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Shire begins Phase II ‘Vascugel’ trials
April 05,2012
Shire has kicked off two mid-stage trials assessing Vascugel – which is being developed by Shire under the name SRM003 – for enhancing blood vessel repair in patients with end-stage renal disease (ESRD) receiving haemodialysis.
Before patients can undergo haemodialysis, an arteriovenous (AV) access site must be created where blood can be removed, filtered and returned to the body.
In most cases, AV access is achieved through either an AV fistula (AVF), where the vein is connected directly to the artery, or an AV graft, where the vein and artery are connected via a synthetic tube.
Shire notes that there are around 100,000 AV fistulas and 60,000 AV grafts occurring annually in the US. But complications – such as infection, blood clots, and narrowing of the vessel – are common and frequently lead to access failure.
In fact, an estimated 60% of AV grafts fail after one year, requiring an additional procedure to restore flow or to create another access site, Shire said.
AYURVEDA SPOTLIGHT- BRAHMI
Bacopa monnieri
| Bacopa monnieri | |
|---|---|
 |
|
| Scientific classification | |
| Kingdom: | Plantae |
| (unranked): | Angiosperms |
| (unranked): | Eudicots |
| (unranked): | Asterids |
| Order: | Lamiales |
| Family: | Plantaginaceae |
| Genus: | Bacopa |
| Species: | B. monnieri |
Bacopa monnieri (waterhyssop, brahmi, thyme-leafed gratiola, water hyssop) is a perennial, creeping herb whose habitat includes wetlands and muddy shores. Brahmi is also the name given to Centella asiatica, particularly in North India, and Kerala where it is also identified in Malayalam as muttil (മുത്തിള്) or kodakan. This identification of brāhmī as C. asiatica has been in use for long in northern India, as Hēmādri’s Commentary on Aṣṭāṅgahṛdayaṃ (Āyuṛvēdarasāyanaṃ) treats maṇḍūkapaṛṇī (C. asiatica) as a synonym of brahmi, although that may be a case of mistaken identification that was introduced during the 16th century.
Brahmi been used by Indian Ayurvedic medical practitioners for almost 3000 years. The earliest chronicled mention of Brahmi is in several ancient Ayurvedic treatises including the Caraka Samhita (6th century A.D.), in which it is recommended in formulations for the management of a range of mental conditions including anxiety, poor cognition and lack of concentration, and the Bravprakash Var-Prakarana (16th century A.D.).
Description
Bacopa monnieri in Hyderabad, India.
The leaves of this plant are succulent and relatively thick. Leaves are oblanceolate and are arranged oppositely on the stem. The flowers are small and white, with four or five petals. Its ability to grow in water makes it a popular aquarium plant. It can even grow in slightly brackish conditions. Propagation is often achieved through cuttings.
Ecology
It commonly grows in marshy areas throughout India, Nepal, Sri Lanka, China, Taiwan, and Vietnam, and is also found in Florida, Hawaii and other southern states of the USA where it can be grown in damp conditions by the pond or bog garden.
Traditional uses
It has been used in traditional Ayurvedic treatment for epilepsy and asthma. It is also used in Ayurveda for ulcers, tumors, ascities, enlarged spleen, indigestion, inflammations, leprosy, anemia, and biliousness. This plant can be grown even as hydroponics using almost simple water.
Chemical constituents
Bacopa monnieri has many chemical constituents including alkaloids (brahmine and herpestine), saponins (d-mannitol and hersaponin, acid A, and monnierin), flavonoids (luteolin and apigenin). It also contains significant amounts of betulic acid, stigmasterol, beta-sitosterol, and bacopasaponins (bacosides A, bacosides B, bacopaside II, bacopaside I, bacopaside X, bacopasaponin C, bacopaside N2). The minor components include bacopasaponin F, bacopasaponin E, bacopaside N1, bacopaside III, bacopaside IV, and bacopaside V).
Pharmacology of chemical constituents
In rats, bacosides A enhance antioxidant defenses, increasing superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activity.Laboratory studies on rats indicate that extracts of the plant improve memory capacity. Some studies in mice suggest that ingestion of Bacopa for a 12 week period can significantly improve cognitive ability by accelerating the rate of learning and enhanced memory.The sulfhydryl and polyphenol components of Bacopa monnieri extract have also been shown to impact the oxidative stress cascade by scavenging reactive oxygen species, inhibiting lipoxygenase activity and reducing divalent metals.This mechanism of action may explain the effect of Bacopa monniera extract in reducing beta amyloid deposits in a mouse model of Alzheimer’s disease. B. monnieri has a demonstrated ability to reverse diazepam-induced amnesia in the Morris water maze test. The mechanism of this action is unknown. In some trials, bacopacide extract did not restore or enhance memory formation, but improved retention. In others, including a randomized clinical trial of 98 healthy older people (over 55 years), Bacopa significantly improved memory acquisition and retention. A 2012 systematic review found some evidence to suggest that Bacopa improves memory free recall, but there was a lack of evidence for enhancement of other cognitive abilities.
Brahmi may regulate antibody production by augmenting both Th1 and Th2 cytokine production.It may also cause a lower heart rate, and increase secretions in the stomach, intestines, and urinary tract. The increase in secretions may irritate ulcers and urinary tract obstructions.
No safety studies have been performed on brahmi’s use in humans. When a preparation of the plant was evaluated for safety and tolerability it showed no adverse effects but there were some reports of mild gastrointestinal symptoms.
However, participants in a 2001 double-blind study published in Psycho pharmacology experienced side effects including nausea, weakness and dry mouth while taking brahmi, notes the University of Michigan Health System. Brahmi could potentially cause elevated thyroid-hormone levels and decreased sperm counts. Therefore, taking brahmi should be avoided if you have a thyroid condition or are taking thyroid replacement therapies and other medications that affect thyroid function.
Aqueous extract of Bacopa monnieri (Brahmi) has been reported to reversibly suppress spermatogenesis and fertility in male mice with at a dose of 250 mg/kg body weight/day for 28 and 56 days(equivalent to 1.54 g/day for a 76kg male, when properly controlling for animal to human conversions ) Parameters of motility, viability, morphology, and number of spermatozoa in cauda epididymidis returned to baseline 56 days after treatment cessation.
The plant is known by many names in many international languages, including:
- ബ്രഹ്മി in Malayalam
- நீர்ப்பிரமி (Niirpirami)/ Valaarai in Tamil
- ผักมิ (Phak mi), พรมมิ (Phrommi) in Thai
- Lunuwila in Sinhalese (Sri Lanka)
- ae’ ae’ in Hawaiian (Hawaii)
- Rau Đắng in Vietnamese
- פְּשֵטָה שרועה (“psheta sru’a”) in Hebrew\
- conclusions
- Brahmi is a plant that has been used in traditional Indian medicine (Ayurveda). Be careful not to confuse brahmi (Bacopa monnieri) with gotu kola and other natural medicines that are also sometimes called brahmi.Brahmi is used for Alzheimer’s disease, improving memory, anxiety, attention deficit-hyperactivity disorder (ADHD), allergic conditions, irritable bowel syndrome, and as a general tonic to fight stress.People also take brahmi to treat backache, hoarseness, mental illness, epilepsy, joint pain, and sexual performance problems in both men and women. It is also sometimes used as a “water pill.”
-
Brahmi Benefits
Brahmi is considered a nootropic agent, which is the term given to a drug that improves mental functions such as cognition, memory, intelligence, motivation, attention, and concentration. Brahmi has been used in ayurvedic medicine and in traditional treatments for a number of disorders, particularly those involving anxiety, intellect, and poor memory.
Recent major scientific reviews of the plant suggest that it has prominent action on the central nervous system, where it improves understanding, memory, intellect, and speech, and corrects aberrations of emotions, mood, and personality in an individual. Based on the results of human clinical trials, the nootropic effects of Brahmi are thought to manifest after chronic dosing (i.e. 12 weeks) rather than acute (i.e. single day). Studies in humans have shown that chronic administration of Brahmi results in improvements in working memory, visual information processing, learning rate and anxiety.
In India, Brahmi is currently recognized as being effective in the treatment of mental illness and epilepsy. In certain parts of India, Brahmi is believed to be an aphrodisiac; in Sri Lanka, under the name of Loonooweella, Brahmi is prescribed for fevers; in the Philippines, it is used as a diuretic.
-
How does it work?
Brahmi might increase certain brain chemicals that are involved in thinking, learning, and memory. Some research suggests that it might also protect brain cells from chemicals involved in Alzheimer’s disease.
PHASE 3-Afatinib for locally advanced, recurrent or metastatic head and neck squamous cell carcinoma
Afatinib
Boehringer Ingelheim Pharmaceuticals.
Afatinib (Tomtovok; BIBW2992) Boehringer Ingelheim Pharmaceuticals., is a selective, potent, irreversible inhibitor of the ErbB family. The compound irreversibly binds to its targets and has potential for broader anti-tumour activity against receptors with acquired mutations which are resistant to first-generation inhibitors. Afatinib is intended for treatment of locally advanced, recurrent or metastatic HNSCC. Afatinib is administered orally at a starting dose of 40mg once daily. The dose may be increased to 50mg and/or reduced to 30mg, or 20mg depending on response and adverse effects
afatinib may provide an additional treatment option for this patient group who currently have limited effective therapeutic options. It has the potential to increase length of survival in this patient group.
Afatinib, Tomtovok, previously Tovok) is a candidate drug against non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim.As of July 2012, it is undergoing Phase III clinical trials for this indication and breast cancer, as well as Phase II trials for prostate and head and neck cancer, and a Phase I glioma trial. Afatinib is not a first-line treatment; it is only used after other therapies have failed.
In October 2010 a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug.Fall 2010 interim results suggested the drug extended progression-free survivalthreefold compared to placebo, but did not extend overall survival. In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.
Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive breast cancer) were described as promising by the authors, with 19 of 41 patients achieving benefit from afatinib. Double-blind Phase III trials are under way to confirm or refute this finding. Her2-negative breast cancers showed limited or no response to the drug.
Afatinib covalently binds to cysteine number 797 of the epidermal growth factor receptor (EGFR) via a Michael addition (IC50 = 0.5 nM).
Phase III trial of lupus drug Benlysta (belimumab) in patients with ANCA (Anti-neutrophil Cytoplasmic Antibodies) positive vasculitis
3 mar 2013
GSK, the company said it has kicked off a Phase III trial of its lupus drug Benlysta (belimumab) in patients with ANCA (Anti-neutrophil Cytoplasmic Antibodies) positive vasculitis, a condition characterised by inflammation of the blood vessels.
The multicentre, multi-national, randomised, double-blind study will assess the drug’s efficacy and safety in combination with azathioprine for the maintenance of remission in patients with a particular type of vascultitic disease called ANCA associated Vasculitis (Granulomatosis with Polyangiitis (Wegener’s) or microscopic polyangiitis).
Belimumab (trade name Benlysta, previously known as LymphoStat-B) is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS) B cells are responsible for part of the normal immune response, and also for the over-aggressive immune response in autoimmune diseases like systemic lupus erythematosus (SLE).
Belimumab is approved in the United States, Canada and Europe for treatment of SLE. However, the major phase III trials excluded the more severe cases of SLE with kidney and brain damage, so its effectiveness has not been demonstrated in those cases. A Phase III study for SLE patients with kidney disease is now recruiting.
U.S. F.D.A. reviewers were concerned that belimumab is only “marginally” effective, and that there were more deaths in the treatment group.
Phase II trials of belimumab for rheumatoid arthritis were unsuccessful. Phase II trials for Sjögren’s Syndrome were more successful.
Belimumab was developed by Human Genome Sciences (HGS) and Cambridge Antibody Technology. GlaxoSmithKline acquired HGS, took belimumab through Phase III clinical trials, and markets belimumab.
Phase 3-Volasertib for acute myeloid leukaemia in patients ineligible for intensive induction therapy
Volasertib (BI 6727) for Acute myeloid leukaemia. is a cell cycle kinase inhibitor of polo-like kinases 1, 2 and 3. Volasertib inhibits cancer growth by disrupting cell division and inducing cell death. Volasertib is administered as a 350mg one hour intravenous (IV) infusion on days 1 and 15 of a 28 day cycle in combination with low-dose cytarabine (LDAC), administered via subcutaneous injection (SC) at 20mg twice daily on days 1-10 of a 28 day cycle.
Acute myeloid leukaemia (AML): previously untreated; patients considered ineligible for intensive remission induction therapy – first line; in combination with low-dose cytarabine
volasertib (also known as BI 6727) is a small molecule inhibitor of the PLK1 (polo-like kinase 1) protein being developed by Boehringer Ingelheim for use as an anti-cancer agent. Volasertib is the second in a novel class of drugs called dihydropteridinone derivatives.
Health Canada approves NEUPRO (Rotigotine) patch for treatment of Parkinson’s disease and Restless Legs Syndrome
Rotigotine
Novel dosage form represents new treatment for Parkinson’s with efficacy in motor symptoms of the disease
April 2,2013
UCB Canada Inc. announced today that Health Canada has approved NEUPRO® (rotigotine), the first and only non-ergolinic dopamine agonist available in a patch, to treat the signs and symptoms of idiopathic Parkinson’s disease (PD) and moderate-to-severe idiopathic restless legs syndrome (RLS), also known as Willis-Ekbom disease, in adults.
NEUPRO® is the first new treatment for Parkinson’s disease approved by Health Canada in five years and provides 24-hour delivery of rotigotine through the skin into the blood stream. NEUPRO® has demonstrated efficacy in managing motor symptoms associated with Parkinson’s disease.
“The ability to ensure a steady 24-hour delivery of medication with NEUPRO® may help to reduce debilitating on and off symptoms which many patients experience with Parkinson’s treatments,” says Dr. David Grimes, Director, Parkinson’s Disease and Movement Disorders Clinic at the Ottawa Hospital. “The impact of sustained symptom control in the morning and in the evening can have a substantial effect on a patient’s quality of life.”
UCB Canada Inc. is undertaking all measures required to supply the Canadian market with NEUPRO.
“Parkinson Society Canada is pleased to learn that Canadians living with Parkinson’s now have another treatment option to help manage the symptoms of this chronic disease,” says Joyce Gordon, President and CEO, Parkinson Society Canada. “With innovative therapies such as NEUPRO® and ongoing research into the causes of this disease, we will help to ensure a brighter future and better quality of life for Canadians living with Parkinson’s.”
Although the precise mechanisms of action of NEUPRO® as treatment for PD and RLS are unknown, as a PD treatment, the mechanism of action is thought to be related to increasing the activities of the dopamine receptors within the caudate-putamen, the region of the brain that regulates movement. Similarly, in RLS, the mechanism of action of NEUPRO® is thought to be related to its ability to stimulate dopamine receptors.
Data Demonstrated Significant Symptom Improvement for PD and RLS
The effectiveness of NEUPRO® (rotigotine) in the treatment of Parkinson’s disease was evaluated in a multinational drug development program consisting of four randomized, double-blind placebo-controlled phase 3 trials. A total of seven Canadian trial sites were involved in the international studies. In all trials, patients underwent a weekly titration of NEUPRO® in 2 mg/24 hour increments to the assigned or optimal dose.
In two trials, statistically significant improvements in the combined scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) were observed in early-stage PD patients receiving NEUPRO® compared to patients receiving placebo. The UPDRS is a validated multi-item rating scale intended to evaluate mentation (mental activity), activities of daily living (ADL), motor performance, and complications of therapy. The two trials measured only the ADL and motor performance sections of the UPDRS. The UPDRS contains 13 questions relating to ADL, such as speech, dressing, and cutting food with utensils, and 27 questions related to the cardinal motor symptoms in PD patients—i.e., tremor, rigidity, bradykinesia, and postural instability.
Two trials of NEUPRO® in patients with advanced-stage PD examined change from baseline in “off” time, periods when the effectiveness of medication wears off and PD symptoms return. Statistically significant changes in off-times were observed in advanced-stage PD patients receiving NEUPRO® compared with those who received placebo.
The effectiveness of NEUPRO® in the treatment of Restless Legs Syndrome (RLS) was evaluated in two fixed-dose, randomized, double-blind, placebo-controlled phase 3 trials with maintenance periods of 6 months duration. Patients received NEUPRO® doses ranging from 0.5 mg/24 hours to 3 mg/24 hours, or placebo, once daily. Statistically significant improvements in sum scores on the International RLS Rating Scale (IRLS Scale) and the Clinical Global Impression – Improvement (CGI-I) assessment were observed in RLS patients receiving NEUPRO® compared with those receiving placebo. The IRLS Scale contains 10 items designed to assess the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence, and impact on activities of daily living and mood associated with RLS. The CGI-I is designed to clinically assess RLS symptoms on a 7-point scale.
In clinical trials, treatment emergent adverse events reported in more than 10% of patients treated with NEUPRO® for Parkinson’s disease included nausea, vomiting, dizziness, somnolence, application site reactions and headache. Treatment emergent adverse events reported in more than 10% of patients treated with NEUPRO® for Restless Legs Syndrome, included nausea, application site reactions, fatigue and headache.
About Parkinson’s disease
Parkinson’s disease (PD) is a chronic, degenerative neurological disease which affects approximately 100,000 Canadians. PD develops with the loss of nerve cells in the brain that produce a chemical called dopamine. The symptoms of PD can have an impact on many dimensions of patients’ lives. As dopamine levels fall, movement (motor) symptoms—tremors (uncontrollable shaking), rigidity (stiffness or muscle tensing) and bradykinesia (slowness and loss of spontaneous movement) — can progress, along with the underlying symptoms of PD, which are less well recognized and may be under-treated.
About Restless Legs Syndrome
Restless Legs Syndrome (RLS) is a neurological disorder characterized by unpleasant sensations in the legs and an uncontrollable urge to move to gain relief. Over 80% of people with RLS also have periodic limb movement disorder (PLMD), which causes rhythmic limb movements during sleep. RLS affects between three and 10 per cent of the population to some extent. Some estimates are much higher because RLS is thought to be underdiagnosed, and in some cases, misdiagnosed. Most people with RLS have difficulty falling asleep and staying asleep. Daytime symptoms of RLS, such as inability to sit still and involuntary leg jerks, are increasingly recognized. While the underlying pathophysiology of RLS is not fully understood, it is thought to involve central dopamine systems. Recent neuroimaging data suggest that RLS patients may carry an abnormality in dopamine transport that can be visualized both day and night. RLS can cause exhaustion and daytime fatigue, and may affect work and personal relationships. Patients with moderate-to-severe RLS are often unable to concentrate, have impaired memory, or fail to accomplish daily tasks. These patients may require long-term treatment for their RLS symptoms.
About UCB Canada Inc.
Inspired by patients and driven by science, UCB Canada Inc. is a biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe auto-immune and central nervous system diseases. For more information, please consult www.ucb.com/worldwide/canada.
Rotigotine (Neupro) is a dopamine agonist of the non-ergoline class of medications indicated for the treatment of Parkinson’s disease (PD) and restless legs syndrome (RLS) in Europe and the United States. It is formulated as a once-daily transdermal patchwhich provides a slow and constant supply of the drug over the course of 24 hours.
Like other dopamine agonists, rotigotine has been shown to possess antidepressanteffects and may be useful in the treatment of depression as well.
Rotigotine was developed by Aderis Pharmaceuticals. In 1998, Aderis licensed worldwide development and commercialization rights for rotigotine to the German pharmaceutical company Schwarz Pharma (today a subsidiary of the Belgian company UCB S.A.).
The drug has been approved by the EMEA for use in Europe in 2006 and is today being sold in several European countries. In 2007, the Neupro patch was approved by the Food and Drug Administration (FDA) as the first transdermal treatment of Parkinson’s disease in the United States. However, as of 2008, Schwarz Pharma has recalled all Neupro patches in the United States and some in Europe because of problems with the delivery mechanism. The patch was reformulated, and was reintroduced in the United States in 2012.
Rotigotine has been authorized as a treatment for restless legs syndrome since August 2008.
Rotigotine is analogous to 7-OH-DPAT and UH-232, all three of which are aminotetralinderivatives. These compounds are similar in structure to dopamine, likely underlying theirpharmacology.
Cusack, N. J.; Peck, J. V.; Drugs Future 1993, 18, 1005.
FDA Approves Tris Pharma’s New Drug Application for Karbinal ER
Carbinoxamine Maleate
2-[p-Chloro-a-[2-(dimethylamino)ethoxy]benzyl]pyridine maleate (1:1) [3505-38-2].
April 3, 2013
Tris Pharma, a specialty pharmaceutical company focused on developing innovative drug delivery technologies, today announced that the U.S. Food and Drug Administration (FDA) has approved its New Drug Application (NDA) for Karbinal ER (carbinoxamine maleate) Extended-release Oral Suspension 4mg/5mL, the first sustained-release histamine receptor blocking agent indicated for the treatment of seasonal and perennial allergic rhinitis in children ages 2 and up.
“Karbinal ER is dosed only once every 12 hours, making it an attractive treatment option for the millions of allergy sufferers who don’t respond to second-generation antihistamines and aren’t satisfied with the cumbersome dosing schedules associated with the first-generation antihistamines,” said Ketan Mehta, founder, President, and CEO of Tris Pharma. “The approval of Karbinal ER marks our fourth liquid extended-release NDA approval based upon our proprietary OralXR+ technology. We are in the process of finalizing our marketing partner and plan to launch later this year in anticipation of the fall allergy season.”
Based on physician interviews approximately 30 percent of patients don’t get adequate relief from the non-sedating antihistamines. Carbinoxamine is a mildly-sedating antihistamine with years of proven safety and efficacy. Prior to 2006, carbinoxamine was widely used, with dozens of carbinoxamine-containing combination products including extended-release solid-dose products. However, nearly all of these were older products that hadn’t gone through the FDA’s rigorous approval process. Following the Drug Efficacy Study Implementation (DESI) review, the FDA removed all unapproved products with the exception of two immediate-release formulations, creating a void for patients and doctors who valued the benefits associated with an extended-release formulation.
Dr. Laura Garabedian, a New York-based pediatrician, said, “While I’ve always found carbinoxamine to be an effective option for treating the symptoms of allergies in children, the existing immediate-release formulations of carbinoxamine require dosing multiple times a day. This is especially inconvenient for children who are in school. Now, with the approval of Karbinal ER, I look forward to having an effective and great-tasting extended-release liquid formulation to offer patients as young as two years old.”
Karbinal ER Extended-release Oral Suspension is an H1 receptor antagonist indicated for the symptomatic treatment of:
- Seasonal and perennial allergic rhinitis
- Vasomotor rhinitis
- Allergic conjunctivitis due to inhalant allergens and foods
- Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
- Dermatographism
- As therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled
- Amelioration of the severity of allergic reactions to blood or plasma
Tris Pharma is a specialty pharmaceutical company focused on the research and development of technologies-driven products. Tris has pioneered the delivery of sustained release in the liquid, chewable/ODT and strip dosage forms so patients do not have to swallow a pill. Tris’ Nobuse™ technology provides abuse deterrence for opioids and other abuse-prone drugs. Tris’ R&D and manufacturing facilities are located in Monmouth Junction, New Jersey, U.S.A. For more information, please visit http://www.trispharma.com.
Genmab: Daratumumab Granted Fast Track Designation By FDA
Monoclonal antibody
2/4/2013
Genmab A/S announced that the US Food and Drug Administration has granted Fast Track designation for daratumumab. This designation covers patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or are double refractory to a PI and an IMiD.
In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop and commercialize daratumumab.
A general representation of the method used to produce monoclonal antibodies.
Daratumumab is an investigational anti-cancer drug. It binds to CD38.[1] Daratumumab was originally developed by Genmab, but it is now being jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, which acquired worldwide commercialization rights to the drug from Genmab.[2]
Encouraging preliminary results were reported in June 2012 from a Phase 1/2 clinical trial in relapsed multiple myeloma patients.[3] Updated trial results presented in December 2012 indicate daratumumab is continuing to show promising single-agent anti-myeloma activity.[4]
- World Health Organization (2009). “International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 101” (PDF). WHO Drug Information 23 (2).
- “‘Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab'”. Janssen Biotech. Retrieved 2013-01-31.
- “ASCO: Drug Shows Promise in Myeloma”. MedPage Today.
- “‘Daratumumab Continues To Show Promise For Relapsed/Refractory Myeloma Patients (ASH 2012)'”. The Myeloma Beacon. Retrieved 2013-01-31.
AYURVEDA SPOTLIGHT- ASHWAGANDHA, THE STRESS BUSTER
Withania somnifera, also known as ashwagandha, Indian ginseng, poison gooseberry, or winter cherry, is a plant in the Solanaceae or nightshade family. Several other species in the genus Withania are morphologically similar. It is used as a herb inAyurvedic medicine.
| Ashwagandha root is known as “Indian Ginseng”. In Ayurvedic medicine it is considered an adaptogen that facilitates learning and memory. |
It grows as a short shrub (35–75 cm) with a central stem from which branches extend radially in a star pattern (stellate) and covered with a dense matte of wooly hairs (tomentose). The flowers are small and green, while the ripe fruit is orange-red and has milk-coagulating properties. The plant’s long, brown, tuberous roots are used for medicinal purposes.
Ashwagandha in Sanskrit means “horse’s smell” (ashwa– horse, gandha– smell), probably originating from the odour of its root which resembles that of a sweaty horse.
The species name somnifera means “sleep-inducing” in Latin
Cultivation
Ashwagandha plant with berries
Withania somnifera is cultivated in many of the drier regions of India, such as Mandsaur Districtof Madhya Pradesh, Punjab, Sindh, Gujarat,and Rajasthan.It is also found in Nepal
Withania somnifera is grown as late rainy-season (kharif) crop. Semitropical areas receiving 500 to 750 mm rainfall are suitable for its cultivation as a rainfed crop. If one or two winter rains are received, then root development improves.
The crop requires a relatively dry season during its growing period. It can tolerate a temperature range of 20 to 38°C and as low a temperature as 10°C. The plant grows from sea level to an altitude of 1500 meters.
Ashvagandha plant at Talkatora Gardens, Delhi
Withania somnifera is prone to several pests and diseases. Leaf spot disease caused byAlternaria alternata is the most prevalent disease, which is most severe in the plains ofPunjab, Haryana, and Himachal Pradesh. Biodeterioration of its pharmaceutically active components during leaf spot disease has been reported. The Choanephora cucurbitarumcauses a stem and leaf rot of Withania somnifera Oxyrachis tarandus (atreehopper/cowbug species) feeds on the apical portions of the stem, making them rough and woody in appearance and brown in colour. The apical leaves are shed and the plant gradually dies away. Carmine red spider mite (Tetranychus urticae) is the most prevalent pest of Withania somnifera in India.
The berries can be used as a substitute for rennet, to coagulate milk in cheese-making
The main chemical constituents are alkaloids and steroidal lactones. These include tropineand cuscohygrine. The leaves contain the steroidal lactones, withanolides, notably withaferin A, which was the first withanolide to be isolated from W. somnifera.
Traditional medicinal uses
In Ayurveda, the berries and leaves of W. somnifera are locally applied to tumors, tubercular glands, carbuncles, and ulcers.[5] The roots of W. somnifera are used to prepare the herbal remedy ashwagandha, which has been traditionally used to treat various symptoms and conditions.
Side effects
In two published clinical trials of W. somnifera, the side effects were not significantly different from those experienced by placebo-treated individuals.
Ashwagandha Scientific Research
Ashwagandha contains many useful medicinal chemicals, including withanolides, (steroidal lactones), alkaloids, choline, fatty acids, amino acids, and a variety of sugars. While the leaves and fruit have valuable therapeutic properties, the root of the ashwagandha plant is the part most commonly used in Western herbal remedies.
Medical researchers have been studying ashwagandha with great interest and as of this date have carried out 216 studies of its healing benefits, summarized below:
- confers immune system protection
- combats the effects of stress
- improves learning, memory, and reaction time
- reduces anxiety and depression without causing drowsiness
- stabilizes blood sugar
- lowers cholesterol
- reduces brain-cell degeneration
- contains anti-malarial properties
- offers anti-inflammatory benefits
Some studies have also found that ashwagandha inhibits the growth of cancer cells in small animals, but further research is needed to determine whether the herb prevents the development of tumors in human beings.
Ashwagandha in particular is known for its ability to calm, and some research indicates this herb can be used to promote sleep. In Texas, researchers noted the similarities in the sleep-inducing properties of ashwagandha and the calming effects of the well-known amino acid GABA. Likewise, ashwagandha has also been shown to ease anxiety or restlessness, as well as to reduce the symptoms of drug withdrawal. Its ability to stabilize moods and encourage adrenal recovery is highly valued by many herbalists.
But the benefits of ashwagandha extend far beyond mood. In India it is also used to help older patients with mental agility, cognitive ability, and memory. It is also known for its ability to fight off cold and cough symptoms. Preliminary studies give researchers reason to feel that ashwagandha also has the potential ability to decrease cancer cells without adversely affecting healthy cells.
Ashwagandha Practical and Precautions
The usual recommended dose is 600 to 1000 mg, twice daily. For people who suffer from insomnia and anxiety, having a cup of hot milk that contains a teaspoon of powdered ashwagandha before bedtime is beneficial. In extremely large doses, ashwagandha has been reported to induce abortions in animals. Although no similar studies have been carried out on humans, women should avoid the herb during pregnancy.You should consult your ayurvedic doctor or other health care professional before starting on any ayurveda treatment.
Other Name:
Ajagandha, Amangura, Amukkirag, Asan, Asana, Asgand, Asgandh, Asgandha, Ashagandha, Ashvagandha, Ashwaganda, Ashwanga, Asoda, Asundha, Asvagandha, Aswagandha, Avarada, Ayurvedic Ginseng, Cerise d’Hiver, Clustered Wintercherry, Ghoda Asoda, Ginseng Ayurvédique, Ginseng Indien, Hayahvaya, Indian Ginseng, Kanaje Hindi, Kuthmithi, Orovale, Peyette, Physalis somnifera, Samm Al Ferakh, Samm Al Rerakh, Sogade-Beru, Strychnos, Turangi-Ghanda, Vajigandha, Winter Cherry, Withania, Withania somnifera.
Drug spotlight-Raloxifene
Raloxifene
Raloxifene: The FDA approved Raloxifene to reduce the risk of invasive breast cancer in postmenopausal women in 2007. It was initially developed to treat osteoporosis.
| Identifiers | |
|---|---|
| CAS number | 84449-90-1 |
Raloxifene (marketed as Evista by Eli Lilly and Company) is an oral selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. It is used in the prevention of osteoporosis in postmenopausal women.
In 2006, the National Cancer Institute announced that raloxifene was as effective astamoxifen in reducing the incidence of breast cancer in postmenopausal women at increased risk. A major adverse effect of tamoxifen is uterine cancer; raloxifene had fewer uterine cancers. Tamoxifen increased the risk of cataracts, but raloxifene did not. Both groups had more blood clots in veins and the lungs, but that side effect was more common with tamoxifen than raloxifene.[2][3][4] On September 14, 2007, the U.S. Food and Drug Administration announced approval of raloxifene for reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer.[5]
An editorial in Lancet Oncology criticized the way that information about the drug was released.[6]
Raloxifene hydrochloride (HCl) has the empirical formula C28H27NO4S•HCl, which corresponds to a molecular weight of 510.05 g/mol. Raloxifene HCl is an off-white to pale-yellow solid that is slightly soluble in water.
SERMs mimic estrogen in some tissues and have anti-estrogen activity in others. Other SERMs, such as Pfizer’s lasofoxifene and Wyeth’s bazedoxifene are in the later development phases.
Raloxifene is indicated for the treatment and prevention of osteoporosis in postmenopausalwomen, for reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. For either osteoporosis treatment or prevention, supplemental calciumand/or vitamin D should be added to the diet if daily intake is inadequate.
Raloxifene is contraindicated in lactating women or women who are or may becomepregnant, in women with active or past history of venous thromboembolic events, includingdeep vein thrombosis, pulmonary embolism, and retinal vein thrombosis and in women known to be hypersensitive to raloxifene.
Common adverse events considered to be drug-related were hot flashes and leg cramps.
Raloxifene may infrequently cause serious blood clots to form in the legs, lungs, or eyes. Other reactions experienced include leg swelling/pain, trouble breathing, chest pain, vision changes. Raloxifene is a teratogenic drug, i.e., can cause developmental abnormalities such as birth defects.
In a 2006 study published in New England Journal of Medicine, raloxifene produced significantly more strokes and blood clots than the placebo.[7]
A report in September 2009 from Health and Human Services’ Agency for Healthcare Research and Quality suggests that tamoxifen and raloxifene, used to treat breast cancer significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.[8]
As cancer drug
Bottle of Raloxifene
Raloxifene reduces the risk of hormone-positive breast cancer and vertebral fractures “without a shadow of a doubt,” but its effects on cardiovascular disease remain less certain, according to the results of the “Raloxifene for Use of the Heart” (RUTH) study published in the July 13, 2006 issue of the New England Journal of Medicine by Dr. Elizabeth Barrett-Connor (University of California at San Diego) and colleagues.[9]
In the trial, in women with coronary heart disease (CHD) or multiple risk factors for CHD, raloxifene had no significant effect on the primary end point, coronary events, but it did significantly increase the risk of venous thromboembolism (VTE). And although the drug had no effect on stroke, there was a seemingly paradoxical significant increase in death from stroke.[10]
On September 14, 2007, Steven K. Galson, the director of the United States Food and Drug Administration’s Center for Drug Evaluation and Research announced authorization of the sale of raloxifene to prevent invasive breast cancer in post-menopausal women.[11]
Chemical synthesis
Jones, Charles D.; Jevnikar, Mary G.; Pike, Andrew J.; Peters, Mary K.; Black, Larry J.; Thompson, Allen R.; Falcone, Julie F.; Clemens, James A. (1984). “Antiestrogens. 2. Structure-activity studies in a series of 3-aroyl-2-arylbenzo[b]thiophene derivatives leading to [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl]-[4-[2-(1-piperidinyl)ethoxy]phenyl]methanone hydrochloride (LY 156758), a remarkably effective estrogen antagonist with only minimal intrinsic estrogenicity”. Journal of Medicinal Chemistry 27 (8): 1057–66.doi:10.1021/jm00374a021. PMID 6431104.
- Jeong, Eun Ju; Liu, Yong; Lin, Huimin; Hu, Ming (2005-03-15). “Species- and Disposition Model-Dependent Metabolism of Raloxifene in Gut and Liver: Role of UGT1A10”. Drug Metabolism and Disposition ( ASPET) 33 (6): 785–794. doi:10.1124/dmd.104.001883.PMID 15769887. Retrieved 2010-10-20.
- Study of Tamoxifen and Raloxifene (STAR) Trial Cancer.gov
- Results of the Study of Tamoxifen and Raloxifene (STAR) Released: Osteoporosis Drug Raloxifene Shown to be as Effective as Tamoxifen in Preventing Invasive Breast Cancer (Press Release) 06/21/2006
- Vogel, Victor; Joseph Constantino, Lawrence Wickerman et al. (2006-06-21). “Effects of Tamoxifen vs. Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes”. The Journal of the American Medical Association 295 (23): 2727–2741. doi:10.1001/jama.295.23.joc60074. PMID 16754727.
- “FDA Approves New Uses for Evista” (Press release). U.S. Food and Drug Administration. 2007-09-14. Retrieved 2007-09-15.
- Thelancetoncology, (2006). “A STARring role for raloxifene?”. Lancet Oncol 7 (6): 443. doi:10.1016/S1470-2045(06)70701-X.PMID 16750489.
- 355:125-137 July 13, 2006, Effects of Raloxifene on Cardiovascular Events and Breast Cancer in Postmenopausal Women Elizabeth Barrett-Connor, Lori Mosca, Peter Collins, et al. for the Raloxifene Use for The Heart (RUTH) Trial Investigators [Free full text]
- OncoGenetics.Org (September 2009). “Medications Effective in Reducing Risk of Breast Cancer But Increase Risk of Adverse Effects”. OncoGenetics.Org. Retrieved 2009-09-14.[dead link]
- Lisa Nainggolan (July 12, 2006). A balancing act: The pro and cons of raloxefene.
- Barrett-Connor E, Mosca L, Collins P, et al. (2006-07-13). “Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women”. New England Journal of Medicine 355 (2): 125–137. doi:10.1056/NEJMoa062462. PMID 16837676.
- AFP.google.com, US approves Lilly’s Evista for breast cancer prevention
- STAR: a head-to-head comparison of tamoxifen and raloxifene as breast-cancer preventatives
- Full Prescribing Information
- Position paper of the National Women’s Health Network
- Heringa M (2003). “Review on raloxifene: profile of a selective estrogen receptor modulator”. Int J Clin Pharmacol Ther 41 (8): 331–45. PMID 12940590.
- Barrett-Connor E (2001). “Raloxifene: risks and benefits”. Ann N Y Acad Sci 949: 295–303. doi:10.1111/j.1749-6632.2001.tb04036.x. PMID 11795366.
- Raloxifene bound to proteins in the PDB
New Drug Approvals 