Betnovate (Celestan biphase)
Betnovate is used to help relieve redness, itching, swelling, or other discomfort caused by skin conditions.
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Betnovate is used to help relieve redness, itching, swelling, or other discomfort caused by skin conditions.
Active Ingredient: Betamethasone
Betnovate (Celestan biphase) as known as: Akriderm, Alphatrex, Alpider, Anflavate, Antebate, Antroquoril, Asisone, Beben, Bectmiran, Bedicort g, Behealth, Beloderm, Belogent, Belosalic, Bemetson, Bemon, Benoson, Bentelan, Beprogel, Beprosone, Beprospen, Berbesolone, Besone, Bestflan, Beta cream, Beta micoter, Beta ointment, Béta septigen, Beta-micoter, Beta-val, Betabioptal, Betacap, Betacort, Betacorten, Betacream, Betacrem, Betaderm, Betadermic, Betafloroto, Betafoam, Betafusin, Betagalen, Betagentam, Betaject, Betalotio winthrop, Betam-ophtal, Betamatic, Betamed, Betamesol, Betameson, Betamet, Betametasona, Betametha, Betamethason, Bétaméthasone, Betamethasonum, Betamil, Betanoid, Betapred, Betariem, Betasalbe ksk, Betaselemin, Betasid, Betasin, Betason, Betasone, Betasone-g, Betatape, Betatopic, Betatrex, Betaval, Betaval-n, Betavate, Betavet, Betazon, Betesil, Betnelan, Betnelan v, Betnesalic, Betnesol, Betnesol-v, Betneval, Betnevate, Betnoval g, Betnovat, Betoblock, Betodermin, Betonate, Betopic, Betricin, Betsolan, Bettamousse, Bevalex, Bevason, Biorinil, Blacor, Blamy, Buccobet, Calamiraderon, Camnovate, Celesdepot, Celesemine, Célestamine, Celestan, Celestan biphase, Celestana, Célestène, Celestoderm, Celeston, Celeston valerat, Celestone, Celestonvalerat, Celestovet, Cevicort, Chlocodemin, Cidoten, Cidoten inyectable, Cidoten rapilento, Cidoten-v, Cilestoderme, Clotrasone, Coid, Colergis, Cordes beta, Coritex, Corsaderm, Cortamine, Corteroid, Cortibet, Cortiderma, Cortiflam, Cortimax, Cortispec, Cortival, Cortixyl, Cortixyl depot, Cremirit, Cronocorteroid, Cronolevel, Dacam, Daivobet, Debion-vg, Deflatop, Deltalaf, Dermabet, Dermabiolene, Dermasone, Dermesone, Dermizol, Dermosol, Dermosol-dp, Dermosone, Derzid, Dexacort depot, Dexan g, Dexan-vg, Digenta, Diprocel, Diproderm, Diprofast, Diproform, Diproforte, Diprofos, Diprogenta, Diprolen, Diprolene, Dipronova, Diprophos, Diprosalic, Diprosan, Diprosis, Diprosone, Diprosone depot, Diprospan, Diprostène, Diprotop, Diprovate, Disopranil, Dovobet, Dppollon, Ecoval, Egerian, Eleuphrat, Emperacin, Erispan, Exabet, Exabetin, Eye rinderon, Eyebet, Fidagenbeta, Floderm, Flogozyme, Flosteron, Fluororinil, Fubecot, Fucibet, Fucicort, Fucicream, Fuciderm, Fungolisin nf, Fusibact b, Fusibet, Futasone, Galinocort, Garamat, Garasone, Gentalyn, Gentamicin, Gentasone, Gentavet, Gentocin, Helpoderm, Hicort, Histablock, Hizubot, Ijilone v, Infanal, Inflacor, Inflacor retard, Isotic betaracin, Itisona, Kamelyn, Keligroll, Krimbeson, Kuterid, Kuterid g, Labosona, Lazar, Lenasone, Lenovate, Linolacort, Linolosal, Lotricomb, Luricul vg, Luxiq, Maxivate, Medobeta, Metaskin-n, Methasol, Methovate, Movithiol, Multiderm, Mytaderm, Nilacelin, Nisagon, Nolcot, Norbet, Ocuson, Oftasona p, Ophtamesone, Ophtasone, Opizole, Osmoran, Otomax, Oviskin, Persivate, Prevason, Prevex b, Propiochrone, Propioform, Proson, Psorcutan, Puradesmin, Quiacort, Ratio-topilene, Ratio-topisalic, Ratio-topisone, Repivate, Rinbeta pf, Rinderon, Rinderon-dp, Rinderon-v, Rinesteron, Saccortin, Salgen plus, Salibet, Sanbetason, Scanderma, Septon, Seroderm, Sinacort, Skilone, Skizon-n, Soderm, Solu-celestan, Soluderme, Solusone, Sonigen, Spel, Steromien, Steronema, Supraproct, Suprasone, Suprastene, Taclonex, Tanderil, Taro-sone, Tokuderm, Topagen, Topicasone, Topiderm, Topik, Topizone, Uciderm, Uniflex, Vabeta, Valbet, Valecort, Valederm, Valerpan, Valisone, Valnac, Verilona, Viltern, Vista-methasone, Walacort, Xamiol, Zensoderm, Zestam
The current WHO phase of pandemic alert for Pandemic (H1N1) 2009 is post-pandemic.
In nature, influenza viruses circulate continuously among animals, especially birds. Even though such viruses might theoretically develop into pandemic viruses, in Phase 1 no viruses circulating among animals have been reported to cause infections in humans.
In Phase 2 an animal influenza virus circulating among domesticated or wild animals is known to have caused infection in humans, and is therefore considered a potential pandemic threat.
In Phase 3. an animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks. Limited human-to-human transmission may occur under some circumstances, for example, when there is close contact between an infected person and an unprotected caregiver. However, limited transmission under such restricted circumstances does not indicate that the virus has gained the level of transmissibility among humans necessary to cause a pandemic.
Phase 5 is characterized by human-to-human spread of the virus into at least two countries in one WHO region. While most countries will not be affected at this stage, the declaration of Phase 5 is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short.
Phase 6. the pandemic phase, is characterized by community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5. Designation of this phase will indicate that a global pandemic is under way.
During the post-peak period. pandemic disease levels in most countries with adequate surveillance will have dropped below peak observed levels. The post-peak period signifies that pandemic activity appears to be decreasing; however, it is uncertain if additional waves will occur and countries will need to be prepared for a second wave.
In the post-pandemic period. influenza disease activity will have returned to levels normally seen for seasonal influenza. It is expected that the pandemic virus will behave as a seasonal influenza A virus. At this stage, it is important to maintain surveillance and update pandemic preparedness and response plans accordingly. An intensive phase of recovery and evaluation may be required.
Phase I trials are the first stage of testing in human subjects, normally performed with a small group of healthy volunteers. This phase includes trials designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of a candidate drug.
In order to first test a candidate drug in humans, the pharmaceutical company responsible for the trial must obtain permission from the regulatory agency in each country in which the study is to be conducted. The application dossier includes all available information regarding the candidate drug, and is known as the Investigational New Drug Application (IND) in the USA, and the Clinical Trial Application (CTA) in the EU. The decision to grant permission to conduct a clinical trial is based on the preclinical data regarding safety, efficacy, pharmacology, and toxicology in animal models.ACTELION'S PHASE I PORTFOLIO: Related Links Downloads Lab Head, Chemistry
Celestan Side Effect Report#8457855-3
Retinopathy Of Prematurity. Low Birth Weight Baby. Neonatal Respiratory Distress Syndrome. Premature Baby
Celestan Side Effect Report#8457850-4
Retinopathy Of Prematurity. Premature Baby. Bronchopulmonary Dysplasia. Neonatal Respiratory Distress Syndrome. Low Birth Weight Baby
Celestan Side Effect Report#8457845-0
Premature Baby. Intraventricular Haemorrhage. Retinopathy Of Prematurity. Neonatal Respiratory Distress Syndrome. Low Birth Weight Baby
Celestan Side Effect Report#8457844-9
Low Birth Weight Baby. Intraventricular Haemorrhage. Neonatal Respiratory Distress Syndrome. Bronchopulmonary Dysplasia. Premature Baby. Retinopathy Of Prematurity
Celestan Side Effect Report#8415842-5
Oligohydramnios. Trigeminal Neuralgia. Maternal Exposure During Pregnancy. Premature Delivery
This is a report of a 41-year-old female patient (weight: NA) from Germany. suffering from the following health symptoms/conditions: NA, who was treated with Celestan Solubile (dosage: Unk, start time:Apr 28, 2009), combined with:
Celestan Side Effect Report#7952858-7
Gastrointestinal Infection. Bradycardia Foetal. Cervical Incompetence. Maternal Exposure During Pregnancy. Umbilical Cord Around Neck. Haemorrhagic Diathesis
This report suggests a potential Celestan Gastrointestinal Infection side effect(s) that can have serious consequences. A 29-year-old female patient (weight: NA) from Germany was diagnosed with the following symptoms/conditions: NA and used Celestan (dosage: NA) startingApr 01, 2011. After starting Celestan the patient began experiencing various side effects, including: Gastrointestinal Infection. Bradycardia Foetal. Cervical Incompetence. Maternal Exposure During Pregnancy. Umbilical Cord Around Neck. Haemorrhagic Diathesis Additional drugs used concurrently:
Celestan Side Effect Report#7685202-3
Haemorrhagic Diathesis. Maternal Exposure During Pregnancy. Cervical Incompetence. Gastrointestinal Infection
This Haemorrhagic Diathesis problem was reported by a consumer or non-health professional from Germany. A 29-year-old female patient (weight: NA) was diagnosed with the following symptoms/conditions: NA. OnApr 01, 2011 this consumer started treatment with Celestan (dosage: NA). The following drugs were being taken at the same time:
Celestan Side Effect Report#7331493-8
This Herpes Zoster side effect was reported by a health professional from Austria. A 70-year-old male patient (weight:NA) experienced the following symptoms/conditions: NA.The patient was prescribed Celestan Biphase (betamethasone Sodium Phosphate/acetate /00309501/) (drug dosage: Iv), which was initiated on NS. Concurrently used drugs: NA..After starting to take Celestan Biphase (betamethasone Sodium Phosphate/acetate /00309501/) the consumer reported adverse symptoms, such as: Herpes Zoster These side effects may potentially be related to Celestan Biphase (betamethasone Sodium Phosphate/acetate /00309501/). The patient was hospitalized.
Celestan Side Effect Report#6196697-9
This is a report of a 62-year-old female patient (weight: NA) from Austria. suffering from the following health symptoms/conditions: NA, who was treated with Celestan Biphase (betamethasone Sodium Phosphate/acetate) (dosage: NA, start time: NS), combined with: NA. and developed a serious reaction and side effect(s): Leukocytosis after the beginning of treatment. This case can indicate the possible existence of increased vulnerability to Celestan Biphase (betamethasone Sodium Phosphate/acetate) treatment in female patients, resulting in Leukocytosis side effect.
Celestan Side Effect Report#4565983-8
Buttock Pain. Depression. Intention Tremor. Nerve Injury. Sensorimotor Disorder
Note Your Observations
It is really important to keep track of your health symptoms, right from the time you start a new medicine. You can do it any way you prefer: in a notebook, in a computer file or using our online tool. You should also note down any other medicines you are taking at the same time, because there could be an interaction between these medicines.
Why Your Notes are Important
Your notes could be helpful in several ways:
You can use the following log form to write down important information, like the date and time you experienced a side effect and your symptoms, how strong the symptoms were, and any other medicines you were using.
Medicine Name and Dosage:
Other Medicine(s) or Treatment(s)
Scale: 1 = very mild to 10 = very bad
Side effects reports are analyzed to discover potential health product safety signals. Some important reactions may take an extremely long time to develop or occur infrequently. Continued monitoring of adverse reactions is thus essential to maintain a comprehensive safety and effectiveness profile of health products.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Celestan reports list potential signals of serious risks and new safety information that were identified using the FDA Adverse Event Reporting System (FAERS).
FAERS is a database that contains information on adverse event and medication errors reports submitted to FDA by healthcare professionals (such as physicians, pharmacists, nurses and others), consumers (such as patients, family members, layers and others) and manufacturers.
Side Effects reported to FDA: 10
Celestan safety alerts: No
Reported hospitalizations: 6Celestan Reviews
No reviews, be a first to report a side effect via side effect reporting form
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People with DSPS tend to fall asleep at very late times, and also have difficulty waking up in time for normal work, school, or social needs. DSPS is treatable, but cannot be cured. It is often mistaken for insomnia, and treated inappropriately.
DSPS is responsible for 7 -10% of cases of putative chronic insomnia in adults that show up at sleep clinics. The true number may be higher because of underdiagnosis.
It is hard to say how many people have DSPS. Published studies have used small sample sizes. A Norwegian study found the disorder affects less than 0.2% of adults. but other sources point to it being more common. Another study estimates 10% of those with apparent chronic insomnia actually have DSPS. DSPS is equally distributed among both sexes and is not linked to any familial patterns. DSPS usually begins after a change in the normal sleeping pattern. Patients usually report that they had previously stayed up nights; for example studying or taking night shifts.Lazy Bones
People with DSPS are sometimes viewed as lazy and lacking in ambition or drive. It is, of course, unfair to characterize them as such, but study of the personality of those with DSPS shows why this stereotype may be enforced by other issues. A personality study of young adults with DSPS shows they tend to score lower on the personality metric Conscientiousness than the general population. They also tend to be more neurotic and introverted.Pathology Presentation
DSPS patients are frequently mind-boggled with trying to find a way to fall asleep at a socially acceptable time. They often try several tactics to adjust including trying to go to sleep early, setting several alarm clocks to go off in the morning, getting others to wake them in the morning and the use of sleeping pills. Formal tracking through a polysomnogram, home monitoring device, or sleep diary shows such signs as: falling asleep after 2 am, plenty of sleep after sleep onset, waking up late during the day, and oversleeping on the weekends. Patients with DSPS are classic "night owls" and say they are at their optimal performance at night.Treatment
Methods that can be used
Treatment is meant to allow the person with DSPS to wake up at a given time feeling refreshed and functional.
"Dawn is when men of reason go to bed" - Ambrose Bierce - The Devil's Dictionary.
Advanced sleep phase disorder (ASPD ), also known as the advanced sleep-phase type (ASPT) of circadian rhythm sleep disorder or advanced sleep phase syndrome (ASPS), is a condition in which patients feel very sleepy and go to bed early in the evening (e.g. 6:00–8:00 p.m.) and wake up very early in the morning (e.g. around 3:00 a.m.).Symptoms
People with ASPD are unable to stay awake until their desired bedtime and unable to stay asleep until their desired waking time. They will complain to a sleep clinician of early morning insomnia and falling asleep early in the evening. When someone has advanced sleep phase disorder their melatonin levels and core body temperature will cycle hours earlier than an average person. [ 1 ] These symptoms must be present for at least three months in order to be correctly diagnosed.Epidemiology
ASPD is a rare disorder. It affects both men and women equally and has been determined to have a strong genetic link with 40–50% of people related to someone with ASPD having it themselves. As stated below, several genes have been discovered to have links with this syndrome and the body's circadian rhythms. Although it can be impairing, the syndrome is not necessarily unhealthy; most people don't seek help unless it starts to severely impact their social life.Treatment
Once diagnosed, ASPD can be treated with bright light therapy in the evenings or behaviorally with chronotherapy. Unlike other sleep disorders, ASPD does not disrupt normal functioning at work during the day and the patient does not complain of excessive daytime sleepiness. If their ASPD is causing people to lose out on evening activities, including putting their own normal children to bed, they may be able to force themselves to stay up later than their circadian rhythm requires. A sufferer of ASPD will still wake up very early and if this cycle continues it can lead to chronic sleep deprivation and other sleep disorders. [ 2 ]Familial advanced sleep phase syndrome
In 1999, Louis Ptáček's and Ying-Hui Fu 's research group at the University of California, San Francisco reported findings of a human circadian rhythm disorder showing a familial tendency. The disorder was characterized by a lifelong pattern of sleep onset around 7:30 p.m. and offset around 4:30 a.m. Among three lineages, 29 people were identified as affected with this familial advanced sleep-phase disorder (FASPD), and 46 were considered unaffected. The pedigrees demonstrated FASPD to be a highly penetrant, autosomal dominant trait. [ 3 ]
Two years after reporting the finding of FASPD, Ptáček's and Fu's groups published results of genetic sequencing analysis on a family with FASPD. They genetically mapped the FASPD locus to chromosome 2q where very little human genome sequence was then available. Thus, they identified and sequenced all the genes in the critical interval. One of these was Period2 (Per2). Sequencing of the hPer2 gene revealed a serine-to-glycine point mutation in the CKI binding domain of the hPER2 protein that resulted in hypophosphorylation of Per2 in vitro. [ 4 ]
In 2005, Fu's and Ptáček's labs reported discovery of a different mutation causing FASPD. This time, CKIδ was implicated, demonstrating an A-to-G missense mutation that resulted in a threonine-to-alanine alteration in the protein. [ 5 ] The evidence for both of these reported causes of FASPD is strengthened by the absence of said mutations in all tested control subjects and by demonstration of functional consequences of the respective mutations in vitro. Fruit flies and mice engineered to carry the human mutation also demonstrated abnormal circadian phenotypes although the mutant flies had a long circadian period while the mutant mice had a shorter period. [ 4 ] [ 5 ] The differences between flies and mammals that account for this difference are not known. Most recently, Ptáček and Fu reported additional studies of the human Per2 S662G mutation and generation of mice carrying the human mutation. These mice had a circadian period almost 2 hours shorter than wild-type animals. Genetic dosage studies of CKIδ on the Per2 S662G mutation revealed that CKIδ is having opposite effects on Per2 levels depending on the sites on Per2 that CKIδ is phosphorylating. [ 6 ]See also References
BMN-701 Meaningfully Improves Respiratory Endpoints
Phase 2/3 Switch Study Expected to Begin by December 2013
Conference Call and Webcast to Be Held Today at 5:00 p.m. ET
SAN RAFAEL, Calif. March 19, 2013 (GLOBE NEWSWIRE) -- BioMarin Pharmaceutical Inc. (Nasdaq:BMRN) announced today results from POM-001, the Phase 1/2 trial for BMN-701, a fusion protein of insulin-like growth factor 2 and acid alpha-glucosidase (IGF2-GAA) for the treatment of late-onset Pompe disease. The results exceeded the company's pre-specified requirements for proceeding to the next phase of development by showing that in the 20 mg/kg every other week dose cohort, three out of 16 patients, or 19 percent, had a greater than 75 meter improvement in 6-minute walk distance, and that there was a 14.1 percent relative improvement in Maximal Expiratory Pressure (MEP) and a 27.0 percent relative improvement in Maximal Inspiratory Pressure (MIP) from pre-treatment baseline to week 24, two important measures of overall respiratory muscle function and strength. Pending a review with regulatory authorities, the company expects to continue development of BMN-701 by initiating a Phase 2/3 switching trial by the end of 2013 in late-onset Pompe patients who have previously been treated with alglucosidase alfa (Myozyme ® /Lumizyme ® ).
"More than half of late-onset Pompe patients require ventilatory assistance, and many more patients have impairments directly related to weakness of breathing muscles. This means that a therapy that improves respiratory muscle function substantially would be important and welcome and could help delay premature death in Pompe disease," said Professor Benedikt Schoser of the Friederich-Baur Institute and speaker of the German working group for Pompe disease.
"The findings from this study point the way forward for a potentially meaningful advance in the management of late-onset Pompe patients. Pompe is a disease that destroys muscle tissue throughout the body, including the muscles of respiration. Maximal Expiratory Pressure (MEP) and Maximal Inspiratory Pressure (MIP) are direct measures of respiratory muscle function and likely an important indicator of a drug's effectiveness in this setting. The improvements in MEP and MIP that BMN-701 patients demonstrated is a unique and important finding," said Barry Byrne, M.D. Ph.D. Professor, Pediatrics and Molecular Genetics & Microbiology and Director, University of Florida Powell Center, and lead investigator for POM-001. "If treatment with BMN-701 results in improvements in these important respiratory functional measures in patients who have already experienced a maximal benefit from current therapy, BMN-701 could become an important treatment option," Byrne said.
Phase 1/2 Study: Efficacy and Safety
The mean improvement in 6-minute walk distance was approximately 22 meters for the 16 patients treated in the 20 mg/kg cohort. In addition, there were three super-responders, or 19 percent of patients, who experienced greater than a 75 meter improvement in 6-minute walk distance from baseline to week 24. For pulmonary function, mean improvement in percent predicted forced vital capacity (FVC) was 1.2 percent in absolute terms, or a 2.0 percent relative improvement from pre-treatment baseline to week 24. Mean improvement in maximum voluntary ventilation (MVV) was 2.9 L/min in absolute terms, or a 4.3 percent relative improvement from pre-treatment baseline to week 24. Mean improvement in percent predicted maximal expiratory pressure (MEP) was 5.1 percent in absolute terms, or a 14.1 percent relative improvement from pre-treatment baseline to week 24. Mean improvement in percent predicted maximal inspiratory pressure (MIP) was 11.0 percent in absolute terms, or a 27.0 percent relative improvement from pre-treatment baseline to week 24. The company conducted a responder analysis in which each patient was assigned a score of plus one for improvement of more than 10 percent and minus one for a decline of 10 percent in the domains of 6-minute walk test, MEP and MIP. Each patient's scores were aggregated by summing the individual domain scores for that patient. Thirteen of the 16 patients scored a plus one or greater; two patients had a score of 0, consistent with stabilization, and one patient declined in one domain.
Side effects for BMN-701 were generally consistent with those seen for other enzyme replacement therapies. The principal clinical adverse event was infusion-associated reaction in two patients, resulting in temporary drug interruption in one patient and drug withdrawal in one patient. Infusion-associated hypoglycemia, an expected pharmacologic effect of BMN-701, occurred in 13 patients in the 20 mg/kg cohort. All hypoglycemia events occurred during or within one hour of infusion, were transient and readily manageable through diet and predominantly asymptomatic.
Table: BMN-701 Phase 1/2 Results as Compared to LOTS Study*
*The LOTS trial (N Engl J Med 2010;362:1396-406) was a randomized, placebo-controlled trial of alglucosidase alfa, recombinant human GAA, for the treatment of late-onset Pompe's disease. Ninety patients who were eight years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg/kg) or placebo. The two primary endpoints were 6-minute walk distance and percentage of predicted forced vital capacity (FVC). Comparison to LOTS study data roughly estimated at week 26 are presented to provide additional information regarding BioMarin's decision making process for the continued development of BMN-701. As the trials were independently conducted and utilized different protocols, no inference should be made about the comparative efficacy of the products tested.
"We are excited by the findings of our first study of BMN-701 in previously untreated Pompe patients. We observed meaningful improvements in mean 6-minute walk distance and very substantial walk improvements for some patients, plus significant improvements in respiratory muscle strength. Importantly, there were improvements in one or more walk or respiratory domains in nearly all patients. Based on discussions with Pompe KOLs who have reviewed this data, we believe there will be broad interest to participate in our planned Phase 2/3 study," said Hank Fuchs, M.D. Chief Medical Officer of BioMarin.
Next Phase of Development: Phase 2/3 Study
The company expects to initiate a Phase 2/3 switching trial by the end of 2013 in late-onset Pompe patients who have previously been treated with alglucosidase alfa. Subject to discussions with health authorities, the proposed study design is a single arm trial, with treatment at 20 mg/kg administered every other week for 24 weeks. The company intends to use efficacy as measured by the respiratory parameter MIP as the primary endpoint. Secondary objectives include MEP and six-minute walk test, as well as safety. The study will be conducted with full scale material from a revised manufacturing process, which has improved process robustness and increased productivity.
POM-001 Phase 1/2 Study Design
The Phase 1/2 trial is an open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic and clinical activity of BMN-701 administered as an intravenous infusion every two weeks at doses of 5 mg/kg, 10 mg/kg and 20 mg/kg. The company enrolled 22 patients between the ages of 18 and 65 years old with late-onset Pompe disease for a treatment period of 24 weeks.
Conference Call Details
BioMarin will host a conference call and webcast today, Tuesday, March 19, 2013 at 5:00 p.m. ET. This event can be accessed on the investor section of the BioMarin website at www.BMRN.com .
Date: March 19, 2013
Time: 5:00 p.m. ET
U.S. / Canada Dial-in Number: (877) 303-6313
International Dial-in Number: (631) 813-4734
Conference ID: 24529793
Replay Dial-in Number: (855) 859-2056
Replay International Dial-in Number: (404) 537-3406
Conference ID: 24529793
About Pompe Disease
Pompe Disease is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme. The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system. Measurement of maximal inspiratory and expiratory pressures are used to assess pulmonary muscle function. Maximal inspiratory pressure (MIP) is the maximal pressure that can be produced by the patient trying to inhale through a blocked mouthpiece. Maximal expiratory pressure (MEP) is the maximal pressure measured during forced expiration through a blocked mouthpiece after a full inhalation. Current treatment options for Pompe disease include Lumizyme and Myozyme. On April 28, 2006 the US Food and Drug Administration approved a Biologic License Application (BLA) for Myozyme (alglucosidase alfa, rhGAA),the first treatment for patients with Pompe disease. On May 26, 2010 FDA approved Lumizyme, a similar version of Myozyme, for the treatment of late-onset Pompe disease. Lumizyme and Myozyme have the same generic ingredient (Alglucosidase Alfa). Myozyme is made using a 160-L bioreactor, while the Lumizyme uses a 4000-L bioreactor.
BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company's product portfolio comprises four approved products and multiple clinical and pre-clinical product candidates. Approved products include Naglazyme® (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin; Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride) Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck KGaA of Darmstadt, Germany; and Firdapse™ (amifampridine), which has been approved by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS). Product candidates include BMN-110 (N-acetylgalactosamine 6-sulfatase), formally referred to as GALNS, which successfully completed Phase III clinical development for the treatment of MPS IVA, PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase), which is currently in Phase II clinical development for the treatment of PKU, BMN-701, a novel fusion protein of insulin-like growth factor 2 and acid alpha glucosidase (IGF2-GAA), which is currently in Phase I/II clinical development for the treatment of Pompe disease, BMN-673, a poly ADP-ribose polymerase (PARP) inhibitor, which is currently in Phase I/II clinical development for the treatment of genetically-defined cancers, and BMN-111, a modified C-natriuretic peptide, which is currently in Phase I clinical development for the treatment of achondroplasia. For additional information, please visit www.BMRN.com. Information on BioMarin's website is not incorporated by reference into this press release.
This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. including, without limitation, statements about: the development of BioMarin's BMN-701 program generally, the timing and design of the planed Phase 3 trial of BMN-701, and expectations regarding the final results of the Phase 2 trial following final statistical analysis. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: differences in the final analysis of the data from the BMN-701 Phase 1/2 trial, results and timing of current and planned preclinical studies and clinical trials of BMN-701; the content and timing of decisions by the U.S. Food and Drug Administration, the European Commission and other regulatory authorities; BioMarin's ability to secure clinical trial sites to perform the Phase 3 trial and the ability to enroll patients into those trials; the ability to timely manufacture suitable clinical trial material using the revised manufacturing process and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Annual Report on Form 10-K for the Year ended December 31, 2012. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.
BioMarin®, Naglazyme®, Kuvan® and Firdapse™ are registered trademarks of BioMarin Pharmaceutical Inc.
Aldurazyme® is a registered trademark of BioMarin/Genzyme LLC.
Novartis has announced results from a Phase III study showing Afinitor®* (everolimus), when used as an adjunctive therapy, significantly reduced treatment-resistant seizures associated with tuberous sclerosis complex (TSC) compared to placebo 1. Patients in all treatment arms were also taking one to three anti-epileptic drugs (AEDs)1. The study, EXIST-3 (EXamining everolimus In a Study of TSC), is being presented during a plenary session at the 68th Annual Meeting of the American Academy of Neurology (AAN) (Abstract #32430, 9:00-11:00 a.m. PST) 1.
"Approximately 85% of individuals with TSC are affected by epilepsy at some point in their lives, yet nearly two-thirds of these patients do not achieve seizure control with available therapies, and may also experience other potentially serious consequences, such as neuropsychological, cognitive, social or learning disabilities," said Jacqueline A. French, MD, department of neurology, NYU Langone Medical Center and lead investigator of the EXIST-3 trial. "These findings are encouraging as this is the first clinical study demonstrating benefit specifically for TSC patients who suffer from treatment-resistant seizures."
In the study, 366 patients with TSC and treatment-resistant seizures were randomized to receive targeted concentrations of everolimus titrated to Low Exposure (LE; 3-7 ng/mL; n=117) or High Exposure (HE, 9-15 ng/mL; n =130), or placebo (n=119). The percentage reduction from baseline in seizure frequency was significantly greater among patients randomized to everolimus LE (29.3%, P=0.003; confidence interval [CI]=95%) and HE (39.6%, P 3,4,5. EXIST-3 study results show that everolimus is the first adjunctive therapy to achieve clinically significant seizure control in TSC patients and will be the basis for discussion with health authorities worldwide 1.
Everolimus works by inhibiting the mammalian target of rapamycin (mTOR), a protein that regulates multiple cellular functions. TSC is caused by mutations in the TSC1 or TSC2 genes, resulting in hyperactive signaling of the mTOR pathway which can lead to increased cellular growth and proliferation, neuronal hyper-excitability, abnormalities in cortical architecture and network function and impaired synaptic plasticity 6,7. Pre-clinical research suggests that hyperactive mTOR activity may influence several mechanisms of epileptogenesis, the gradual process by which the brain develops epilepsy 8.EXIST-3 study details
EXIST-3 is a Phase III, three-arm, randomized, double-blind, placebo-controlled study of the efficacy and safety of high and low exposure ranges of everolimus as adjunctive therapy in patients with TSC who have treatment-resistant seizures, defined as seizures persisting despite the use of two AEDs. The study enrolled male and female participants (ages 2.2-56.3) with clinically defined TSC, who were on stable doses of one to three AEDs for at least four weeks prior to a two month, pre-randomization, evaluation period 1.
The primary objective was to assess the effectiveness of adjunctive everolimus as compared to placebo in reducing seizures in patients with TSC who are taking one to three AEDs. Secondary objectives include the percentage of patients free from seizure during the maintenance period and change in seizure frequency.
The most frequent ≥10% all grade adverse events (AEs) reported with everolimus LE/HE vs placebo included stomatitis (28.2%/30.8% vs 3.4%), mouth ulceration (23.9%/21.5% vs 4.2%), diarrhea (17.1%/21.5% vs 5.0%), nasopharyngitis (13.7%/16.2% vs 16.0%), upper respiratory tract infection (12.8%/15.4% vs 12.6%), aphthous ulcer (4.3%/14.6% vs 1.7%) pyrexia (fever ) (19.7%/13.8% vs 5.0%), vomiting (12.0%/10.0% vs 9.2%), cough (11.1%/10.0% vs 3.4%) and rash (6.0%/10.0% vs 2.5%)1.About tuberous sclerosis complex
Tuberous sclerosis complex (TSC) may cause non-cancerous tumors to form in vital organs including the brain, kidney, heart, lungs and skin, as well as resulting disorders such as epilepsy, autism. cognitive impairment, behavioral problems and psychiatric disorders. Many people with TSC show evidence of the disease in the first year of life. However, because manifestations vary from person to person and can take years to develop, many children are not diagnosed until later in life, often with the onset of seizures, skin lesions or other significant symptoms, such as developmental delays. Because TSC is a lifelong condition, the latest professional diagnostic guidelines issued in 2012 advise that individuals be monitored by a doctor experienced with the disorder to ensure tumor growth or new symptoms are identified early 6,9.About everolimus
In the United States (US), everolimus is approved as Afinitor® for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Afinitor tablets and Afinitor Disperz™ are also indicated in the US in pediatric and adult patients with TSC for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.
In the European Union (EU), everolimus is approved as Votubia® for the treatment of adult patients with renal angiomyolipoma associated with TSC who are at risk of complications (based on factors such as tumor size or presence of aneurysm. or presence of multiple or bilateral tumors) but who do not require immediate surgery. The evidence is based on analysis in sum of angiomyolipoma volume. Votubia is also indicated in the EU for the treatment of patients with SEGA associated with TSC who require therapeutic intervention but are not amenable to surgery. The evidence is based on analysis of change in SEGA volume. Further clinical benefit, such as improvement in disease-related symptoms, has not been demonstrated.
Additionally, Afinitor is approved in 99 countries, including the US and throughout the EU, for locally advanced, metastatic or unresectable progressive neuroendocrine tumors (NET) of pancreatic origin and in the US for the treatment of adult patients with progressive, well-differentiated, nonfunctional NET of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. It is also approved in >120 countries including the US and EU for advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy (in the US, specifically following sunitinib and sorafenib). Afinitor is also approved in 102 countries including the US and EU for advanced HR+/HER2- breast cancer in combination with exemestane, after prior endocrine therapy.
Everolimus is also available from Novartis under the brand names Afinitor®, Certican® and Zortress® for use in oncology and transplant patient populations and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.
Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.
1. French, J, et al. Adjunctive everolimus therapy for the treatment of refractory seizures associated with tuberous sclerosis complex: results from a randomized, placebo-controlled, Phase 3 trial. American Academy of Neurology (AAN) 2016 Annual Meeting. Vancouver, Canada.
2. Chu-Shore C.J. et al. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia. 2010: 51(7): 1236-1241.
3. Budde, K. and Gaedeke, J. Tuberous sclerosis complex-associated angiomyolipomas: focus on mTOR inhibition. American Journal of Kidney Diseases. 2012:276-283.
4. Afinitor (everolimus) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; February 2016.
5. Afinitor (everolimus): EU Summary of Product Characteristics. Novartis; March 2016.
6. National Institute of Neurological Disorders and Stroke fact sheet. 2010.
7. Wong, M. Mammalian target of rapamycin (mTOR) pathways in neurological diseases. Biomed Journal. 2013; 36(2): 1-17.
8. Ostendorf, A. and Wong, M. mTOR inhibition in epilepsy: rationale and clinical perspectives. CNS Drugs. 2015: 91-99.
9. Northrup, H. et al. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatric Neurology. 2013; 49: 243-254.
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