DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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TLC388 (Lipotecan®) Taiwan Liposome Company Hepatic cancer drug candidate gets fast track approval status from SFDA
TLC388 (Lipotecan®) structure can be figured out from a link below of a poster
http://www.tlcbio.com/files/news/2011111701580783.pdf
IT IS A CAMPOTHECIN ANALOGUE
The str can be concluded from above picture from a poster by TLC BIO
TLC388 (Lipotecan) is a potent Topoisomerase-1 inhibitor and it can disrupt both Sonic Hedgehog and HIF1-α pathways to overcome cancer drug resistance and inhibit angiogenesis induced by tumor hypoxia. This phase I first-in-human study of Lipotecan examined the MTD, safety, anti-tumor activity and pharmacokinetic profiles of TLC388 in patients with advanced incurable solid tumors.
Methods: Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle. Patients underwent safety assessments regularly and tumor assessments every other cycle. Pharmacokinetic samples were drawn on days 1, 8 and 15 of cycles 1 and 2 for all treated patients.
http://mct.aacrjournals.org/cgi/content/meeting_abstract/10/11_MeetingAbstracts/A89
http://clinicaltrials.gov/show/NCT00747474
MAR19 2013
China SFDA has granted fast track approval status to Taiwan Liposome company hepatic cancer drug Lipotecan, shortening the review period. The drug will enter Phase 2 clinical trials in China in the second half of this year. Lipotecan has been granted orphan drug status by US FDA and EU EMEA for the treatment of hepatocellular carcinoma (HCC)
Nexavar is the standard of care in first line advanced liver cancer patients. Lipotecan as a second-line treatment allows patients who have failed prior treatment with Nexavar to maintain a six month course of the disease without progressing
ELQ-300, Promising new antimalarial to enter clinical testing phase
ELQ-300
6-chloro-7-methoxy-2-methyl-3-{4-[4-(trifluoromethoxy)phenoxy]phenyl}quinolin-4(1H)-one
21 MAR 2013
A promising new antimalarial drug with the potential to cure and block transmission of the mosquito-borne disease has been discovered by researchers.
The drug, known as ELQ-300, has demonstrated preventative transmission-blocking and a low likelihood of developing rapid resistance to major strains of malaria parasites.
Researchers say it is also likely that the drug could be produced more cheaply than existing antimalarials.
ELQ-300 is now moving into clinical testing.
This new treatment was developed by the Medicines for Malaria Venture (MMV) drug discovery initiative, which is made up of researchers from Oregon Health & Science University in Portland, Drexel University in Philadelphia, University of South Florida and Monash University in Australia.
The full details of their research was published yesterday in the Science Translational Medicine journal.
During the process of creating the drug, researchers discovered and developed a series of potent compounds to combat malaria quinolones.
From this series, they narrowed down the most effective drug candidates to one lead drug, ELQ-300.
“This is one of the first drugs ever to kill the malaria parasite in all three stages of its life cycle,” said Dr Kyle, a member of the Global Infectious Diseases Research team at the USF College of Public Health.
“So, it may become part of a new-generation therapy that not only treats sick people and prevents them from getting ill, but also blocks the transmission of malaria from mosquitoes to humans … If the drug can break the parasite life cycle, we may ultimately eradicate the disease.”
Malaria is a tropical disease that kills nearly one million people a year, mostly in developing countries.
ELQ-300 was derived from the first antimalarial quinolone, endochin, discovered more than 60 years ago but never pursued as a treatment because it appeared not to work in humans.
Researchers used new technology to develop this latest class of drug.
“This was a very challenging project requiring years of hard work, collaboration across disciplines, and a good portion of luck,” said Dr. Manetsch, from the University of South Florida.
ELQ-300 is an experimental antimalarial medication. It is an endochin-like quinolone and the first in a new class of antimalarials known as quinolone-3-diarylethers.[1]
ELQ-300 acts as an inhibitor of the mitochondrial cytochrome bc1 complex (complex III in the electron transport chain).[1] In preclinical studies with mice, it was found to be highly active against Plasmodium falciparum and Plasmodium vivax at all life cycle stages that play a role in the transmission of malaria, and to have good oral bioavailability.[1]
- Nilsen A et al (2013). “Quinolone-3-diarylethers: a new class of antimalarial drug”.Science Translational Medicine 5 (177): 177ra37. doi:10.1126/scitranslmed.3005029.ISSN 1946-6234.
- “NIH-Supported Researchers Identify New Class of Malaria Compounds” (Press release). U.S. National Institutes of Health. March 20, 2013.
- A Nilsen et al, Sci. Transl. Med., 2013, DOI:10.1126/scitranslmed.3005029
- ‘ELQ-300 targets the parasite mitochondrion,’ Riscoe says. In most organisms, the primary function of the mitochondria is to produce energy by making adenosine triphosphate (ATP). ‘But in the parasite, the primary function is to produce the pyrimidine building blocks for DNA [thymine and cytosine].’ The molecule prevents the synthesis of those bases, which prevents the parasite from reproducing, so it dies.
FDA Approves Dotarem, a New Magnetic Resonance Imaging Agent
| Cas No. | 98059-18-8 |
| Name | 2-[4,7-bis(carboxylatomethyl)-10-(carboxymethyl)-1,4,7, 10-tetrazacyclododec-1-yl]acetate; gadolinium(3+); (2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentol |
March 20, 2013 — The U.S. Food and Drug Administration today approved Dotarem (gadoterate meglumine) for use in magnetic resonance imaging (MRI) of the brain, spine and associated tissues of patients ages 2 years and older.
Dotarem is a gadolinium-based contrast agent (GBCA) that helps radiologists see abnormalities on images of the central nervous system (CNS), the part of the body that contains the brain and spine, and surrounding tissues.
“Dotarem was shown to be a safe and effective magnetic resonance imaging agent in patients ages 2 years and older,” said Dwaine Rieves, M.D., director of the Division of Medical Imaging Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval provides doctors with another option to help evaluate anatomic abnormalities within the central nervous system.”
Dotarem (gadoterate meglumine)
Company: Guerbet
Treatment for: Diagnostic
Dotarem (gadoterate meglumine) is a gadolinium-based contrast agent under review for use in magnetic resonance imaging (MRI).
Dotarem is the only macrocyclic and ionic gadolinium-based contrast agent (GBCA) for the intravenous use with magnetic resonance imaging (MRI) in the brain (intracranial), spine and associated tissues in adults and pediatric patients to detect and visualize areas with disruption of the blood-brain barrier (BBB) and/or abnormal vascularity. The Guerbet NDA recommended dose is 0.1 mmol Gd/kg.
Gadoteric acid
Gadoteric acid (trade names Artirem, Dotarem) is a macrocycle-structured gadolinium-based MRI contrast agent. It consists of the organic acid DOTA as a chelating agent, and gadolinium (Gd3+), and is used in form of the meglumine salt.[1] The drug is approved and used in a number of countries worldwide.[2]
- Herborn, C. U.; Honold, E.; Wolf, M.; Kemper, J.; Kinner, S.; Adam, G.; Barkhausen, J. (2007). “Clinical Safety and Diagnostic Value of the Gadolinium Chelate Gadoterate Meglumine (Gd-DOTA)”. Investigative Radiology 42 (1): 58–62. doi:10.1097/01.rli.0000248893.01067.e5. PMID 17213750. edit
- Drugs.com: Gadoteric Acid
A gadolinium chelate paramagnetic contrast agent. When placed in a magnetic field, gadoterate meglumine produces a large magnetic moment and so a large local magnetic field, which can enhance the relaxation rate of nearby protons; as a result, the signal intensity of tissue images observed with magnetic resonance imaging (MRI) may be enhanced. Because this agent is preferentially taken up by normal functioning hepatocytes, normal hepatic tissue is enhanced with MRI while tumor tissue is unenhanced. In addition, because gadobenate dimeglumine is excreted in the bile, it may be used to visualize the biliary system using MRI.
TheraVida Presents Positive Phase 2 Data for Tolenix (THVD-201) in Patients with Overactive Bladder
mar18, 2013
TheraVida, Inc., a clinical-stage biopharmaceutical company developing novel combination drug products, presented positive results from a Phase 2 clinical trial of its lead product candidate, Tolenix ™ (THVD-201), for the treatment of overactive bladder (OAB) and urge urinary incontinence (UUI) at the 28 th Annual Congress of the European Urological Association (EAU) in Milan, Italy.
Tolenix ™ is a twice-daily (BID) proprietary combination of tolterodine, to treat OAB and UUI, and pilocarpine, to reduce the significant dry mouth (xerostomia) caused by muscarinic antagonist medications such as tolterodine.
tolterodine
pilocarpine
The objectives of the randomized, double-blinded, multiple-crossover Phase 2 trial were to assess the safety and efficacy of Tolenix ™ in reducing the frequency of micturition (urination) and incontinence episodes per day, as compared to both placebo control and active control Detrol ® (tolterodine). In addition, common side effects of muscarinic antagonist therapies, such as dry mouth, were carefully assessed in the 138 patients enrolled in the trial. This international Phase 2 clinical trial was conducted in South Korea, Australia, and New Zealand.
Patients receiving Tolenix ™ (2mg tolterodine plus 9mg pilocarpine, administered BID) experienced statistically significant improvements in their OAB and UUI symptoms over placebo, with a reduction in daily micturitions of 0.88 (p<0.0001) and a reduction in daily incontinence episodes of 0.47 (p<0.0001). This efficacy was similar in magnitude to the maximum dose of active control Detrol ® (2mg tolterodine, administered BID).
Phase 1-Merck Serono, a division of Merck in Darmstadt, Germany, today announced aPhase 1- Merck Serono’s investigational drug sprifermin (recombinant human FGF-18) in osteoarthritis (OA) of the knee
recombinant human FGF-18
Darmstadt, Germany, March 18, 2013 –
Merck Serono, a division of Merck in Darmstadt, Germany, today announced a strategic alliance with Nordic Bioscience Clinical Development A/S on Merck Serono’s investigational drug sprifermin (recombinant human FGF-18) in osteoarthritis (OA) of the knee. This agreement underscores Merck Serono’s commitment to osteoarthritis research and development.
Under the terms of the agreement, Nordic Bioscience will provide clinical development services to Merck Serono on a shared-risk basis in exchange for a payment structure that includes service fees and potential milestone and royalty payments on the program. Merck Serono retains full responsibility for the development and commercialization of the investigational drug. Financial terms of the collaboration were not disclosed. The alliance will draw on the joint expertise and resources of Merck Serono and Nordic Bioscience to conduct a multi-national Phase IIb trial (the FORWARD study) to further evaluate sprifermin for inhibition of the progression of structural damage, reduction of pain and improvement of physical function in patients with OA of the knee. The FORWARD study is expected to begin enrollment in the second half of 2013.
The FDA has opened the inside track to Novartis’ experimental lung cancer drug, LDK378, which gained “Breakthrough Therapy” designation
The FDA has opened the inside track to Novartis’ experimental lung cancer drug, which gained “Breakthrough Therapy” designation that speeds the development and review schedules for new treatments. The Swiss drug giant plans to file for approval the drug, now in mid-stage clinical trials, in early 2014. Since clinical development began in 2011, the program has advanced with lightning speed compared with those that take 10 years or so to trial before submitted for approval.
While there are no guarantees of an FDA approval for Novartis’ compound, code-named LDK378, the “breakthrough” tag provides an early nod to the potential of the candidate to improve treatment for patients with metastatic non-small cell lung cancer with anaplastic lymphoma kinase (ALK) mutations.
The “breakthrough” designation is also important because Novartis’ compound and others with the coveted status have a shot to be approved by the FDA without completing all three phases of clinical trials typically required before an approval decision.
Novartis’ LDK378 joined the “breakthrough” club after showing an 80% response rate in patients studied in Phase I trial of 88 subjects with advanced cases of ALK-positive NSCLC. The company has already begun a pair of Phase II studies of the compound for patients with the same kind of ALK-positive cancers, which account for about 3% to 8% of cases of NSCLC. And plans call for kicking off Phase III development of the new drug later this year.
“LDK378 is a strong example of our research approach, which focuses on identifying the underlying cause of disease pathways,” said Alessandro Riva, Novartis’ global head of oncology development, in a statement. “This Breakthrough Therapy designation will allow us to collaborate more closely with the FDA and potentially to expedite the availability of an important new treatment option for patients with ALK+ NSCLC.”
Promising clips-Ferulic Acid: a Natural Antioxidant Against Oxidative Stress Induced by Oligomeric A-beta on Sea Urchin Embryo.
Source
Istituto di Biomedicina ed Immunologia Molecolare (IBIM)-CNR, via Ugo La Malfa 153, 90146, Palermo, Italy.
Abstract
Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder, characterized by loss of memory and impairment of multiple cognitive functions. Amyloid beta peptide (Aβ) is the main component of amyloid plaques observed in the brain of individuals affected by AD. Oxidative stress and mitochondrial dysfunction, induced by Aβ, are among the earliest events in AD, triggering neuronal degeneration and cell death. Use of natural molecules with antioxidant properties could be a suitable strategy for inhibiting the cell death cascade. Here, by employing the sea urchin Paracentrotus lividus as a model system, and Aβ oligomers, we tested the effectiveness of ferulic acid (FA), a natural antioxidant, as a putative AD neuroprotective compound. By microscopic inspection we observed that FA is able to reverse morphological defects induced by Aβ oligomers in P. lividus embryos. In addition, FA is able to neutralize reactive oxygen species (ROS), recover mitochondrial membrane potential, and block apoptotic pathways. Moreover, this model system has allowed us to obtain information about down- or up-regulation of some key molecules-Foxo3a, ERK, and p53-involved in the antioxidant mechanism
Ferulic acid is a hydroxycinnamic acid, a type of organic compound. It is an abundant phenolic phytochemical found in plant cell wall components such as arabinoxylans as covalent side chains. It is related to trans-cinnamic acid. As a component of lignin, ferulic acid is a precursor in the manufacture of other aromatic compounds. The etymology is from the genus Ferula, referring to the giant fennel (Ferula communis).
Nippon and Teva receive approval for biosimilar G-CSF (fligrastim) in Japan
As with the original drug, acts on neutrophil precursor cells, to promote the proliferation, differentiation and its biosimilar filgrastim of (recombinant) promotes the release of neutrophils from the bone marrow, enhances its function. In the field of cancer treatment, it is used for chemotherapy-induced neutropenia mainly cancer.
Filgrastim is a granulocyte colony-stimulating factor (G-CSF) analog used to stimulate the proliferation and differentiation of granulocytes.[1] It is produced by recombinant DNA technology. The gene for human granulocyte colony-stimulating factor is inserted into the genetic material of Escherichia coli. The G-CSF then produced by E. coli is different from G-CSF naturally made in humans.
It is marketed by Amgen under the brand name Neupogen, in India it is also marketed by Abbott Healthcare under the brand name Imumax, Dr. Reddy’s Laboratories under the brand name Grafeel, In Pakistan CCL Pharmaceuticals (Pvt) Ltd under the brand name Grastin, Zenotech Laboratories Limited under the brand name Nugraf, Raichem lifesciences under the brand name Shilgrast, Intas Biopharmaceuticals under the brand name Neukine, Emcure biopharmaceuticals under the brand name Emgrast, Reliance Life Sciences under the brand name Religrast and Sandoz under the name Zarzio.
Apricus Biosciences is currently developing and testing a product (under the brand name Nupen) which can deliver filgrastim through the skin to improve post-chemotherapy recovery of neutrophil counts.
ThromboGenics NV, European Commission has approved JETREA® (ocriplasmin) in the European Union
Leuven, March 15, 2013
ThromboGenics NV an integrated biopharmaceutical company focused on developing and commercializing innovative ophthalmic medicines, today announces that the European Commission has approved JETREA® (ocriplasmin) in the European Union. JETREA® is approved for the treatment of vitreomacular traction (VMT), including when associated with macular hole of diameter less than or equal to 400 microns. The EU approval triggers a €45 million milestone payment to ThromboGenics from its partner Alcon. The first sale of JETREA® in the EU by Alcon will trigger a further €45 million milestone payment to ThromboGenics.
Alcon, a division of Novartis, acquired the rights to commercialize JETREA® outside the United States in March 2012. ThromboGenics retains the right to commercialize the drug in the US. ThromboGenics launched JETREA® in the US in mid-January 2013 where it is approved for the treatment of patients with symptomatic vitreomacular adhesion (VMA).
Ocriplasmin (trade name Jetrea) is a recombinant protease with activity against fibronectin and laminin, components of the vitreoretinal interface. It is used for treatment of symptomatic vitreomacular adhesion, for which it received FDA approval on 17 October 2012. It works by dissolving the proteins that link the vitreous to the macula, resulting in posterior detachment of the vitreous from the retina.[1]
Intravenous formulation of Melphalan, which is in a Phase III trial for use as a conditioning treatment prior to autologous stem cell transplant for patients with multiple myeloma
Mephalan
15 march 2013
Spectrum Pharmaceuticals has licensed an investigational multiple myeloma drug from Ligand Pharmaceuticals in a deal that could be worth over $50 million.
The treatment in question is an intravenous formulation of melphalan, which is in a Phase III trial for use as a conditioning treatment prior to autologous stem cell transplant for patients with multiple myeloma. Spectrum is assuming the responsibility for the trial and hopes to file Captisol-enabled melphalan in the first half of 2014.
The Captisol technology used to reformulate melphalan allows for longer administration durations and slower infusion rates. It has been used with six US Food and Frug Administration-approved products, including Onyx Pharmaceuticals’ multiple myeloma drug Kyprolis (carfilzomib )and Pfizer’s antifungal Vfend (voriconazole).
Melphalan hydrochloride (trade name Alkeran) is a chemotherapy drug belonging to the class of nitrogen mustard alkylating agents.
An alkylating agent adds an alkyl group (CnH2n+1) to DNA. It attaches the alkyl group to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring.
Otherwise known as L-Phenylalanine Mustard, or L-PAM, melphalan is a phenylalanine derivative of mechlorethamine.
Uses
It is used to treat multiple myeloma[1] and ovarian cancer, and occasionally malignant melanoma.
The agent was first investigated as a possible drug for use in melanoma. It was not found to be effective, but has been found to be effective in the treatment of myeloma.
Oral or intravenous; dosing varies by purpose and route of administration as well as patient weight.
Melphalan Prescribing Information: Alkeran[2]
Melphalan Patient Information: MedlinePlus[3]
Melphalan Material Safety Data Sheet (MSDS): Sequoia Research Products[4]
- Facon T, Mary JY, Hulin C, et al. (October 2007). “Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial”. Lancet 370 (9594): 1209–18. doi:10.1016/S0140-6736(07)61537-2. PMID 17920916.
- celgene.com
- nlm.nih.gov
- seqchem.com
New Drug Approvals 