early childhood, and the disease is characterised by severe and progressive developmental delay, motor retardation and eventually dementia. One in 100,000 children are born with the inherited condition and very few patients survive into adulthood. There is presently no treatment for MPS IIIA. SOBI003 was granted orphan designation by the European Commission for MPS IIIA in October 2016.---About Orphan Drug Designation The Orphan Drug Designation programme provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug. The granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. Orphan designation qualifies the sponsor of the drug for various development incentives of the Orphan Drug Act, such as a 50 per cent tax credit on the cost of clinical trials undertaken in the US and a seven-year period of marketing exclusivity following market approval. [i]About mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) MPS IIIA or Sanfilippo A syndrome is a progressive, life-threatening and rare inherited metabolic disorder affecting children already from a young age. MPS IIIA belongs to a group of diseases called Lysosomal Storage Disorders (LSDs). In MPS IIIA, the body is unable to break down long chains of sugar molecules called heparan sulfate, resulting in the accumulation of heparan sulfate in lysosomes. MPS IIIA mainly affects the central nervous system where it causes severe progressive degeneration. [ii]Approximately 1,000-2,000 persons are estimated to live with MPS IIIA in the E.U. and U.S. The disease is usually identified at around four years of age and the life-span of an affected child does not usually extend beyond the third decade of life. There is no treatment for MPS IIIA to date.About SOBI003 SOBI003 is a chemically modified variant of a recombinant human sulfamidase product candidate, using Sobi’s proprietary glycan modification technology, intended as an enzyme replacement therapy to reduce heparan sulfate storage materials in affected cells. SOBI003 is taken up by cells and transported into the lysosomal compartment where heparan sulfate is degraded. The modification of the molecule results in an extended half-life.About Sobi™ Sobi is an international specialty healthcare company dedicated to rare diseases. Sobi’s mission is to develop and deliver innovative therapies and services to improve the lives of patients. The product portfolio is primarily focused on Haemophilia, Inflammation and Genetic diseases. Sobi also markets a portfolio of specialty and rare disease products across Europe, the Middle East, North Africa and Russia for partner companies. Sobi is a pioneer in biotechnology with world-class capabilities in protein biochemistry and biologics manufacturing. In 2016, Sobi had total revenues of SEK 5.2 billion (USD 608 M) and about 760 employees. The share (STO: SOBI) is listed on Nasdaq Stockholm. More information is available at www.sobi.com .For more information please contactMedia relations Investor relations Linda Holmström, Senior Communications Manager Jörgen Winroth, Vice President, Head of Investor Relations +46 708 734 095 +1 347 224 0819, +1 212 579 0506 email@example.com firstname.lastname@example.org
Isofol Medical AB (publ) announced today that the first six patients were enrolled and dosed in the ISO-FF-001 study. The study, which is part of the regulatory documentation required for an oncology drug to be granted approval, investigates possible effects of Modufolin on heart rhythm (ECG). The ISO-FF-001 is performed under an IND at the CTC (clinical Trial Consultants) study facility in Uppsala, Sweden. The study is planned to be finalized in August 2017.Isofol Medical AB (publ), a clinical staged oncology company, announced today that the first six patients were enrolled and dosed in the ISO-FF-001 study. The study is performed under Isofol's IND (investigational new drug) for colorectal cancer which was cleared by the FDA (Food and Drug Administration) in January 2017 after a comprehensive review of Isofol's collected preclinical and clinical data and future development plan within colorectal cancer. ISO-FF-001 is a, randomized, double-blind, single-center, placebo-controlled Phase I study evaluating ECG effects (i.e. QTc prolongation) , safety, tolerability and pharmacokinetics of single ascending doses (200, 350 and 500 mg/m2) of Modufolin® in healthy male volunteers. At least 33 eligible and consenting subjects will be included in 3 cohorts, 11 subjects in each cohort. Within each cohort, subjects will be randomized to receive either placebo (3 subjects) or Modufolin® (8 subjects). There will be an interval between each dose level to allow time for safety data to be analysed and evaluated.There have been no indications, neither from pre-clinical development nor from ongoing clinical trials, that Modufolin affects heart rhythm (ECG) but a study of this type is an important regulatory requirement for clinical development and is part of Isofol’s development plan. The ISO-FF-001 study will also allow Isofol to collect pharmacokinetic and pharmacodynamics data on Modufolin®, given solely, in healthy volunteers.“ Isofol now further advances the clinical development plan for Modufolin®. FDA's clearance to conduct the study under an IND, is a confirmation of the high quality of Isofol’s documentation of Modufolin® and another puzzle in Isofol’s efforts to launch the planned registration study with Modufolin®, ISO-CC-007, at the turn of the year 2017/2018 ”, says Anders Rabbe, CEO of Isofol Medical.The ISO-FF-001 study is Isofol's first IND study (a clinical clearance given by the American FDA) is conducted at the CTC (clinical Trial Consultants) study facility in Uppsala. The study is also approved by the Swedish Medical Products Agency (Läkemedelsverket) and the Regional Ethical Review Board in Uppsala. The study is expected to be completed in early of August 2017For more information, please contact:Anders Rabbe, CEO, Isofol Medical ABEmail: email@example.comPhone: +46 (0)707 646 500About Modufolin®Modufolin® (active ingredient [6R]-5,10-methylenetetrahydrofolate), is a novel folate-based compound developed to increase the efficacy and reduce the side effects of antimetabolites used in cancer treatment. It is the key active metabolite of the widely used folate-based drugs leucovorin and levoleucovorin. As Modufolin® does not require metabolic activation to exert it’s effect, Modufolin® is suitable for all patients irrespective of their capacity to activate folates. Modufolin® is currently being evaluated in two clinical Phase II studies.About Isofol Medical ABIsofol Medical AB is a clinical stage oncology company developing Modufolin® as a first-line treatment of metastatic colorectal cancer and as a rescue drug after high-dose methotrexate treatment in osteosarcoma. Through a worldwide exclusive license agreement, Isofol Medical holds the rights to commercialise Modufolin® with access to the unique patented production process and the production capabilities of Merck KGaA, Darmstadt, Germany. Isofol Medical AB is traded on the NASDAQ First North Premier. Certified Adviser is FNCA Sweden AB
Merck Awards €1.25 Million to Research Projects Through its 2017 Grant for Fertility Innovation (GFI)
• Two projects are awarded funds to advance the fertility field • Professor Lunenfeld honored with Merck Lifetime Achievement Award • The company is committed to driving innovation through evolving the product portfolio and investing in potential breakthrough researchDarmstadt, Germany, July 5, 2017 – Merck, a leading science and technology company, today announced its commitment to award €1.25 million to research projects in the field of fertility, supporting the advancement of medical science through the Grant for Fertility Innovation (GFI) in 2017. Launched as the first of the Merck Grants for Innovation in 2009, Merck’s GFI is providing encouragement for innovation and support for scientists to realize projects that could potentially lead to the next breakthrough in the fertility treatment area. This year, the GFI Award Ceremony included the announcement of the Merck Lifetime Achievement Award in Fertility Innovation.
Windtree Announces Top-Line Results from AEROSURF® Phase 2b Clinical Trial for the Treatment of Respiratory Distress Syndrome (RDS) in Premature Infants
PRNewswire/ -- Windtree Therapeutics, Inc. (OTCQB: WINT), a biotechnology company focused on developing aerosolized KL4 surfactant therapies for respiratory diseases, today announced top line results for its AEROSURF® phase 2b clinical trial evaluating aerosolized KL4 surfactant for the treatment of respiratory distress syndrome (RDS) in premature infants, 28 to 32 week gestational age, receiving nasal continuous positive airway pressure (nCPAP) for RDS. A total of 221 patients were enrolled at 48 sites in North America, Europe and Latin America.The AEROSURF phase 2b clinical trial was a multicenter, randomized, controlled study with masked treatment assignment in premature infants receiving nCPAP for RDS, and was designed to evaluate aerosolized KL4 surfactant administered to premature infants 28 to 32 week gestational age in two dose groups (25 and 50 minutes), with up to two potential repeat doses, compared to infants receiving nCPAP alone. The key objectives of this trial were to:evaluate efficacy by assessing: (i) incidence of nCPAP failure (defined as the need for intubation), (ii) time to nCPAP failure, and (iii) physiological parameters indicating the effectiveness of lung function; define the dose regimen(s) for the planned phase 3 clinical program; provide an estimation of the expected efficacy margin of AEROSURF treatment; evaluate performance and further the development of the aerosol delivery system (ADS); and further characterize the AEROSURF safety profile Based on the planned top-line results, data show that AEROSURF did not meet the primary endpoint of a reduction in nCPAP failure at 72 hours. The nCPAP failure rates for the 25 minute (n=71) and 50 minute (n=72) dose groups were comparable to nCPAP alone (n=71) (44 percent, 44 percent and 44 percent, respectively).The lack of a desired top-line treatment effect was due in large part to an unexpected rate of treatment interruptions. These treatment interruptions were primarily due to specific lots of disposable cartridge filters with a higher tendency to clog and occurred in about 23% of active enrollments, predominantly in the longer 50 minute dose group.Analysis of data of patients in the 50 minute dose group whose dose was not impacted by device-related treatment interruptions (n=45) resulted in a nCPAP failure rate of 31 percent compared to 44 percent in the control group which is a 13 percent absolute reduction or a 30 percent relative reduction in nCPAP failure compared to control. These data suggest a meaningful treatment effect in line with our targeted outcome.For AEROSURF patients who experienced nCPAP failure requiring intubation and mechanical ventilation, the time on mechanical ventilation and supplemental oxygen, as well as the level of required oxygen support, appeared to be lower compared to control patients who experienced nCPAP failure. These parameters are important risk factors for bronchopulmonary dysplasia, a chronic lung disease of the newborn and important determinants of duration of intensive care and costs of treating RDS.Overall, the safety and tolerability profile of the AEROSURF treated patients was generally comparable to the control group. All reported adverse events and serious adverse events were those that are common and expected among this fragile patient population. The incidence of adverse events and serious adverse events in the AEROSURF and control groups were generally comparable and there was no pattern observed of increasing adverse events or serious adverse events with increasing doses of AEROSURF. Furthermore, the safety and tolerability profile of the AEROSURF treated patients both with and without treatment interruptions was generally comparable to the control group."While the results did not meet the planned top-line analysis, we are very encouraged to see that, when dose is delivered as intended, the 50 minute dose exhibited a positive treatment effect with a safety profile comparable to that of nCPAP and consistent with the results we obtained in our previously completed phase 2a open-label clinical trial in similar gestational age infants," said Steve Simonson, Chief Medical Officer.Based on the results of this study, the Company plans to work with regulators and develop a phase 3 regulatory and clinical plan using its next generation ADS, the design of which has been demonstrated to mitigate the device-related treatment interruptions experienced in this phase 2b clinical trial."While analysis of data is ongoing, we believe we have achieved a number of important clinical objectives including providing evidence of a treatment effect in the higher dose and the potential to replicate desired results. We look forward to finalizing a regulatory and clinical plan to incorporate our next generation ADS, along with other learning's from this trial, as we pursue a path that will allow us to advance AEROSURF into phase 3 development," commented Craig Fraser, Chief Executive Officer.This clinical trial was supported, in part, by a .9 million Phase II award of a .6 million Fast Track Small Business Innovation Research (SBIR) grant from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under award number R44HL107000. The content of this press release is solely the responsibility of the Company and does not necessarily represent the official views of the National Institutes of Health.
Abbott Secures Health Canada License for FreeStyle® Libre System for People with Diabetes
ABBOTT PARK, IL, June 30, 2017 /CNW/ - Abbott today announced the Health Canada license of its FreeStyle® Libre Flash Glucose Monitoring System, a revolutionary new glucose sensing technology for Canadian adults with diabetes. The first-of-its-kind system eliminates the need for routine finger sticks,1 requires no finger stick calibration, and reads glucose levels through a sensor that can be worn on the back of the upper arm for up to 14 days."The first word that came to mind when I learned about FreeStyle Libre was 'freedom'," said Maria Miclea, who has been managing her Type 1 diabetes for eight years. "Freedom from the pain of routine testing and from social awkwardness. Also, peace of mind, knowing that I can quickly and easily scan my glucose levels – whenever and wherever I want – to help better manage my diabetes."HOW THE FREESTYLE LIBRE SYSTEM WORKSWith traditional glucose monitoring systems, people with diabetes often have to stick their finger a number of times throughout the day2,3 to test their glucose levels. With Abbott's FreeStyle Libre system, people now have a convenient, less painful alternative to get a glucose reading. The disposable sensor is worn on the back of the upper arm. The system measures glucose every minute in interstitial fluid through a small filament that is inserted just under the skin and held in place with a small adhesive pad. The sensor can read glucose levels through clothing,4 making testing more convenient and discreet. Each scan displays a real-time glucose result, an eight-hour historical trend and the direction the glucose is heading. The reader holds up to 90 days of data, providing a historical snapshot of glucose levels over time.FreeStyle Libre system, which is now being used by more than 300,000 people globally,5 is clinically proven to be accurate and consistent over a 14-day period, without the need for finger stick calibration."Patient glucose monitoring is an essential component of achieving effective diabetes control particularly for patients being treated with insulin," said Bernard Zinman, M.D., director of the Leadership Sinai Centre for Diabetes and senior investigator at the hospital's Samuel Lunenfeld Research Institute. "The ability for patients to easily obtain reliable and detailed self-glucose measurements, including current level and trend direction of glucose without routine finger sticks, provides the person with diabetes valuable insights into their care."OFFERING MORE VISUAL AND INSIGHTFUL GLUCOSE DATAThe data from the FreeStyle Libre system provides an Ambulatory Glucose Profile (AGP), a visual snapshot of a person's glucose fluctuations during a typical day, which can reveal hypoglycemic (low glucose levels, defined as <3.9 mmol/L6) and hyperglycemic trends intended to help facilitate better diabetes management.7,8 By automatically measuring, capturing and storing glucose level data continuously, patients and their doctors can see patterns over time and make adjustments to lifestyle, diet or treatment."At Abbott, our goal is to help people achieve their best health," said Badia Boudaiffa, general manager, Diabetes Care, Abbott, Canada. "Bringing FreeStyle Libre to the three million people living with diabetes9 across Canada is a major milestone. This technology not only transforms how people have been testing their glucose levels for decades, it also may support improved overall diabetes management."To ensure people with diabetes will have immediate access to FreeStyle Libre system once it becomes commercially available, Abbott has secured inclusion of the product in the reimbursement coverage plan of two major Canadian insurers who will notify their members upon product availability.CLINICALLY PROVEN TO BETTER MANAGE HYPOGLYCEMIATwo published clinical trials10 and real-world evidence from more than 50,000 users11 show that people who scan more frequently spend less time in hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) while having improved average glucose levels, demonstrating improved glucose control overall.Results from the IMPACT clinical trial, which was recently published in the medical journal The Lancet,11 showed that people with diabetes using the FreeStyle Libre system spent 38 percent less time in hypoglycemia as compared to people who managed their glucose with traditional self-monitoring of blood glucose systems (SMBG).Data from the study showed that using the FreeStyle Libre system contributes towards better management of hypoglycemia without increasing HbA1c (an average measurement of glucose levels in the blood over the past 90 days, typically understood in the industry to be the gold standard of measuring overall glucose control) versus SMBG, supporting FreeStyle Libre system as a safe and successful replacement for the need for routine finger sticks1 as a tool for managing diabetes."Hypoglycemia is the main barrier to attaining optimum glucose control in persons with insulin-treated diabetes. Moreover, hypoglycemic events can not only lead to adverse clinical outcomes, including cardiovascular events and death, but they can also incur significant emergency healthcare costs," said Prof. Jan Bolinder, M.D., FRCPE, Karolinska Institutet, Stockholm, Sweden, and chief investigator for the IMPACT study. "This clinical trial has proven that patients will test more often when they have an easier and more convenient way to do so utilizing a device like FreeStyle Libre, and that leads to them ultimately being healthier, which is our goal for our patients."FREESTYLE LIBRE AVAILABILITYAbbott's FreeStyle Libre system is expected to be available in Canada in the coming months. For more information about FreeStyle Libre, visit FreeStyleLibre.ca.
ALK: Five-year GRAZAX® Asthma Prevention (GAP) Trial Reveals Benefits of Early Treatment Intervention in Children
The disease modifying property of GRAZAX® (SQ® grass SLIT-tablet) resulted in long-term effect on allergic rhinoconjunctivitis (ARC) and prevented asthma symptoms, even two years after end of treatment in children with grass pollen ARC and no existing signs or symptoms of asthma Younger children had a higher probability of developing asthma. The younger the children were at treatment-start, the greater the percentage was prevented from having asthma symptoms and using asthma medication during the two-year follow-up period post discontinuation of treatment Evidence in asthma continues to build for latest generation of allergy immunotherapy treatments ALK (ALKB: DC / OMX: ALK B / AKABY / AKBLF) today released further analysis of data from its landmark five-year GRAZAX® Asthma Prevention (GAP) clinical trial in children. The analysis, which appears online in press in The Journal of Allergy and Clinical Immunology, shows that the benefits of GRAZAX® in prevention of asthma symptoms were even more pronounced when treatment was initiated at an earlier age.(Logo: http://photos.prnewswire.com/prnh/20160420/357628LOGO ) The GAP trial, which is the largest double-blind, placebo-controlled trial ever conducted in allergy immunotherapy in a paediatric population, was initiated in 2009 to investigate the effect of ALK's sublingual grass allergy immunotherapy (SLIT) tablet, GRAZAX®, on the risk of developing asthma when compared with placebo treatment. The trial involved 812 children aged 5-12 years at 101 sites in 11 European countries and comprised a three-year treatment phase with a two-year follow-up phase.The primary trial endpoint was the time to a first diagnosis of reversible impairment of lung function. The hypothesis was that fewer children given GRAZAX® would receive this diagnosis or that they would be diagnosed later than subjects in the placebo group.This primary endpoint was not met and the trial indicated that an appropriate asthma diagnosis in this particular population should not be based on a single time point evaluation but rather rely on a combined clinical assessment obtained over a longer observation period, which is normally done in daily practice. However, the trial did reveal several advantages of early treatment of children with GRAZAX®. Including:GRAZAX® significantly reduced the proportion of children experiencing asthma symptoms or using asthma medication - an effect that was observed year round and sustained for two years after end of treatment The younger the children were at treatment initiation, the greater the percentage of children avoiding asthma symptoms and the need for symptomatic asthma medication during the follow-up period The disease modifying effect on ARC in children was verified The GAP trial also confirmed that the safety and tolerability of GRAZAX® were favourable and in line with previous studies, with no new or unexpected findings.Erkka Valovirta, Adjunct professor of clinical and paediatric allergology, University of Turku, Finland, said: "The landmark GAP trial uncover valuable data about allergic asthma and the potential for preventing it with a new class of clinically proven allergy immunotherapy products such as GRAZAX®. These data illustrates the importance of early intervention with the right treatment for children who are at risk of developing this serious condition."Asthma affects an estimated 300 million individuals worldwide and is considered a serious global health problem affecting all age groups. It is one of the most common chronic childhood diseases and can impose a considerable burden on patients, their families, and health care systems. Allergic rhinoconjunctivitis is a recognised risk factor for asthma development.GRAZAX® is one of a new generation of allergy immunotherapy treatments that show benefits in respiratory allergy. It reduces ARC symptoms and the need for allergy pharmacotherapy. In addition, the latest GAP data indicate that the disease modifying properties of GRAZAX® extends to prevent the development of asthma symptoms in children with grass pollen ARC. GRAZAX® is today marketed in Europe and Australia as the only product with an ARC disease modifying effect. In North America GRAZAX® is available under the brand name GRASTEK®.In 2015, ALK's ACARIZAX® - a sister product to GRAZAX® used in the treatment of house dust mite allergy - became the first SLIT-tablet to be approved for use in patients with house dust mite allergic asthma in Europe. In February 2017, clinical data for ACARIZAX® led, for the first time, to the addition of allergy immunotherapy as a recommended additional treatment option in the Global Initiative for Asthma (GINA) report: Global Strategy for Asthma Management and Prevention.
Novartis receives EU approval for first-line use of Zykadia® in ALK-positive advanced non-small cell lung cancer (NSCLC)
In ALK-positive advanced NSCLC patients, Zykadia demonstrated superior median progression-free survival (PFS) compared to SOC chemotherapy with maintenance Zykadia benefit was also seen in patients with brain metastases Approximately 3-7% of all patients with NSCLC have an ALK gene rearrangement Basel, June 29, 2017 - Novartis today announced the European Commission approved expanding the use of Zykadia® (ceritinib) to include the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive. Approval follows a positive opinion granted in May by the Committee for Medicinal Products for Human Use (CHMP), and is applicable to all 28 European Union member states plus Iceland, Lichtenstein, and Norway. The first-line approval of Zykadia is based on results from an open-label, randomized, multicenter, global, Phase III trial, ASCEND-4. The study met its primary endpoint, demonstrating a 45% reduction in the risk of disease progression in the Zykadia arm, compared to the chemotherapy arm (hazard ratio [HR] = 0.55 [95% confidence interval (CI): 0.42, 0.73; one-sided p value <0.0001]). Patients treated with first-line Zykadia had a median progression-free survival (PFS) of 16.6 months (95% CI: 12.6, 27.2), compared to 8.1 months (95% CI: 5.8, 11.1) for patients treated with standard first-line pemetrexed-platinum chemotherapy with pemetrexed maintenance. Overall intracranial response rate (OIRR) in patients with measurable brain metastases at baseline and at least one post-baseline assessment was 72.7% (95% CI: 49.8, 89.3; n = 22) for patients treated with Zykadia, versus 27.3% (95% CI: 10.7, 50.2; n = 22) for patients treated with chemotherapy. The whole body overall response rate (ORR) was 72.5% (95% CI: 65.5, 78.7; n = 189) in patients treated with Zykadia. Further, patients without brain metastases at screening receiving Zykadia experienced a median PFS of 26.3 months (95% CI: 15.4, 27.7), compared with 8.3 months (95% CI: 6.0, 13.7) among patients treated with chemotherapy (HR = 0.48 [95% CI: 0.33, 0.69]). Among patients with brain metastases at screening, the median PFS was 10.7 months (95% CI: 8.1, 16.4) in the Zykadia group, versus 6.7 months (95% CI: 4.1, 10.6) in the chemotherapy group (HR = 0.70 [95% CI: 0.44, 1.12]). "Today's EC approval of Zykadia as a first-line treatment of ALK+ non-small cell lung cancer is an important step forward for patients with this type of serious disease," said Bruno Strigini, CEO, Novartis Oncology. "Our commitment to innovation in lung cancer will continue and we look forward to providing additional advancements for patients as the incidence of the disease grows around the world." In May, US Food and Drug Administration (FDA) approved the expanded use of Zykadia to include the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive, as detected by an FDA-approved test. Novartis Commitment to Lung Cancer Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer combined, and an estimated 1.8 million new cases of lung cancer are diagnosed each year,. Over the past decade, Novartis Oncology's research has supported the evolution of treatment approaches for patients living with mutation-driven types of lung cancer. The company continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds that target genomic biomarkers in NSCLC. About ASCEND-4 ASCEND-4 is a Phase III randomized, open-label, multicenter, global clinical trial to evaluate the safety and efficacy of Zykadia compared to standard chemotherapy, including maintenance, in adult patients with Stage IIIB or IV ALK-positive advanced NSCLC who received no prior therapy for their advanced disease. Patients received Zykadia orally at 750 mg/daily or standard pemetrexed-based platinum doublet chemotherapy (pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5-6) for four cycles followed by pemetrexed maintenance. Of 376 patients, 189 (59 with brain metastases) were randomized to Zykadia and 187 (62 with brain metastases) to chemotherapy. Approximately 59.5% of patients with measurable brain metastases at baseline did not have prior radiation therapy, the current standard of treatment for baseline brain metastases. One hundred and five (105) patients out of the 145 patients (72.4%) that discontinued treatment in the chemotherapy arm received subsequent ALK inhibitor as first antineoplastic therapy. Of these patients 81 received Zykadia. The most common adverse reactions in ASCEND-4 (incidence >=25% all grades) were diarrhea (85%), nausea (69%), vomiting (67%), fatigue (45%), abdominal pain (40%), decreased appetite (34%) and cough (25%). Grade 3/4 adverse reactions (incidence >=2%) were fatigue (7%), vomiting (5%), diarrhea (4.8%), abdominal pain (3.7%), weight loss (3.7%), nausea (2.6%) and prolonged QT interval (2.6%). The most common laboratory abnormalities in ASCEND-4 (incidence >=25% all grades) were increased ALT/AST (91%/86%), increased GGT (84%), increased alkaline phosphatase (81%), creatinine increase (77%), anemia (67%), hyperglycemia (53%), decreased phosphate (38%), increased amylase (37%) and neutropenia (27%). Grade 3/4 laboratory abnormalities (incidence >=2%) were increased GGT (49%), ALT/AST (34%/21%), increased alkaline phosphatase (12%), hyperglycemia (10%), increased amylase (8%), increase lipase (6%), creatinine increase (4.2%), anemia (4.2%), decreased phosphate (3.7%) and neutropenia (2.1%).
New Data Reaffirm Clinically Meaningful Benefit of SPINRAZA® (nusinersen) in Individuals with Spinal Muscular Atrophy Across Disease Severity
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Biogen (NASDAQ: BIIB) will present robust efficacy and safety data from Phase 2 and 3 SPINRAZA® (nusinersen) studies at the Cure SMA 2017 Annual SMA Conference in Orlando, Fl, June 29 – July 2, 2017. The breadth of data presented reinforces the significant and clinically meaningful efficacy of SPINRAZA on the achievement of motor milestones and measures of motor function across a broad range of individuals with spinal muscular atrophy (SMA), as well as on survival endpoints in infantile-onset SMA.“Data presented at the Cure SMA 2017 Annual SMA Conference further demonstrate the significant impact of SPINRAZA and the benefits of early treatment initiation. We are encouraged to see unprecedented motor function gains in infants on permanent ventilation and a continued favorable benefit-risk profile across a broad population including no increase in risk of adverse events in children who have developed scoliosis.” said Wildon Farwell, M.D., M.P.H., senior medical director, Clinical Development, Biogen. “As part of our mission to make a meaningful difference in the lives of those affected by SMA, we continue to collect and evaluate data to provide a deeper understanding of the impact of SPINRAZA across SMA populations and share those results with the SMA community.”New SPINRAZA Data Show Robust Efficacy and Safety Across Broad Range of Individuals with SMA In an analysis of the Phase 3 ENDEAR end of study results, a greater proportion of infants with SMA on permanent ventilation treated with SPINRAZA demonstrated clinical benefits compared to untreated infants.End of study data from both the Phase 3 ENDEAR and CHERISH studies further demonstrate that earlier SPINRAZA treatment in individuals with SMA may lead to improved outcomes. In individuals with shorter disease durations (i.e., generally younger at symptom onset), infants in ENDEAR demonstrated a lower risk of death or permanent ventilation and children in CHERISH demonstrated greater motor function improvement from baseline to 15 months compared to untreated individuals.In addition, further results from the interim analysis of the Phase 2 NURTURE study highlight the clinically meaningful efficacy of SPINRAZA on event-free survival, measures of motor function and achievement of motor milestones when administered to infants with genetically-diagnosed SMA before symptom onset.“New SPINRAZA data continue to reinforce the positive results seen in clinical studies and in my own practice,” said Thomas Crawford, M.D., co-director, Muscular Dystrophy Association Clinic at Johns Hopkins Medicine. “The SPINRAZA clinical development program demonstrates the impact of early treatment. The additional NURTURE data extends this finding by showing substantial improvements in motor milestones, generally consistent with normal development among infants with SMA who have yet to manifest symptoms before they were treated with SPINRAZA.”SPINRAZA demonstrated a favorable benefit-risk profile, with commonly reported adverse events consistent with those expected in the general SMA population or related to a lumbar puncture procedure. Safety data involving the intrathecal administration of SPINRAZA showed the incidence and nature of the most common lumbar puncture-related adverse events were similar in children with later-onset SMA with or without scoliosis in the clinical studies.
The U.S. Food and Drug Administration today allowed marketing of ClearLLab Reagents (T1, T2, B1, B2, M), the first agency authorized test for use with flow cytometry to aid in the detection of several leukemias and lymphomas, including chronic leukemia, acute leukemia, non-Hodgkin lymphoma, myeloma, myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN). “This represents a major step forward for the hematology-oncology community,” said Alberto Gutierrez, Ph.D., Director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “Laboratories and health care professionals now have access to an FDA-validated test that provides consistent results to aid in the diagnoses of these serious cancers.”According to the National Cancer Institute, leukemia is a cancer of the blood that originates in immature blood cells (also called leukocytes), which crowd out the healthy blood cells in the bone marrow. Leukemia occurs most often in adults older than 55 years, but it is also the most common cancer in children younger than 15 years. Lymphoma is a cancer that begins in the cells of the lymph system, a part of the immune system that helps the body fight infection and disease.The ClearLLab test is used to detect cancerous cells in blood, bone marrow and lymph nodes, and it also provides laboratories and clinicians with information about what type of leukemia or lymphoma is present. It works by marking proteins found on the surface of cells with fluorescent dyes for further analysis on an instrument known as a flow cytometer.The FDA reviewed data for the ClearLLab test through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device. Its authorization was supported by a study designed to demonstrate the test’s performance, which was conducted on 279 samples at four, independent clinical sites. The study compared the test’s results to alternative detection methods used by the clinical sites. The study showed that the results of the test aligned with the study site’s final diagnosis 93.4 percent of the time and correctly detected that there was a cancer presence (i.e., cancer abnormality) 84.2 percent of the time.Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the test’s accuracy, reliability and clinical relevance. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for the ClearLLab Reagents and similar tests used to aid in the diagnosis of leukemias and lymphomas. The special controls also describe the least burdensome regulatory pathway for future developers of similar diagnostic tests for leukemias and lymphomas.Users of the new test are advised that results must be reviewed by a trained professional.The FDA granted market authorization of ClearLLab Reagents (T1, T2, B1, B2, M) to Beckman Coulter, Inc.The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Vectibix Demonstrated an Improvement in Overall Survival in Patients With Wild-Type RAS Metastatic Colorectal Cancer Predictive Biomarkers Allow Physicians to More Accurately Identify Treatments to Potentially Optimize Cancer Care Approved Companion Diagnostic Tool Strengthens Precision Medicine Approach THOUSAND OAKS, Calif. , June 29, 2017 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration ( FDA ) has approved the supplemental Biologics License Application (sBLA) for Vectibix® (panitumumab) for patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA -approved test for this use) metastatic colorectal cancer (mCRC) as first-line therapy in combination with FOLFOX and as monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy. Vectibix is the first-and-only fully human monoclonal anti-epidermal growth factor receptor (EGFR) antibody approved by the FDA for this patient population. As part of this new indication, the FDA approved the first multigene, next-generation sequencing-based test to identify the RAS mutation status of a patient's tumor. Next-generation sequencing is a novel diagnostics test technique that makes a more personalized medicine approach possible. This companion diagnostic helps physicians identify patients that are more likely to benefit from treatment with Vectibix. "Of the few biomarkers in colorectal cancer, RAS mutation status provides actionable information when deciding on a first-line treatment option in mCRC patients," said Marwan G. Fakih , M.D., co-director of the Gastrointestinal Cancer Program at City of Hope, Duarte, Calif. "Panitumumab has demonstrated a significant overall survival benefit to patients whose mCRC does not have mutations in RAS, providing physicians with a novel targeted treatment option and allowing us to develop a personalized approach as we help patients fight this devastating disease." The full approval for Vectibix as a treatment for patients with wild-type KRAS mCRC was based on results from the Phase 3 PRIME and ASPECCT trials. The approval of a refined indication for the treatment of patients with wild-type RAS mCRC was based on a retrospective analysis from the PRIME study and prospective, pre-defined analyses from the Phase 3 '0007 study. The '0007 study evaluated the efficacy of Vectibix plus best supportive care (BSC) versus BSC alone in patients with chemorefractory, wild-type KRAS mCRC. Data from a key secondary endpoint showed that patients with wild-type RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC treated with Vectibix plus BSC resulted in a statistically significant improvement in overall survival (OS) of 10 months compared to 6.9 months for patients treated with BSC alone (HR=0.70; 95 percent CI: 0.53, 0.93, p=0.0135). The safety profile of Vectibix in patients with wild-type RAS mCRC is consistent with that seen previously in patients with wild-type KRAS mCRC. "Every patient with cancer is unique, and we are committed to utilizing cutting-edge science and technology to target treatments to the patients more likely to benefit," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "This approval for Vectibix reinforces the significance of biomarker testing as a treatment planning tool in metastatic colorectal cancer and further validates the potential for precision medicine to optimize patient outcomes." Most common adverse reactions (= 20 percent) of Vectibix as monotherapy are skin rash with variable presentations, paronychia, fatigue, nausea and diarrhea. Most common adverse reactions (= 20 percent) with Vectibix plus FOLFOX are diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus and dry skin. The most common serious adverse reactions (= 2 percent difference between treatment arms) were diarrhea and dehydration. About Colorectal Cancer Colorectal cancer is the third most common cancer found in both men and women in the U.S., with approximately 135,000 new cases estimated to be diagnosed in 2017.1 Approximately 20 percent of colon cancers are diagnosed at the metastatic stage when the disease has already spread to distant organs, a diagnosis associated with only a 12 percent five-year survival rate.2 Using molecular approaches to identify unique genetic signatures in mCRC has the potential to help improve treatment outcomes.3 About the '0007 Study (NCT01412957) This Phase 3 global, multicenter, randomized, open-label study was designed to evaluate OS with Vectibix and BSC compared to BSC alone in patients with chemorefractory wild-type KRAS (exon 2) mCRC. The key efficacy analysis of the study showed that Vectibix plus BSC (n=189) was statistically significant to BSC alone (n=188). Patients with wild-type KRAS (exon 2) mCRC treated with Vectibix plus BSC achieved a median OS of 10 months compared to 7.4 months for patients treated with BSC alone (HR=0.73; 95 percent CI: 0.57, 0.93, p=0.0096). In patients with mutant RAS mCRC, no differences in OS or progression-free survival (PFS) were observed between the treatment arms [OS HR=0.99 (95 percent CI: 0.49, 2.00); PFS HR=1.03 (95 percent CI: 0.56, 1.90)]. No new safety signals were seen in the '0007 study. The safety profile was comparable to the known safety profile of Vectibix when administered as a single agent. About the PRIME Study PRIME was a randomized, Phase 3, open-label study of Vectibix and FOLFOX combination therapy versus FOLFOX monotherapy in 1,183 adults with untreated mCRC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. The primary endpoints were PFS and OS. The PRIME study showed that patients with wild-type KRAS tumors (exon 2) achieved statistically significant improvement in PFS with Vectibix and FOLFOX versus FOLFOX alone (9.6 versus 8.0 months [HR=0.80; 95 percent CI: 0.66, 0.97, p=0.02]) and a significant 4.4 month improvement in OS versus FOLFOX alone (23.8 versus 19.4 months [HR=0.82, 95 percent CI: 0.70, 0.98]). Analyses from the PRIME study evaluated the treatment effect of Vectibix plus FOLFOX compared with FOLFOX alone in the wild-type RAS subgroup and found that Vectibix plus FOLFOX extended the prespecified major efficacy measure of PFS versus FOLFOX alone, 10.1 months versus 7.9 months, respectively (HR=0.72; 95 percent CI: 0.58, 0.90). The study demonstrated that the median OS for patients treated with Vectibix plus FOLFOX was 25.8 months versus 20.2 months for those treated with FOLFOX alone (HR=0.77; 95 percent CI: 0.64, 0.94). There were no OS or PFS benefit in Vectibix-treated patients with mutant RAS mCRC. About the ASPECCT Study ASPECCT was a global, randomized, multicenter, open-label, Phase 3 non-inferiority trial designed to compare the effect of Vectibix versus Erbitux® (cetuximab) on OS for monotherapy treatment of 1,010 patients with EGFR-expressing, chemorefractory wild-type KRAS (exon 2) mCRC. The ASPECCT study met its primary endpoint of non-inferiority for improving OS in patients taking Vectibix (n=499) versus Erbitux (n=100) as a single agent for the treatment of mCRC in patients with wild-type KRAS tumors who have not responded to chemotherapy. Patients treated with Vectibix demonstrated an OS of 10.4 months versus 10 months for patients treated with Erbitux (HR=0.97; 95 percent CI: 0.84-1.11). About Vectibix® (panitumumab) Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC. In June 2017 , the FDA approved a refined indication for Vectibix for use in in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA -approved test for this use) mCRC. Important U.S. Product Information Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA -approved test for this use) metastatic colorectal cancer (mCRC): As first-line therapy in combination with FOLFOX. As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. Limitation of Use: Vectibix® is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown. WARNING: DERMATOLOGIC TOXICITY Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 or higher) in 15% of patients receiving Vectibix monotherapy. In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix®. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix® for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix®. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix®. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (eg, Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix® for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix® concerning dermatologic toxicity are provided in the product labeling. Vectibix® is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS." Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix® in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix® and FOLFOX versus FOLFOX alone. Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix® treatment, periodically during Vectibix® treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate. In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix® administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions. Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix® in combination with chemotherapy. Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix®. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix®. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix® therapy. Discontinue Vectibix® therapy if ILD is confirmed. In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix® versus the risk of pulmonary complications must be carefully considered. Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix®. Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix® use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix® for acute or worsening keratitis. In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix®-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0). NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix®-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix®-treated patients. As a result of the toxicities experienced, patients randomized to Vectibix®, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy. Vectibix® can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix®. In monotherapy, the most commonly reported adverse reactions (= 20%) in patients with Vectibix® were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea. The most commonly reported adverse reactions (= 20%) with Vectibix® + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (= 2% difference between treatment arms) were diarrhea and dehydration. To see the Vectibix® Prescribing Information, including Boxed Warning visit www.vectibix.com. About Amgen's Commitment to Oncology Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen's supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines. About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.