CGP3466B compound may effectively treat depression

We know that, Omigapil (TCH346 or CGP3466) is a drug that was developed by Novartis and tested in clinical trials for its ability to help treat Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). The development for PD and ALS have been terminated due to lack of benefit, but Santhera Pharmaceuticals bought the compound for development for the treatment of congenital muscular dystrophy (CMD). Omigapil was first synthesized at Ciba-Geigy, Basel, Switzerland. Santhera Pharmaceuticals has since taken over production of omigapil and preclinical trials for CMD. In May 2008, omigapil was granted orphan designation to commence clinical trials for. Pharmacokinetic trials are scheduled to commence enrollment in the second half of 2012 to determine the appropriate pharmacokinetic profile of the drug for children with laminin-α2-deficient congenital muscular dystrophy (MDC1A) and collagen VI related myopathy. Santhera Pharmaceuticals will use the phase 1 clinical trial to determine if the drug is safe and acts with the same pharmacokinetic profile in children as it does in adults. The impending clinical trial will take place in the United States at the National Institute of Neurological Disorders and Stroke/National Institute of Health(NNDCS/NINDS) (Bethesda, Maryland) and in the United Kingdom at Great Ormond Street Hospital (UCL

The compound CGP3466B, already proven nontoxic for people, may effectively and rapidly treat depression, according to results of a study in mice. The Johns Hopkins Medicine neuroscientists who conducted the research say that the compound -- previously shown to block cocaine craving in the brains of rodents -- delivers antidepressant effects to mice within hours instead of weeks or months, like currently available antidepressants. The results of the study will be summarized Jan. 12 online in the journal Molecular Psychiatry.

"One of the promising things about CGP3466B is that it targets a new network of proteins," says Solomon Snyder, M.D., professor of neuroscience at the Johns Hopkins University School of Medicine. "That means it may work in patients who are unresponsive to other types of drugs and it lays the foundation for the development of a new class of fast-acting antidepressants that target the same network."

The team's discovery came out of investigations into the workings of a different drug, ketamine, long used primarily at high doses to induce anesthesia during surgery but known, at lower doses, to be a fast-acting antidepressant. Unfortunately, Snyder says, ketamine is addictive and can produce schizophrenialike symptoms, making it unsuitable for prolonged use, but his team hoped it could shed light on how to make a better fast-acting antidepressant.

CGP3466B compound may effectively treat depression: 

Mylan announces launch of Linezolid Tablets, 600 mg in U.S.

In continuation of my update on Linezolid

Mylan N.V.  announced the U.S. launch of Linezolid Tablets, 600 mg, which is the generic version of Pfizer's Zyvox® Tablets. Mylan received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product, which is indicated in adults and children for the treatment of certain infections caused by susceptible Gram-positive bacteria.

Linezolid Tablets, 600 mg, had U.S. sales of approximately $457.8 million for the 12 months ending Sept. 30, 2015, according to IMS Health.

Currently, Mylan has 269 ANDAs pending FDA approval representing $100.8 billion in annual brand sales, according to IMS Health. Fifty of these pending ANDAs are potential first-to-file opportunities, representing $35.6 billion in annual brand sales, for the 12 months ending June 30, 2015, according to IMS Health.

Mylan announces launch of Linezolid Tablets, 600 mg in U.S.

UTA chemists design efficient water-based system for synthesis of organic compounds

Chemists at The University of Texas at Arlington have devised a safer, more environmentally friendly, less expensive and more efficient water-based system for the synthesis of organic compounds typically used in pharmaceuticals, agrochemicals, cosmetics, plastics, textiles and household chemicals.

Most organic synthesis depends heavily on volatile organic solvents, which typically pose significant environmental and health hazards and also are costly.

"Our new system could facilitate cheaper, safer and more efficient industrial reactions across a variety of sectors dependent on synthesis of organic compounds," said Morteza Khaledi, dean of UTA's College of Science and co-investigator of the project. "Using water as a solvent is ideal as it is benign, plentiful, cheap and not harmful to the environment."

The new medium, 80-90 percent water with fluoroalcohol, supports the synthetic reaction of organic compounds and even produces considerably higher yields of product than pure organic solvents.

The system also demonstrates the additional advantage that the mixture forms two separate phases during the reaction, which means that the resulting products can be easily separated and centrifuged out of the mixture. Typically, additional organic solvents are used to facilitate the separation and extraction of product.

"This is a clear step forward towards a "green" organic synthesis process and fits into UTA's strategic focus on Global Environmental Impact within the Strategic Plan 2020," Dean Khaledi said. "The organic solvent can even be recycled after the reaction, which is an additional bonus for the environment. "

UTA chemists design efficient water-based system for synthesis of organic compounds: Chemists at The University of Texas at Arlington have devised a safer, more environmentally friendly, less expensive and more efficient water-based system for the synthesis of organic compounds typically used in pharmaceuticals, agrochemicals, cosmetics, plastics, textiles and household chemicals.

New oral breast cancer drug has potential to combat other types of cancer

In continuation of my update on Palbociclib

Palbociclib, a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has potential to combat other types of cancer, according to a literature review and additional original research conducted by experts at the Abramson Cancer Center (ACC) in the University of Pennsylvania published this month in JAMA Oncology.

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division and increase in number in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer.

"All living cells undergo cell division and palbociclib's unique capacity to halt the cell division process (also known as the 'cell cycle') therefore has potentially broad applicability," said the study's lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at Penn's Perelman School of Medicine and ACC. "Pairing palbociclib with other anti-cancer therapies such as endocrine therapy, chemotherapy, and targeted therapy can create a powerful combinatorial effect with real promise for addressing a variety of cancers." For example, amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.

Targeted therapy uses medication and other interventions to more accurately identify and attack cancer cells, usually while doing no or little damage to normal cells.

"This drug has minor effects on normal cells other than neutrophils (white blood cells)," said the study's senior author, Peter J. O'Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC. "In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anti-cancer agents work better."

New oral breast cancer drug has potential to combat other types of cancer

Potent parasite-killing mechanism of anti-malarial drug uncovered: New understanding of how artemisinin works could facilitate development of new drugs and therapeutic strategies against malaria -- ScienceDaily

In continuation of my update on artemisinin

A team of researchers has uncovered the mystery behind the potent parasite-killing effect of artemisinin, a drug that is considered to be the last line of defense against malaria. Given the emergence of artemisinin resistance, these findings could potentially lead to the design of new treatments against drug-resistant parasites.

Assistant Professor Lin Qingsong, who is from the Department of Biological Sciences under the NUS Faculty of Science and is one of the scientists who led the study, explained, "Many people may not realise that more human lives are lost to the tiny mosquito, more specifically malaria parasites, each year as compared to ferocious animals such as lions and sharks. After infection, malaria parasites, known for their blood-eating nature, can propagate inside the human body rapidly and consume up to 80 per cent of red blood cells in a short period of time, leading to a series of deadly symptoms."

About 3.2 billion people -- almost half of the world's population -- are considered to be at risk of malaria by the World Health Organization. As of September 2015, there were an estimated 214 million cases of malaria and 438,000 malaria-linked deaths this year alone.

Artemisinin and its derivatives are currently the most potent class of anti-malarial drugs. In recognition of its importance against malaria, the discovery of artemisinin won Chinese scientist Ms Tu Youyou the 2015 Nobel Prize in Physiology or Medicine earlier in October this year. While there have been extensive studies on artemisinin, the mechanism of the drug is not well understood.

Asst Prof Lin, together with Dr Wang Jigang, who was formerly with the NUS Department of Biological Sciences and now with the Singapore-MIT Alliance for Research & Technology, Associate Professor Kevin Tan from the Department of Microbiology and Immunology at the NUS Yong Loo Lin School of Medicine and their research team, discovered over 120 protein targets of artemisinin, and the mechanism that activates its deadly killing effect. The findings of the study are published in the journal Nature Communications on 23 December 2015.

Potent parasite-killing mechanism of anti-malarial drug uncovered: New understanding of how artemisinin works could facilitate development of new drugs and therapeutic strategies against malaria

New Breast Cancer Drug May Be Effective Against Other Types of Cancer, Abramson Cancer Center Experts Find

In continuation of my update on Palbociclib,

Palbociclib, a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has potential to combat other types of cancer, according to a literature review and additional original research conducted by experts at the Abramson Cancer Center (ACC) in the University of Pennsylvania published this month in JAMA Oncology.

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division and increase in number in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer.

“All living cells undergo cell division and palbociclib’s unique capacity to halt the cell division process (also known as the ‘cell cycle’) therefore has potentially broad applicability,” said the study’s lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at Penn’s Perelman School of Medicine and ACC. “Pairing palbociclib with other anti-cancer therapies such as endocrine therapy, chemotherapy, and targeted therapy can create a powerful combinatorial effect with real promise for addressing a variety of cancers.” For example, amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.

Targeted therapy uses medication and other interventions to more accurately identify and attack cancer cells, usually while doing no or little damage to normal cells. 

“This drug has minor effects on normal cells other than neutrophils (white blood cells),” said the study’s senior author, Peter J. O’Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC. “In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anti-cancer agents work better.”

In addition to inhibiting the cell cycle, palbociclib has been shown, for example, to alter several recently described non–cell cycle functions of CDK4/6, a finding expected to expand its therapeutic role, O’Dwyer added.

Assessing 130 relevant publications in the literature, as well as interpreting their own continuing studies, the all-Penn team found that in addition to its safety and effectiveness in fighting certain types of breast cancer, early trials of palbociclib have shown promise of effectiveness in cases of lymphoma, sarcoma, and teratoma, tumors that while rare, often afflict younger patients.

A phase 2 trial showed that, among 17 patients with previously treated mantle-cell lymphoma, palbociclib resulted in one complete response and two partial responses. Although, median progression-free survival was four months, five patients had progression-free survival greater than one year. Another phase 2 trial with 29 sarcoma patients treated with palbociclib showed a progression-free survival of 66 percent at 12 weeks.

Also, combining palbociclib with other anti-cancer agents is feasible, and early results in myeloma and some solid tumors have led to more definitive studies.

New Breast Cancer Drug May Be Effective Against Other Types of Cancer, Abramson Cancer Center Experts Find

Afatinib a better choice for EGFR-mutated lung cancer in first-line treatment

In continuation of my update on Afatinib

Patients with EGFR-activating mutations in advanced lung cancer seem to benefit more from afatinib than gefitinib as first-line treatment, researchers report at the first ESMO Asia 2015 Congress in Singapore.

In the global, randomised, open-label Phase IIb LUX-Lung 7 (LL7) trial1, the irreversible ErbB family blocker afatinib significantly improved efficacy versus gefitinib across a range of clinically relevant endpoints, such as progression-free survival, time-to-treatment failure and objective response rate. "Based on these results I would consider afatinib as the EGFR tyrosine kinase inhibitor (TKI) of choice for the first-line treatment for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC)," lead author, Professor Keunchil Park, head of the Division of Hematology/Oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, said.

NSCLC is the most common type of lung cancer: activating epidermal growth factor receptor (EGFR) gene mutations are more frequently observed in non-smokers and women, and occur in 50% of Asians and only 10% of non-Asians. The targeted agents afatinib and gefitinib block key pathways involved in tumour growth and spread. They have both been approved for the treatment of naive patients, based on the results of Phase III trials, confirming their superiority compared to chemotherapy. Unlike the first-generation EGFR inhibitor gefitinib, the irreversible ErbB family blocker afatinib is suggested to be active in prolonging tumour response and delaying disease progression.

Afatinib a better choice for EGFR-mutated lung cancer in first-line treatment - Medical News Today

Osteoarthritis: pivotal Phase III trial successfully meets primary efficacy endpoint - Medical News Today

Celecoxib/amlodipine besylate (KIT-302)

  

itov Pharmaceuticals, an innovative biopharmaceutical company focused on late-stage drug development, announced today that the Phase III, double-blind, placebo-controlled clinical trial for its leading drug candidate, KIT-302, successfully met the primary efficacy endpoint of the trial protocol as approved by the U.S. Food & Drug Administration (FDA). Data from the trial further revealed that KIT-302 was more efficacious at reducing hypertension than the widely used hypertension drug amlodipine besylate. Kitov plans to file its New Drug Application (NDA) for marketing approval of KIT-302 with the FDA in the second half of 2016.

A combination drug, KIT-302, simultaneously treats pain caused by osteoarthritis and treats hypertension, which is a common side effect of stand-alone drugs that treat osteoarthritis pain. KIT-302 is comprised of two FDA approved drugs, celecoxib (Celebrex®) for the treatment of pain caused by osteoarthritis and amlodipine besylate, a drug designed to treat hypertension.

The trial protocol, approved by the FDA through the Special Protocol Assessment process, was designed to quantify the decrease of hypertension in patients receiving KIT-302. The trial was performed in the U.K. in four groups of twenty-six (26) to forty-nine (49) patients, with a total of 152 patients. Each patient was treated over a total period of two weeks. Group One was treated with KIT-302, comprised of celecoxib and amlodipine besylate. Group Two was treated with amlodipine besylate only, one of the components of KIT-302. Group Three was treated with celecoxib only, the other component of KIT-302. Group Four was treated with a double placebo. The trial began in June 2014 and was completed in November 2015.

Osteoarthritis: pivotal Phase III trial successfully meets primary efficacy endpoint - Medical News Today

FDA approves non-alcoholic Docetaxel Injection

In continuation of my update on Docetaxel

Teikoku Pharma USA, Inc. ("Teikoku" or "the Company") announced today that the U.S. Food and Drug Administration ("FDA") has approved Docetaxel Injection, Non-Alcohol Formula ("Docetaxel Injection") for the treatment of breast cancer, non-small cell lung cancer, prostate cancer, gastric adenocarcinoma, and head and neck cancer. Teikoku entered into an exclusive licensing agreement with Eagle Pharmaceuticals Inc. ("Eagle Pharmaceuticals") in October 2015 to market, sell and distribute Docetaxel Injection in the U.S.

The main difference, compared to other docetaxel formulations, is that Docetaxel Injection is the first non-alcohol formulation approved in the U.S. Further differentiating it from some of the currently marketed docetaxel formulations is that Teikoku's Docetaxel Injection:

• Requires no prior dilution with a diluent and is ready to add to the infusion solution; and
• Is available in three presentations: 20mg/ml in single-dose vials, and 80 mg/4 mL or 160 mg/8 mL in multiple-dose vials.............

FDA approves non-alcoholic Docetaxel Injection

Teva Pharmaceuticals and Eagle Pharmaceuticals Announce FDA Approval of Bendeka (bendamustine hydrochloride) Injection

Teva Pharmaceutical Industries Ltd. (NYSE:TEVA) and Eagle Pharmaceuticals, Inc. (Nasdaq:EGRX) today announce that the U.S. Food and Drug Administration (FDA) has approved Bendeka, (bendamustine hydrochloride) injection, a liquid, low-volume (50 mL) and short-time 10-minute infusion formulation of bendamustine. Bendeka is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) and for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Efficacy in CLL relative to first-line therapies other than chlorambucil has not been established. “We are thrilled that the FDA has approved Bendeka and are excited for what we believe will be a promising launch with Teva. Importantly, we believe that patients with CLL or indolent B-cell NHL that has progressed will benefit from the multiple administration options this product offers,” said Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals.

“Teva looks forward to commercializing this new bendamustine product, which we believe represents an important benefit to both patients and healthcare providers,” said Paul Rittman, Senior Vice President and General Manager, Teva Oncology. “We are pleased to add Bendeka to Teva’s Oncology portfolio, and bendamustine franchise, furthering our commitment to enhancing treatment options for patients affected by cancer.”

Bendeka was granted Orphan Drug Designations for both CLL and indolent B-cell NHL.

Under the February 2015 exclusive license agreement for Bendeka, Teva is responsible for all U.S. commercial activities for the product including promotion and distribution. Teva expects to make Bendeka commercially available to prescribers during the first quarter of 2016.

Teva Pharmaceuticals and Eagle Pharmaceuticals Announce FDA Approval of Bendeka (bendamustine hydrochloride) Injection

FDA Approves Bridion (sugammadex) to Reverse Effects of Neuromuscular Blocking Drugs

"Bridion provides a new treatment option that may help patients recover sooner from medications used for intubation or ventilation during surgery,” said Sharon Hertz, The U.S. Food and Drug Administration today approved Bridion (sugammadex) injection to reverse the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide, which are used during certain types of surgery in adults.

Rocuronium bromide and vecuronium bromide are neuromuscular blocking drugs that cause temporary paralysis by interfering with the transmission of nerve impulses to the muscle and are used to paralyze the vocal cords when patients require an artificial airway or breathing tube for surgery, a process called tracheal intubation. They can also be used to prevent patients from moving during surgery while they are receiving general anesthesia. Neuromuscular blocking drugs are also sometimes used to prevent the body from breathing automatically when a patient has to be placed on a ventilator.

M.D., director of the Division of Anesthesia, Analgesia and Addiction Products in the FDA’s Center for Drug Evaluation and Research. “This drug enables medical personnel to reverse the effects of neuromuscular blocking drugs and restore spontaneous breathing after surgery.

FDA Approves Bridion (sugammadex) to Reverse Effects of Neuromuscular Blocking Drugs

FDA Approves Uptravi (selexipag) for Pulmonary Arterial Hypertension

On December 21, the U.S. Food and Drug Administration approved Uptravi (selexipag) tablets to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive, and debilitating rare lung disease that can lead to death or the need for transplantation. “Uptravi offers an additional treatment option for patients with pulmonary arterial hypertension,” said Ellis Unger, M.D., director of the Office of Drug Evaluation I in the FDA’s Center for Drug Evaluation and Research. “The FDA supports continued efforts to provide new treatment options for rare diseases.”

PAH is high blood pressure that occurs in the arteries that connect the heart to the lungs. It causes the right side of the heart to work harder than normal, which can lead to limitations on exercise ability and shortness of breath, among other more serious complications.

Uptravi belongs to a class of drugs called oral IP prostacyclin receptor agonists. The drug acts by relaxing muscles in the walls of blood vessels to dilate (open) blood vessels and decrease the elevated pressure in the vessels supplying blood to the lungs.

Uptravi’s safety and efficacy were established in a long-term clinical trial of 1,156 participants with PAH. Uptravi was shown to be effective in reducing hospitalization for PAH and reducing the risks of disease progression compared to placebo. Participants were exposed to Uptravi in this trial for a median duration of 1.4 years.

FDA Approves Uptravi (selexipag) for Pulmonary Arterial Hypertension

FDA Approves Alecensa (alectinib) for ALK-Positive Non-Small Cell Lung Cancer

The U.S. Food and Drug Administration today approved Alecensa (alectinib) to treat people with advanced (metastatic) ALK-positive non-small cell lung cancer (NSCLC) whose disease has worsened after, or who could not tolerate treatment with, another therapy called Xalkori (crizotinib).

Lung cancer is the leading cause of cancer death in the United States, with an estimated 221,200 new diagnoses and 158,040 deaths in 2015, according to the National Cancer Institute. An ALK (anaplastic lymphoma kinase) gene mutation can occur in several different types of cancer cells, including lung cancer cells. ALK gene mutations are present in about 5 percent of patients with NSCLC. In metastatic cancer, the disease spreads to new parts of the body. In ALK-positive NSCLC metastatic patients, the brain is a common place for the disease to spread.

“Today’s approval provides a new therapy for a group of patients who would have few treatment options once their disease no longer responds to treatment with Xalkori,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “In addition to the primary effect on tumors in the lung, Alecensa clinical trials provide evidence of an effect on tumors that had spread to the brain, which is an important effect for clinicians to understand.”

Alecensa is an oral medication that blocks the activity of the ALK protein, which may prevent NSCLC cells from growing and spreading.

The safety and efficacy of Alecensa were studied in two single-arm clinical trials of patients with metastatic ALK-positive

FDA Approves Alecensa (alectinib) for ALK-Positive Non-Small Cell Lung Cancer

FDA Approves Zurampic (lesinurad) to Treat High Blood Uric Acid Levels Associated with Gout

The U.S. Food and Drug Administration today approved Zurampic (lesinurad) to treat high levels of uric acid in the blood (hyperuricemia) associated with gout, when used in combination with a xanthine oxidase inhibitor (XOI), a type of drug approved to reduce the production of uric acid in the body. Gout is a painful form of arthritis caused by the buildup of too much uric acid in the body, and usually appears first as redness, soreness, and swelling in the big toe. Uric acid in the blood is produced by the breakdown of substances called purines, which are found in all the body’s tissues. Uric acid usually dissolves in the blood then passes through the kidneys and out of the body in urine. Uric acid can build up in the blood, a condition called hyperuricemia. This occurs when the body increases the amount of uric acid it makes, the kidneys do not get rid of enough uric acid, or a person eats too many foods high in purines. Most people with hyperuricemia do not develop gout, but if uric acid forms crystals in the body, gout can develop.

"Controlling hyperuricemia is critical to the long-term treatment of gout," said Badrul Chowdhury, M.D., director of the Division of Pulmonary, Allergy and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research. "Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes."

Zurampic works by helping the kidney excrete uric acid. It does this by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.

The safety and efficacy for Zurampic were evaluated in three randomized, placebo-controlled studies in combination with a XOI involving 1,537 participants for up to 12 months. Participants treated with Zurampic in combination with a XOI experienced reduced serum uric acid levels compared to placebo.

FDA Approves Zurampic (lesinurad) to Treat High Blood Uric Acid Levels Associated with Gout

New type of hydrogen bond discovered

An entirely new class of hydrogen bond that forms between a boron–hydrogen group and the aromatic, π-electron system of a benzene ring has been discovered. The non-classical B–H…π bond can be seen in the gas phase locking together diborane and benzene with a strength comparable to the hydrogen bonds that hold water dimers together

New type of hydrogen bond discovered 

EMA CHMP considers AcelRx's ARX-04 for acute pain treatment for centralized review

AcelRx Pharmaceuticals, Inc. (Nasdaq: ACRX), a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for the intended treatment of acute pain, reported that the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA) has confirmed that a Marketing Authorization Application (MAA) for ARX-04 may be submitted in the European Union (EU) under the Agency's centralized procedure. ARX-04 (sufentanil sublingual tablet, 30 mcg) is being developed for the treatment of moderate-to-severe acute pain in adult patients administered by a healthcare professional in a medically supervised setting.

ARX-04 is a non-invasive, fast-onset sufentanil product candidate under investigation.

"We appreciate the CHMP's consideration of ARX-04 for regulatory review under the centralized process, which we expect will make our planned MAA filing with the EMA much more efficient," commented Dr. Pamela Palmer, co-founder and chief medical officer of AcelRx. "The EMA's centralized procedure is typically limited to products the EMA believes constitute significant therapeutic, scientific or technical innovations, characteristics we believe ARX-04 possesses."

For eligible drugs, the centralized procedure permits the submission of a single marketing application to the EMA that, if approved, allows the drug to be marketed in all 27 EU member states, as well as in the three European Economic Area (EEA) countries: Iceland, Liechtenstein and Norway.

ARX-04 is currently being studied in an open-label Phase 3 study (SAP302) in adult patients who present in the emergency room with acute moderate-to-severe pain associated with trauma or injury, and an additional Phase 3 study (SAP303) is planned in postoperative patients with acute moderate-to-severe pain. An earlier Phase 3 trial (SAP301) in patients with acute moderate-to-severe pain following ambulatory abdominal surgery demonstrated that patients administered ARX-04 experienced significantly greater pain relief compared to those receiving placebo, as measured by the time-weighted summed pain intensity difference over the first 12 hours of treatment (SPID12) (p<0.001). AcelRx expects to file marketing applications to both the EMA and the U.S. Food and Drug Administration (FDA) for ARX-04.

EMA CHMP considers AcelRx's ARX-04 for acute pain treatment for centralized review

Opicapone simplifies levodopa-related motor fluctuation treatment

Once-daily opicapone is effective for the treatment of end-of-dose motor fluctuations in patients receiving levodopa for Parkinson’s disease, phase III study findings show.

The results indicate that at a dose of 50 mg/day the drug, a potent third-generation catechol-O-methyltransferase (COMT) inhibitor, was superior to placebo and non-inferior to entacapone (200 mg with each levodopa dose) in reducing the absolute time patients spent in the off state.

The magnitude of effect with opicapone was greater that than of entacapone, with a 26.2 minute greater reduction in the time spent in the off state after 14–15 weeks of treatment and a 60.8 minute greater reduction compared with placebo.

Opicapone 50 mg “is, therefore, the only once-daily COMT inhibitor to provide a mean reduction in time in the off state that is clinically relevant,” say Patrício Soares-da-Silva (BIAL, Coronado, Portugal) and team.

The average changes from baseline in time spent in the off state over a 24-hour period were 116.8 minutes in 115 patients taking opicapone 50 mg/day, 96.3 minutes in 120 patients taking entacapone and 56.0 minutes in the placebo group.

Opicapone 25 mg and 5 mg were also tested in 116 and 119 patients, respectively, but the effects of these doses on the time patients spent in the off state did not differ significantly from that of placebo.

The researchers note in The Lancet Neurology that, in addition to greater reductions in the time patients spent in the off state, opicapone 50 mg was associated with greater increases in the percentage of time patients spent in the on state without troublesome dyskinesia, with a 5.4% difference compared with placebo and a 1.2% difference compared with entacapone.

Improvements in global symptoms were seen in significantly more patients taking opicapone 50 mg than in those taking entacapone, and while numerical improvements in motor symptom scores were seen in all groups, differences between active treatment and placebo groups were not significant.

Opicapone simplifies levodopa-related motor fluctuation treatment

Selexipag holds promise for treatment of pulmonary hypertension

Living with pulmonary arterial hypertension is challenging, but the chore of treating the rare heart disease may change following promising clinical trial data to be published in the Dec. 24 issue of the New England Journal of Medicine.

Data from the largest study ever of pulmonary hypertension shows the oral medication Selexipag led to a 40 percent reduction in hospitalizations and worsening symptoms among patients with pulmonary hypertension.

Selexipag targets a well-known disease pathway that opens blood vessels to the lungs and improves heart function and is easier to use than PH treatments delivered with infusions or injections.

"For more than two decades we've targeted the prostacyclin pathway to induce vasodilation in these blood vessels in the lung," says senior study author Vallerie McLaughlin, M.D., director of the University of Michigan Pulmonary Hypertension Program.

"But because of the cumbersome nature of treatment, patients would often wait until late stages to begin therapy. Having an oral medication to attack the disease pathway will be a major advancement because less ill patients will be willing to begin this therapy," McLaughlin says.

Selexipag demonstrated effectiveness while its most frequent adverse events were headache, diarrhea, nausea, muscle pain and joint pain. The side effects were considered consistent with prostacyclin therapy.

The medication is not commercially available. Following the phase 3 clinical trial, the U.S. Food and Drug Administration is evaluating the drug.

Pulmonary hypertension, which is high blood pressure in the loop of blood vessels connecting the heart and lungs, can make everyday activities exhausting. It often leads to life-threatening heart failure as the heart works harder to pump blood to the lungs.

The greatest number of cases is reported in women between ages 21 and 40 who most often experience fatigue and shortness of breath.

While a rare disease, research of causes and treatment of pulmonary hypertension is growing. The GRIPHON study is a standout because of its size and scope, enrolling 1,156 patients with pulmonary hypertension from 181 centers from 39 countries in North and South America, Europe, Asia-Pacific and Africa.

Selexipag holds promise for treatment of pulmonary hypertension

Positive interim results from TWIB's AC-201 CR Phase 2 study for hyperuricemia and gout

TWi Biotechnology Inc. today announced interim results from the ongoing Phase 2 proof of concept clinical study evaluating AC-201 CR as an oral uricosuric and anti-inflammatory agent for the treatment of hyperuricemia and prevention of gout flares combining with febuxostat, (see structure) a xanthine oxidase inhibitor.

The interim analysis is for the first enrollment cohort (18 per arm completing Week 8), if the number of subjects in the AC-201 CR arm achieving the clinical target of sUA <6.0 mg/dL at Week 8 is at least 2 greater than the number in the placebo arm, then the remaining subjects will be enrolled in the second cohort; if not, enrollment will be stopped. Based on the report, the responders in AC-201 CR arm is at least 2 greater than the number in the placebo arm. In addition to producing the efficacy of AC-201 CR in gout patients, there have been no serious adverse events reported to date and AC-201 CR was generally safe and well tolerated in the study patients. Therefore, TWIB is able to continue to enroll second cohort subjects and complete this clinical trial in the end of 2016.

"We are encouraged to see the potential efficacy of AC-201 CR in the Phase 2 proof-of-concept study results to date," said Dr. Calvin C. Chen, President and CEO of TWIB. "Current evidence of AC-201 CR efficacy and the preliminary results for tolerance support the potential of AC-201 CR as a dual uricosuric and anti-inflammatory agent for the treatment of hyperuricemia and the prevention of gout flares when combining with xanthine oxidase inhibitor. I am very pleased with the interim data as it indicates AC-201 CR may increase the successful rate of the treatment of gout without increase or even decrease the flare rate. The poor compliance of the urate lowering therapy due to frequent gout flares at the initiation and low treatment successful rate offered by existing therapies are the major unmet needs for the management of sUA and gout."

Positive interim results from TWIB's AC-201 CR Phase 2 study for hyperuricemia and gout

HBI-8000 granted orphan drug designation in Japan for treatment of peripheral T-cell lymphoma

HUYA Bioscience International (HUYA), Founder, CEO & Executive Chair, Dr. Mireille Gillings today announced that the Ministry of Health, Labour and Welfare (MHLW) granted HBI-8000 orphan drug designation in Japan for peripheral T-cell lymphoma (PTCL). HBI-8000 is a novel class I-selective oral histone deacetylase (HDAC) inhibitor with immunomodulatory effects regulating antitumor activity, as well as repression of genes associated with drug resistance. The product is currently completing a Phase 1 open-label, dose escalation trial in Japan to evaluate the safety and pharmacokinetics of HBI-8000 in Japanese patients with non‑Hodgkin's lymphoma (NHL). The orphan drug designation was based on the estimated size of the Japanese PTCL patient population, the non-clinical and clinical studies as well as the clinical development plan in Japan.

"The breadth of activity of HBI-8000 is now emerging strongly as more studies are conducted. The orphan drug designation for PTCL is an important demonstration of efficacy to combat a devastating unmet need," said Dr. Mireille Gillings, Founder, CEO & Executive Chair of HUYA. "With the orphan drug designation, HBI-8000 should benefit from a priority review for marketing authorization and a 10-year market exclusivity as well as financial incentives."

Under the Tripartite Cooperation Treaty between China, South Korea and Japan and given the recent approval of the drug for the treatment of PTCL in China, HUYA launched development of HBI-8000 in Japan for NHL. The Company plans to begin a Phase 2 registration trial in 2016 based on the Pharmaceutical and Medical Devices Agency's (PMDA) acceptance of HUYA's accelerated development strategy for Japan.

HBI-8000 granted orphan drug designation in Japan for treatment of peripheral T-cell lymphoma

Azithromycin remains effective in treatment of urogenital chlamydia, confirms UAB study

 

In continuation of my update on azithromycin...

In one of the most tightly controlled trials ever conducted of drugs used to treat sexually transmitted infections, researchers at the University of Alabama at Birmingham have confirmed that azithromycin remains effective in the treatment of urogenital chlamydia.

In a study published Dec. 24 in the New England Journal of Medicine, the research team compared two of the most commonly used medications for urogenital chlamydia — a single dose of azithromycin versus doxycycline given twice daily for seven days. Azithromycin had a cure rate of 97 percent, against a 100 percent cure rate for doxycycline.

"Recent studies have raised concerns over the efficacy of azithromycin, and there has not been a definitive, well-controlled randomized clinical trial of its effectiveness," said William M. Geisler, M.D., professor in the Division of Infectious Diseases in the UAB Department of Medicine and principal investigator of the study. "For physicians, knowing whether azithromycin is an effective treatment option is important because patient adherence to therapy with doxycycline can be an issue. Azithromycin requires only one dose, while doxycycline requires patients to take multiple pills over seven days.

Studies have shown that patients are much more likely to be adherent to therapy when taking a single dose compared to multiple doses over time. Failure to take all of a prescribed medicine can allow the condition being treated to persist.

Geisler's team partnered with researchers at the University of Southern California and the Los Angeles County Department of Health Services. They enrolled 567 male and female subjects ages 12-21 with chlamydia residing in long-term, gender-segregated youth correctional facilities in Los Angeles. Half were given azithromycin and half doxycycline.

Azithromycin remains effective in treatment of urogenital chlamydia, confirms UAB study

Zurampic (lesinurad) approved to treat high levels of hyperuricemia associated with gout

The U.S. Food and Drug Administration today approved Zurampic (lesinurad) to treat high levels of uric acid in the blood (hyperuricemia) associated with gout, when used in combination with a xanthine oxidase inhibitor (XOI), a type of drug approved to reduce the production of uric acid in the body.

Gout is a painful form of arthritis caused by the buildup of too much uric acid in the body, and usually appears first as redness, soreness, and swelling in the big toe. Uric acid in the blood is produced by the breakdown of substances called purines, which are found in all the body's tissues. Uric acid usually dissolves in the blood then passes through the kidneys and out of the body in urine. Uric acid can build up in the blood, a condition called hyperuricemia. This occurs when the body increases the amount of uric acid it makes, the kidneys do not get rid of enough uric acid, or a person eats too many foods high in purines. Most people with hyperuricemia do not develop gout, but if uric acid forms crystals in the body, gout can develop.

Controlling hyperuricemia is critical to the long-term treatment of gout," said Badrul Chowdhury, M.D., director of the Division of Pulmonary, Allergy and Rheumatology Products in the FDA's Center for Drug Evaluation and Research. "Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes."

Zurampic works by helping the kidney excrete uric acid. It does this by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.

The safety and efficacy for Zurampic were evaluated in three randomized, placebo-controlled studies in combination with a XOI involving 1,537 participants for up to 12 months. Participants treated with Zurampic in combination with a XOI experienced reduced serum uric acid levels compared to placebo.

The most common adverse reactions in clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease.

Zurampic has a boxed warning that provides important safety information for health care professionals, including the risk for acute kidney (renal) failure, which is more common when used without an XOI and with higher than approved doses of Zurampic.

The FDA is also requiring a postmarketing study to further evaluate the renal and cardiovascular safety of Zurampic.

Zurampic (lesinurad) approved to treat high levels of hyperuricemia associated with gout

Add-on lamotrigine enhances bipolar depression treatment

Combining lamotrigine with quetiapine improves the treatment of depressive symptoms in patients with bipolar disorder, with the benefits maintained for at least a year, show findings from the CEQUEL trial.

Scores on the Quick Inventory of Depressive Symptomatology–self report version 16 (QIDS-SR16) at 12 weeks were, on average, 1.73 points lower among 101 moderately depressed bipolar patients randomly assigned to receive lamotrigine (25 mg/day titrated to 200 mg/day) in addition to quetiapine, compared with 101 assigned to receive add-on placebo.

By 52 weeks, the difference was significant at an average of 2.69 points lower for those taking add-on lamotrigine, after taking into account age, bipolar disorder type and dose of quetiapine (< or ≥300 mg/day), the researchers led by John Geddes (University of Oxford, UK) report in The Lancet Psychiatry.

They also found that significantly more patients taking lamotrigine plus quetiapine were in remission at 12 weeks (31 vs 16%) and 52 weeks (36 vs 13%), with relative risks of 2.11 and 3.73, respectively.

Discussing the findings in a related comment, Gin Malhi (University of Sydney, New South Wales, Australia) says: “[T]he investigators skillfully take advantage of the synergy between quetiapine and lamotrigine that arises from their differing, but complementary, mechanisms of action and the separate timescales over which they exert their effects.”

He explains that quetiapine is often given in the short term to ameliorate acute symptoms, whereas lamotrigine is more effective over the longer term. The drug is therefore able to “achieve a therapeutic level and exert its actions under the initial cover of the antipsychotic, which can then be gradually tapered and withdrawn”, he writes.

Add-on lamotrigine enhances bipolar depression treatment

IASLC lauds FDA approval of alectinib for lung cancer treatment

The International Association for the Study of Lung Cancer (IASLC) is once again gratified to see the approval of a new second-generation lung cancer treatment that can help many patients in their battle against the disease. Lung cancer patients got another round of hope with the FDA's rapid progression of lung cancer drug approvals - this time for alectinib (Alecensa, Roche/Genenetech) for patients with advanced (metastatic) ALK-positive non-small cell lung cancer (NSCLC) if their disease deteriorated after treatment with another therapy called crizotinib (Xalkori, Pfizer). Patients who could not tolerate treatment with crizotinib also qualify for use of alectinib.

Lung cancer is the leading cause of cancer deaths around the world, responsible for claiming more lives than prostate, colon and breast cancer combined. Medications that target the individual characteristics of a patient's disease continue to create new options and hope for those with lung cancer. For example, tumor cells in about 5 percent of lung cancer patients with NSCLC contain the ALK (anaplastic lymphoma kinase) genetic mutation. In patients with metastatic cancer, the disease spreads to new part of the body. For ALK-positive NSCLC metastatic patients, the disease often spreads to the brain.

Many ALK-positive patients benefit from treatments called ALK inhibitors, such as crizotinib which blocks the activity of the ALK protein and can prevent NSCLC cells from growing and spreading. Alectinib is an oral medication that performs similarly. Patients can also develop resistance to ALK inhibitors such as crizotinib, so alectinib gives health professionals a new option to continue to extend their patients' life span. The FDA previously approved ceritinib (Novartis) in the same treatment setting.

"These types of medications that take advantage of a patient's specific genetic mutations are the future of lung cancer treatments and these treatments create a blueprint of how we can turn some cancers into a chronic disease and eventually create a cure," said Fred R. Hirsch, MD, PhD, Professor of Medicine and Pathology at the University of Colorado Cancer Center and School of Medicine and CEO of the IASLC.

Alectinib is the fifth lung cancer treatment approved by the FDA since early October. The others include:

Necitumumab in combination with standard chemotherapy to treat patients with advanced squamous NSCLC who did not previously received systemic therapy;

Two immunotherapy treatments: nivolumab and pembrolizumab;

And osimertinib, a 3rd-generation EGFR TKI.

IASLC lauds FDA approval of alectinib for lung cancer treatment