First mAb biosimilars backed by EMA advisors

EU Comments Off

Jul 022013

Among the latest opinions issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use, perhaps the most eye-catching are recommendations for two biosimilar versions of Johnson & Johnson’s monoclonal antibody blockbuster Remicade.

The CHMP has backed Remsima from South Korea’s Celltrion and Hospira’s Inflectra, both of which contain the same active substance as Remicade (infliximab). They have been recommended for authorisation in the same indications as the J&J drug, ie a range of autoimmune diseases such as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and and psoriasis.

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http://www.pharmatimes.com/Article/13-07-01/First_mAb_biosimilars_backed_by_EMA_advisors.aspx

FDA OKs Novartis’ Exelon Patch for Severe Alzheimer’s

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Jun 292013

Novartis Exelon® Patch now FDA approved to treat patients across all stages of Alzheimer’s disease

http://www.pharmalive.com/fda-oks-novartis-exelon-patch-for-alzheimers

Exelon Patch (rivastigmine transdermal system) contains rivastigmine, a reversible cholinesterase inhibitor known chemically as (S)- 3-[1-(dimethylamino) ethyl]phenyl ethylmethylcarbamate. It has an empirical formula of C₁₄H₂₂N₂O₂ as the base and a molecular weight of 250.34 (as the base). Rivastigmine is a viscous, clear, and colorless to yellow to very slightly brown liquid that is sparingly soluble in water and very soluble in ethanol, acetonitrile, n-octanol and ethyl acetate.

The distribution coefficient at 37°C in n-octanol/phosphate buffer solution pH 7 is 4.27.

EXELON PATCH (rivastigmine) Structural Formula Illustration

Exelon Patch is for transdermal administration. The patch is a four-layer laminate containing the backing layer, drug matrix, adhesive matrix and overlapping release liner (see Figure 1). The release liner is removed and discarded prior to use.

Figure 1: Cross Section of the Exelon Patch

EXELON PATCH (rivastigm ine transdermal system) Figure 1 Illustration

Layer 1: Backing Film
Layer 2: Drug Product (Acrylic) Matrix
Layer 3: Adhesive (Silicone) Matrix
Layer 4: Release Liner (removed at time of use)

Excipients within the formulation include acrylic copolymer, poly(butylmethacrylate, methylmethacrylate), silicone adhesive applied to a flexible polymer backing film, silicone oil, and vitamin E.

Navidea starts clinical trial for Alzheimer’s diagnostic drug

Phase 3 drug Comments Off

Jun 282013

Navidea Biopharmaceuticals hopes to bring an early diagnostic drug for Alzheimer’s disease to market.

AZD4694, NAV4694 STRUCTURE

Navidea starts clinical trial for Alzheimer’s diagnostic drug
Business First of Columbus
The Phase 3 trial for the Alzheimer’s agent, at the moment named NAV4694, will compare how well the drug displays the buildup of a damaging protein in the brain of patients believed to have Alzheimer’s compared with what’s found in the autopsy. There …

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http://www.bizjournals.com/columbus/news/2013/06/27/navidea-starts-clinical-trial-for.html

http://jnm.snmjournals.org/content/54/6/880.abstract

Navidea Biopharmaceuticals, a Dublin, Ohio biopharmaceutical company focused on precision diagnostics, earlier this week announced the completion of a study of its novel radiopharmaceutical NAV4694 as a biomarker for Alzheimer’s disease (AD).

NAV4694 is designed to aid visual detection and quantification of cerebral beta amyloid in diagnosing Alzheimer’s disease (AD). One hallmark of AD is the accumulation of beta amyloid plaques between nerve cells in the brain.

The study was designed and conducted by Navidea’s partner, AstraZeneca, to assess the safety and of the biomarker during PET scanning in subjects with AD and in healthy volunteers. Efficacy measures included binding parameters and overall image quality. The 16-patient trial was completed at Karolinska Institutet sites in Stockholm, Sweden.

DATE RAPE DRUGS-What is Rohypnol?

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Jun 272013

FLUNITRAZEPAM

Rohypnol

What is Rohypnol?

“Roofies.” Sounds like a cartoon character or a piece of candy. However, nothing could be further from the truth about Roofies, also known as the drug Rohypnol.Rohypnol (Flunitrazepam) is a type of benzodiazepine, a class of drugs that depresses the central nervous system. You may have heard of Valium and Xanax. These are also benzodiazepines used as sedatives and antianxiety agents. Rohypnol was developed as a sleeping aid. It is also used in therapy settings to relax patients and to get them talking. Rohypnol is manufactured in Europe and Latin American and is sold in many countries around the world. However, it is illegal in the United States and Canada. The pills are round, white and smaller than aspirin.

Because Rohypnol is inexpensive, it is becoming popular with high school and college students. In the US, Rohypnol is used mostly at parties, and usually taken with alcohol. It has a synergistic effect with other drugs such as alcohol. This means that one drug increases the effect of the other.

Rohypnol Tablets

Image courtesy of the
U.S. Department of Justice

Behavioral Effects of Rohypnol

Rohypnol can produce amnesia (memory loss) and muscle relaxation and make people lower their inhibitions. An inhibition is when you feel like you can’t do something. When inhibitions are lowered, people feel as if an obstacle has been removed. Therefore, they can talk more freely and feel less shy. Because Rohypnol is colorless, odorless and flavorless, it can be slipped into drinks unnoticed. This is one reason this drug is so dangerous. People may consume it without knowing it. It dissolves quickly and takes effect in 20-30 minutes. Its effects can last 8-12 hours. Within the past few years, Rohypnol has become known as the “date rape” drug. People will come home from a party and have no idea what happened to them because they unknowingly ingested Rohypnol, passed out, and woke up several hours later with no memory of the evening. To address this new use, Congress passed the “Drug-Induced Rape Prevention and Punishment Act of 1996” to increase federal penalties for the use of any controlled substance to aid in a sexual assault.

Continued, repeated use of Rohypnol may result in addiction and although Rohypnol is a sedative, it can cause aggressive behavior in some people. Withdrawal symptoms may occur and include headaches, sore muscles, hallucinations, convulsions, and possibly seizures 1-2 weeks after quitting the drug.

Although overdoses are rarely fatal, emergency services are sometimes required because Rohypnol can cause a person to vomit, hallucinate, have trouble breathing and fall into a coma. When Rohypnol is combined with alcohol the outcome is usually worse.

Street names for Rohypnol include rophies, ruffies, R2, roofenol, Roche, la rocha, rope, roopies, ropies, and rib.

Effects of Rohypnol on the Brain

The benzodiazepines influence behavior by interacting with receptors on neurons in the brain that use the neurotransmitter called GABA. When GABA binds to receptors, it usually inhibits a neuron and acts to reduce neuronal activity. When benzodiazepines attach to GABA receptors, they increase GABA binding to other receptors. In this way, benzodiazepines enhance the effects of GABA and reduce brain activity.The fact that there are receptors for benzodiazepines in the brain suggests that the brain makes its own type of benzodiazepine. The brain has been found to make its own morphine, the endorphins, but the brain’s own benzodiazepine has not yet been discovered.

Vical and Astellas Announce Initiation of Phase 3 Trial of ASP0113 Cytomegalovirus Vaccine

VACCINE Comments Off

Jun 272013

Illustration of the CMV life cycle from viral entry to egress of new infectious virions.

Jun 25, 2013, Vical Incorporated and Astellas Pharma Inc. today announced the initiation of a multinational Phase 3 registration trial of ASP0113 (TransVax(TM)), in approximately 500 hematopoietic cell transplant (HCT) recipients. Vical and Astellas entered into exclusive worldwide license agreements in 2011 to develop and commercialize ASP0113, Vical’s investigational therapeutic vaccine designed to control cytomegalovirus (CMV) in transplant recipients. Astellas is conducting the trial, and Vical is providing development, regulatory and manufacturing support. The companies expect to begin a separate Phase 2 trial of ASP0113 in solid organ transplant (SOT) recipients later this year.

http://www.marketwatch.com/story/vical-and-astellas-announce-initiation-of-phase-3-trial-of-asp0113-cytomegalovirus-vaccine-2013-06-25

About ASP0113

ASP0113 is an investigational bivalent DNA vaccine containing plasmids (closed loops of DNA) encoding human CMV pp65 and gB antigens for induction of both cellular and humoral immune responses. ASP0113 is formulated with a proprietary poloxamer-based delivery system. ASP0113 has received orphan drug designation in the United States and Europe for HCT and SOT patients.

About CMV

CMV is a herpes virus that infects more than half of all adults in the United States by age 40, and is even more widespread in developing countries. A healthy immune system typically protects an infected person against CMV disease, but does not prevent or clear latent infection, and those whose immune systems are not fully functional are at high risk of CMV reactivation, potentially leading to severe illness or death. Those at greatest risk include transplant patients and infants born to mothers who first become infected during pregnancy. Vical is pursuing two distinct vaccine approaches for these separate market segments: ASP0113 for the transplant market and CyMVectin(TM) for the congenital disease market.

About Astellas

Astellas Pharma Inc., located in Tokyo, Japan, is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. Astellas has approximately 17,000 employees worldwide. The organization is committed to becoming a global category leader in Urology, Immunology (including Transplantation) and Infectious diseases, Oncology, Neuroscience and DM Complications and Kidney diseases. For more information on Astellas Pharma Inc., please visit www.astellas.com/en.

About Vical

Vical researches and develops biopharmaceutical products based on its patented DNA delivery technologies for the prevention and treatment of serious or life-threatening diseases. Potential applications of the company’s DNA delivery technology include DNA vaccines for infectious diseases or cancer, in which the expressed protein is an immunogen; cancer immunotherapeutics, in which the expressed protein is an immune system stimulant; and cardiovascular therapies, in which the expressed protein is an angiogenic growth factor. The company is developing certain infectious disease vaccines and cancer therapeutics internally. In addition, the company collaborates with major pharmaceutical companies and biotechnology companies that give it access to complementary technologies or greater resources. These strategic partnerships provide the company with mutually beneficial opportunities to expand its product pipeline and address significant unmet medical needs. Additional information on Vical is available at www.vical.com.

New Fycompa® (perampanel) Data Presented at International Epilepsy Congress (IEC)

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Jun 272013

PERAMPANEL

New data provides additional evidence for use of Fycompa in partial-onset epilepsy

HATFIELD, England, June 26, 2013 /CNW/ – New data from 11 abstracts, including two oral presentations, presented at the 30^th International Epilepsy Congress (IEC) in Montreal, Canada provide additional data on the safety, efficacy and impact on quality of life (QOL) of once daily Fycompa^® (perampanel) as adjunct treatment in partial-onset epilepsy, the most common form of seizures.

http://www.newswire.ca/en/story/1190177/new-fycompa-perampanel-data-presented-at-international-epilepsy-congress-iec

Perampanel (trade name Fycompa) is an antiepileptic drug developed byEisai Co. that acts as a selective noncompetitive antagonist of AMPA receptors, the major subtype of ionotropic glutamate receptors.

Perampanel was found to be effective in the treatment of refractory partial-onset seizures in three pivotal (Phase 3) clinical trials and has been approved for marketing under the brand name Fycompa by the European Medicines Agency. The minimum effective dose is 4 mg once daily; doses of 8 mg and 12 mg daily provide a greater therapeutic benefit with a corresponding increase in adverse events. Dizziness and somnolence/sedation/fatigue are the most frequent dose-related adverse events. The drug is currently approved, for the control of partial-onset seizures, in those of both sexes who suffer from epilepsy and who are 12 years of age and older, by the Food and Drug Administration, and is considered to be a scheduled drug (an agent with the potential for addiction). Perampanel has been studied in other clinical indications includingParkinson’s disease.

Could “Magic” Mushrooms be used to treat anxiety and depression?

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Jun 252013

Emerging research indicates that low doses of the active chemical psilocybin can have positive psychiatric effects. Image via Wikimedia Commons/Dohduhdah

The latest study, published last week in Experimental Brain Research, showed that dosing mice with a purified form of psilocybin reduced their outward signs of fear. The rodents in the study had been conditioned to associate a particular noise with the feeling of being electrically shocked, and all the mice in the experiment kept freezing in fear when the sound was played even after the shocking apparatus was turned off. Mice who were given low doses of the drug, though, stopped freezing much earlier on, indicating that they were able to disassociate the stimuli and the negative experience of pain more easily.

http://myscienceacademy.org/2013/06/12/could-magic-mushrooms-be-used-to-treat-anxiety-and-depression/

Psilocybin is a naturally occurring psychedeliccompound produced by more than 200 species of mushrooms, collectively known aspsilocybin mushrooms. The most potent are members of the genus Psilocybe, such asP. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from about a dozen other genera. As a prodrug, psilocybin is quickly converted by the body to psilocin, which has mind-altering effects similar to those of LSD, mescaline, and DMT. The effects generally include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences, and can include possible adverse reactions such as nausea and panic attacks.

Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine or 4-PO-DMT) is a prodrug that is converted into the pharmacologicallyactive compound psilocin in the body by a dephosphorylation reaction. This chemical reaction takes place under strongly acidicconditions, or under physiological conditions in the body, through the action of enzymes called phosphatases.

Psilocybin is a tryptamine compound with a chemical structure containing an indole ring linked to an ethylamine substituent. It is chemically related to the amino acid tryptophan, and is structurally similar to the neurotransmitter serotonin. Psilocybin is a member of the general class of tryptophan-based compounds that originally functioned as antioxidants in earlier life forms before assuming more complex functions in multicellular organisms, including humans. Other related indole-containing psychedelic compounds includedimethyltryptamine, found in many plant species and in trace amounts in some mammals, and bufotenine, found in the skin ofpsychoactive toads. Biosynthetically, the biochemical transformation from tryptophan to psilocybin involves several enzyme reactions: decarboxylation, methylation at the N⁹ position, 4-hydroxylation, and O-phosphorylation. Isotopic labeling experiments suggest that tryptophan decarboxylation is the initial biosynthetic step and that O-phosphorylation is the final step. The precise sequence of the intermediate enzymatic steps is not known with certainty, and the biosynthetic pathway may differ between species.

A possible biosynthetic route to psilocybin. Although the order of the first (decarboxylation) and last (phosphorylation) steps are known with some certainty, the sequence of the two intermediate steps is speculative.

New aspects of natural products in drug discovery

Uncategorized Comments Off

Jun 252013

Structures of compounds of microbial origin that are in development as anti-infective agents. Key to compounds: 1, arylomycin; 2, ECO-0501; 3, GE23077; 4, GE81112; 5, LBM415; 6, AC98–6446.

During the past 15 years, most large pharmaceutical companies have decreased the screening of natural products for drug discovery in favor of synthetic compound libraries. Main reasons for this include the incompatibility of natural product libraries with high-throughput screening and the marginal improvement in core technologies for natural product screening in the late 1980s and early 1990s. Recently, the development of new technologies has revolutionized the screening of natural products. Applying these technologies compensates for the inherent limitations of natural products and offers a unique opportunity to re-establish natural products as a major source for drug discovery. Examples of these new advances and technologies are described in this review.

http://www.sciencedirect.com/science/article/pii/S0966842X07000686

New aspects of natural products in drug discovery

Kin S. Lam

Nereus Pharmaceuticals Inc., 10480 Wateridge Circle, San Diego, CA 92121, USA

Available online 11 April 2007

http://dx.doi.org/10.1016/j.tim.2007.04.001,

Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company Announce Updates to Prescribing Information for TRADJENTA® (linagliptin) Tablets and JENTADUETO® (linagliptin and metformin hydrochloride) Tablets

Uncategorized Comments Off

Jun 232013

linagliptin

June 20, 2013 /PRNewswire/ — Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) announce the U.S. Food and Drug Administration (FDA) has approved updates to the full U.S. Prescribing Information (PI) for TRADJENTA® (linagliptin) tablets and JENTADUETO® (linagliptin and metformin hydrochloride) tablets. These updates are part of ongoing efforts to update product labels to ensure physicians, pharmacists and patients have the information they need to use our medications appropriately. Information about pancreatitis was included in the adverse reactions sections of the original labels for these products; it is now displayed in additional sections of the PIs.1,2

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http://www.pharmalive.com/tradjenta-jentadueto-get-label-updates-for-pancreatitis-risk

Linagliptin (BI-1356, trade names Tradjenta and Trajenta) is a DPP-4 inhibitordeveloped by Boehringer Ingelheim for treatment of type II diabetes.

Linagliptin (once-daily) was approved by the US FDA on 2 May 2011 for treatment of type II diabetes. It is being marketed by Boehringer Ingelheim and Lilly.

Takeda Submits Vedolizumab BLA

bla Comments Off

Jun 222013

Takeda Pharmaceuticals USA Inc. announced that a Biologics License Application (BLA) has been submitted to the United States (U.S.) Food and Drug Administration (FDA) for vedolizumab, an investigational humanized monoclonal antibody for the treatment of adults with moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC), the two most common types of inflammatory bowel disease (IBD).

http://www.dddmag.com/news/2013/06/takeda-submits-vedolizumab-bla

Vedolizumab is a monoclonal antibody being developed by Millennium Pharmaceuticals, Inc. for the treatment of ulcerative colitis and Crohn’s disease. It binds to integrin α₄β₇ (LPAM-1, lymphocyte Peyer’s patch adhesion molecule 1).

The cell line was discovered by Dr. Andrew Lazarovits and Dr. Robert Colvin as the murine MLN0002 homologue. Their discovery of the mouse equivalent of this antibody—originally applied to anti-rejection strategies in kidney transplantation—was published in the journal Nature, in 1996. The research was conducted at Massachusetts General Hospital in Boston, MA. Dr. Lazarovits and Dr. Colvin’s cell line was subsequently licensed to Millennium Pharmaceuticals of Boston for further development.