GSK joins with research councils in UK and South Africa to tackle non-communicable diseases

GSK has announced a £5m collaboration with the UK and South African Medical Research Councils, to support much-needed research into non-communicable diseases (NCDs) in Africa, as part of GSK's Africa NCD Open Lab initiative.

The funding was pledged today by the UK Foreign Office Minister responsible for Africa, James Duddridge, and South Africa's Minister for Science and Technology, Naledi Pandor, at an event in Cape Town, South Africa, as part of a broader collaboration between the two countries on scientific research. It will be used to support researchers from South African institutions conducting research projects in NCDs, aligned with the objectives of GSK's Africa NCD Open Lab.

£2.5m will be provided by the UK MRC, via the UK Newton Fund - a government fund established in 2013 to develop science and innovation partnerships that promote the economic development and welfare of developing countries - and approximately £1.5m will come from the South African Medical Research Council. GSK will provide an additional £1m, together with a commitment of internal R&D expertise, to support projects within South Africa. As the first initiative to receive support from the UK / South Africa Newton Fund, this is significant external endorsement for GSK's open approach to NCD research in Africa.

Alongside the funding confirmed today for South African research proposals, GSK will also commit a further £4m to support successful proposals for NCD research from selected countries elsewhere in sub-Saharan Africa. The call for proposals from these countries will launch later in 2014.

The Africa NCD Open Lab was established by GSK earlier this year as part of a series of strategic investments in sub-Saharan Africa. In this region, and across developing countries, non-communicable diseases, such as cancer and diabetes, pose an increasing threat, and more needs to be done to understand the specific variations of disease in this setting. The Africa NCD Open Lab aims to address this through the creation of an innovative research network that will see GSK scientists collaborate with researchers across Africa on high quality epidemiological, genetic and interventional research, from its hub at GSK's Stevenage R&D facility in the UK. The aim is that this will help build local expertise, creating a new generation of African NCD experts, while instilling a deep vein of "African thinking" within GSK's own R&D organisation.

This builds on the success of GSK’s Open Lab in Tres Cantos, Spain, which was established in 2010 to give independent researchers access to GSK facilities, resources and knowledge, to help them advance their own projects in to diseases of the developing world, such as malaria, tuberculosis and leishmaniasis. Since the Tres Cantos Open Lab was established, 14 projects from world class institutions have completed, progressing much needed research into diseases of the developing world.

Patrick Vallance, President of Pharmaceutical R&D at GSK, said: "The funding announced today is a great endorsement of GSK's open research philosophy, and signifies growing agreement among the scientific community that collaboration is key to defeating some of the world's biggest health problems.

"We believe that by providing support to African institutions as they carry out their own research in to the chronic disease variants that most affect the African people, the NCD Open Lab will play a key role in helping to tackle disease in this area."

An official call for proposals, seeking interest from researchers from South Africa and wider sub-Saharan Africa, will be launched later in 2014, to begin in the second quarter of 2015.

GSK - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Strides Arcolab Ltd Bangalore gets USFDA approval for Methoxsalen

strides Arcolab, a successful pharmaceutical organization, has well established itself in India as a producer of specialty generic drugs and biopharmaceutical agents. Apart from these two major categories, Strides has carved a name for itself for being among the world’s biggest manufacturer of soft gelatin capsules. It has also acquired Stelis biopharmaceuticals, which focusses on the development of biosimilars and its supply to the regulated US and European markets.

Based in Bengaluru, this pharma organization boasts of a state of the art manufacturing and research facility in 5 sites across the country, a presence in 75 countries, and an outstanding sales and commercial group to establish business relationships with the world to sell their products.

Their KRS Gardens site is the lead area for the manufacture of oral dosage forms, including capsules and tablets. This site recently was cleared by the USFDA, which now makes it capable of supplying generics and capsule shells to North America.

The latest feather in their cap is the USFDA approval of their Methoxsalen capsules. This product would be made available in 10 mg capsules and produced in the Bengaluru facitlity, which has been cleared by the local and international regulatory bodies.

Methoxsalen is a drug used in the management of skin conditions such as psoriasis, eczema, contact dermatitis and vitiligo. The drug acts best when used along with a secondary means of treatment, such as exposing the affected part of the skin to UV-A light. Different forms of cutaneous lymphomas have also been effectively controlled using Methoxalen, where it functions by altering the biochemical pathways in these damaged cells. Currently, the US drug market for Methoxsalen crosses US $13 million, which thus makes this product very viable in International markets.

 
Needless to say, this is a big move for Strides with a good potential and opportunity to further expand its global presence.

Dr. Jay Shinde

West Pharma ventures into India

he US based West Pharma has been a major player in providing packaging expertise to major pharmaceutical organizations around the globe. Their forte lies in parenteral preparations, container seals and closures for parenteral formulations, and stability testing of the packaged materials. Since its inception in 1923, West has been actively developing premium, yet pharmaceutically acceptable products and packaging materials for medical devices.

West’s most recent foray has been establishing its presence in India, in the city of Chennai. In June 201, they commenced the set-up of their manufacturing plant in Sri City, which was designed to take care of the global packaging material supply. In order to bring this into effect, they signed a 99 year lease, which gave them access to almost 75000 square metres of land in the Special Economic Zone (SEZ) in Southern India. This came with a plethora of privileges in construction, utility management, labor availability, export and import tax reductions, just to name a few. After the completion of the first phase, which began in August 2012, the unit is now operational and capable of producing metallic and elastomeric seals for parenteral/ injectables. Further construction is currently underway, where a ready-to-sterilize range of components would be manufactured in the first quarter of 2016.

Due to a very central location in the Indian subcontinent, the exports of these pharmaceutical seals to various biopharmaceutical customers in India and globally, would be far easier and practical.

The first phase has a built up area of about 15000 square metres, which is steadily on the rise, and upon completion of the functional offices and manufacturing stations, will shoot up to above 37000 square meters. The estimated date for completion of this project is in 2023. In the near future, West will file DMFs for its newly constructed plant with the USFDA and Canadian Pharmaceutical Bureau.

Dr. Jay Shinde

Afrezza (insulin human) inhalation powder, a rapid-acting inhaled insulin to improve glycemic control in adults with diabetes mellitus.

The FDA has approved Afrezza (insulin human) inhalation powder, a rapid-acting inhaled insulin to improve glycemic control in adults with diabetes mellitus. Afrezza is a rapid-acting inhaled insulin that is administered at the beginning of each meal.

An estimated 25.8 million (18.8 million diagnosed and 7.0 million undiagnosed) people in the United States or approximately 8.3 percent of the population–have diabetes. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness and nerve and kidney damage.

Afrezza is a new treatment option for patients with diabetes requiring mealtime insulin. Today’s approval broadens the options available for delivering mealtime insulin in the overall management of patients with diabetes who require it to control blood sugar levels.

The drug’s safety and effectiveness were evaluated in a total of 3,017 participants, 1,026 participants with type 1 diabetes and 1,991 patients with type 2 diabetes. The efficacy of mealtime Afrezza in adult patients with type 1 diabetes patients was compared to mealtime insulin aspart (fast-acting insulin), both in combination with basal insulin (long-acting insulin) in a 24 week study. At week 24, treatment with basal insulin and mealtime Afrezza provided a mean reduction in HbA1c (hemoglobin A1c or glycosylated hemoglobin, a measure of blood sugar control) that met the pre-specified non-inferiority margin of 0.4 percent.

Afrezza provided less HbA1c reduction than insulin aspart, and the difference was statistically significant. Afrezza was studied in adults with type 2 diabetes in combination with oral antidiabetic drugs; the efficacy of mealtime Afrezza in type 2 diabetes patients was compared to placebo inhalation in a 24 week study. At week 24, treatment with Afrezza plus oral antidiabetic drugs provided a mean reduction in HbA1c that was statistically significantly greater compared to the HbA1c reduction observed in the placebo group.

Afrezza is not a substitute for long-acting insulin. Afrezza must be used in combination with long-acting insulin in patients with type 1 diabetes, and it is not recommended for the treatment of diabetic ketoacidosis, or in patients who smoke.

Afrezza has a Boxed Warning advising that acute bronchospasm has been observed in patients with asthma and chronic obstructive pulmonary disease (COPD). Afrezza should not be used in patients with chronic lung disease, such as asthma or COPD because of this risk. The most common adverse reactions associated with Afrezza in clinical trials were hypoglycemia, cough, and throat pain or irritation.

The FDA approved Afrezza with a Risk Evaluation and Mitigation Strategy, which consists of a communication plan to inform health care professionals about the serious risk of acute bronchospasm associated with Afrezza.

The FDA is requiring the following post-marketing studies for Afrezza:

- a clinical trial to evaluate pharmacokinetics, safety and efficacy in pediatric patients;

- a clinical trial to evaluate the potential risk of pulmonary malignancy with Afrezza (this trial will also assess cardiovascular risk and the long-term effect of Afrezza on pulmonary function);

- two pharmacokinetic-pharmacodynamic euglycemic glucose-clamp clinical trials, one to characterize dose-response and one to characterize within-subject variability.

Afrezza is manufactured by MannKind Corporation.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

- Complete and submit the report Online:www.fda.gov/MedWatch/report.htm

- Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

Thoughts health innovators? bit.ly/1vr8vRz

Study finds outcome data in clinical trials reported inadequately, inconsistently

There is increasing public pressure to report the results of all clinical trials to eliminate publication bias and improve public access. However, investigators using the World Health Organization's International Clinical Trials Registry Platform (ICTRP) to build a database of clinical trials involving chronic pain have encountered several challenges. They describe the perils and pitfalls of using the ICTRP and propose alternative strategies to improve clinical trials reporting. This important and insightful study is published in the August issue of the journal PAIN®.

U.S. law already requires posting summarized results on ClinicalTrials.gov, a service of the National Institutes of Health, within one year of study completion for certain categories of industry-sponsored trials. Legislation mandating data publication within one year of study completion, irrespective of outcome, is under consideration in the European Union. Yet compliance with the U.S. law is poor.

"Although clinical trial registries facilitate public access to basic trial information, we found that access to unbiased trial results is still inadequate. A distressingly large number of trials have no published results at all or are mentioned only in sponsor press releases. Recent analyses have found that only 25-35% of clinical trials required to post study results on ClinicalTrials.gov actually do so," comments senior investigator Michael C. Rowbotham, MD, scientific director of the California Pacific Medical Center Research Institute in San Francisco.

The investigators drew on their experience with the Repository of Registered Analgesic Clinical Trials (RReACT) database, a scorecard for analgesic clinical trials for chronic pain (sponsored by an FDA grant to the University of Rochester), to describe the challenge of constructing a global open-access database of clinical trials and trial results. They focused on three frequently studied chronic pain disorders: post-herpetic neuralgia, fibromyalgia, and painful diabetic peripheral neuropathy. The initial build of RReACT was limited to randomized trials registered on ClinicalTrials.gov with a primary (or key secondary) outcome measure assessing analgesic drug efficacy. The database was then expanded to report on all of the primary registries in the ICTRP, and investigators analyzed trial registration, registry functionality, and cross-registry harmonization, using a comprehensive search algorithm to find trial results in the peer-reviewed literature and grey literature. A total of 447 unique trials were identified, with 86 trials listed on more than one registry.

The ICTRP provides a single search portal to 15 primary registries, including ClinicalTrials.gov. ICTRP primary registries follow International Committee of Medical Journal Editors (ICMJE) guidelines and must have a national or regional focus, government support, nonprofit management, free public access, and an unambiguous trial identification method.

ClinicalTrials.gov is the largest ICTRP database, with more than 152,000 trials globally. The EU Clinical Trials Register (EU-CTR) is the second largest, with more than 21,000 trials. Current Controlled Trials (more than 11,000 trials), the oldest global registry, is hosted by BioMed Central (part of Springer Science + Business Media, a for-profit scientific publisher specializing in open-access journals). Five national registries each contain fewer than 1,000 trials. All ICTRP registries provide information about study design (i.e., randomization, blinding, control groups, inclusion/exclusion criteria, and outcome measures) and current study status. Not all ICTRP registries track study changes, list additional study identifiers, or provide links to publications.

"We identified several perils and pitfalls of using the ICTRP," says Dr. Rowbotham. "Manual searches are necessary, as ICTRP does not reliably identify trials listed on multiple registries. Searching ICTRP as a whole yields different results from searching registries individually. Outcome measure descriptions for multiply-registered trials vary between registries. Registry-publication pairings are often inaccurate or incomplete. Ideally, a PubMed search on the trial registration number would reveal all study-related articles, but a recent analysis showed that about 40% of journal publications failed to include registration numbers. And grey literature results--such as trial-specific press releases or company statements, information found on the websites of pharmaceutical companies, and abstracts of poster/platform presentations at scientific meetings--are not permanent.

"Creating a single global registry would solve many of the problems we describe here," he continues. "However, international politics and funding limitations suggest this is a challenging goal. Despite its flaws, ICTRP does at least offer a single search portal."

The investigators offer several suggestions for improving the current situation. In addition to the simple remedy of including trial registration numbers on all meeting abstracts and peer-reviewed papers, they propose specific strategies to identify multiply-registered studies and ensuring accurate pairing of results and publications.

"Compliance might improve, especially for difficult-to-publish 'negative' studies, if posting results on trial registries could be made simpler and uniform. Alternative solutions to the problems of publication bias and selective reporting should also be explored. These might involve including journals specializing in publishing 'negative' results, creating user-friendly and publicly available databases to publish results, and raising the awareness of authors, reviewers, and editors about these issues," concludes Dr. Rowbotham.

Study finds outcome data in clinical trials reported inadequately, inconsistentlyTUESDAY, 20 MAY 2014 E-mailPrintPDFThere is increasing public pressure to report the results of all clinical trials to eliminate publication bias and improve public access. However, investigators using the World Health Organization's International Clinical Trials Registry Platform (ICTRP) to build a database of clinical trials involving chronic pain have encountered several challenges. They describe the perils and pitfalls of using the ICTRP and propose alternative strategies to improve clinical trials reporting. This important and insightful study is published in the August issue of the journal PAIN®.U.S. law already requires posting summarized results on ClinicalTrials.gov, a service of the National Institutes of Health, within one year of study completion for certain categories of industry-sponsored trials. Legislation mandating data publication within one year of study completion, irrespective of outcome, is under consideration in the European Union. Yet compliance with the U.S. law is poor.
"Although clinical trial registries facilitate public access to basic trial information, we found that access to unbiased trial results is still inadequate. A distressingly large number of trials have no published results at all or are mentioned only in sponsor press releases. Recent analyses have found that only 25-35% of clinical trials required to post study results on ClinicalTrials.gov actually do so," comments senior investigator Michael C. Rowbotham, MD, scientific director of the California Pacific Medical Center Research Institute in San Francisco.
The investigators drew on their experience with the Repository of Registered Analgesic Clinical Trials (RReACT) database, a scorecard for analgesic clinical trials for chronic pain (sponsored by an FDA grant to the University of Rochester), to describe the challenge of constructing a global open-access database of clinical trials and trial results. They focused on three frequently studied chronic pain disorders: post-herpetic neuralgia, fibromyalgia, and painful diabetic peripheral neuropathy. The initial build of RReACT was limited to randomized trials registered on ClinicalTrials.gov with a primary (or key secondary) outcome measure assessing analgesic drug efficacy. The database was then expanded to report on all of the primary registries in the ICTRP, and investigators analyzed trial registration, registry functionality, and cross-registry harmonization, using a comprehensive search algorithm to find trial results in the peer-reviewed literature and grey literature. A total of 447 unique trials were identified, with 86 trials listed on more than one registry.
The ICTRP provides a single search portal to 15 primary registries, including ClinicalTrials.gov. ICTRP primary registries follow International Committee of Medical Journal Editors (ICMJE) guidelines and must have a national or regional focus, government support, nonprofit management, free public access, and an unambiguous trial identification method.
ClinicalTrials.gov is the largest ICTRP database, with more than 152,000 trials globally. The EU Clinical Trials Register (EU-CTR) is the second largest, with more than 21,000 trials. Current Controlled Trials (more than 11,000 trials), the oldest global registry, is hosted by BioMed Central (part of Springer Science + Business Media, a for-profit scientific publisher specializing in open-access journals). Five national registries each contain fewer than 1,000 trials. All ICTRP registries provide information about study design (i.e., randomization, blinding, control groups, inclusion/exclusion criteria, and outcome measures) and current study status. Not all ICTRP registries track study changes, list additional study identifiers, or provide links to publications.
"We identified several perils and pitfalls of using the ICTRP," says Dr. Rowbotham. "Manual searches are necessary, as ICTRP does not reliably identify trials listed on multiple registries. Searching ICTRP as a whole yields different results from searching registries individually. Outcome measure descriptions for multiply-registered trials vary between registries. Registry-publication pairings are often inaccurate or incomplete. Ideally, a PubMed search on the trial registration number would reveal all study-related articles, but a recent analysis showed that about 40% of journal publications failed to include registration numbers. And grey literature results--such as trial-specific press releases or company statements, information found on the websites of pharmaceutical companies, and abstracts of poster/platform presentations at scientific meetings--are not permanent.
"Creating a single global registry would solve many of the problems we describe here," he continues. "However, international politics and funding limitations suggest this is a challenging goal. Despite its flaws, ICTRP does at least offer a single search portal."
The investigators offer several suggestions for improving the current situation. In addition to the simple remedy of including trial registration numbers on all meeting abstracts and peer-reviewed papers, they propose specific strategies to identify multiply-registered studies and ensuring accurate pairing of results and publications.
"Compliance might improve, especially for difficult-to-publish 'negative' studies, if posting results on trial registries could be made simpler and uniform. Alternative solutions to the problems of publication bias and selective reporting should also be explored. These might involve including journals specializing in publishing 'negative' results, creating user-friendly and publicly available databases to publish results, and raising the awareness of authors, reviewers, and editors about these issues," concludes Dr. Rowbotham.
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Stem cell research says Schizophrenia begins in womb

Researchers have shown that neurons generated from the skin cells of people with schizophrenia behave unfamiliar in early developmental stages. They used new stem cell research technology for same and they believe that this research may provide new ideas to detect and potentially cure the disease early.

Over 1.1 percent of the world's population has schizophrenia out of which almost three million cases in the US alone. Scientists still know very little about its underlying causes, and it is still unknown which cells in the brain are affected and how. In 2002, Americans spent nearly $63 billion on treatment and managing disability and 10 percent of those with schizophrenia are driven to commit suicide by the burden of coping with the disease.

Prior, researchers had only studied brains of death schizophrenic patients. And it is well known that age, stress, medication or drug abuse had often altered or damaged the brains of these patients which making it more difficult to find out details of disease. But Fred Gage and his team were avoided this problem by taking skin cells from patients and coaxed them to stem cell and encouraged them to grow into very early-stage neurons (dubbed neural progenitor cells or NPCs). These NPCs are same as cells in the brain of a developing fetus.

They generated NPCs from the skin cells of 4 patients with schizophrenia and 6 normal human beings. Then researchers tested the cells in two different assays. In first one, they looked at how far the cells moved and interacted with particular surfaces and in the second one, they looked at stress in the cells by imaging mitochondria.

And in both assays, the team of scientists found that NPCs from people with schizophrenia differed in significant ways from those taken from unaffected people. In particular, cells predisposed to schizophrenia showed unusual activity in two major classes of proteins: those involved in adhesion and connectivity, and those involved in oxidative stress. Neural cells from patients with schizophrenia tended to have aberrant migration (which may result in the poor connectivity seen later in the brain) and increased levels of oxidative stress (which can lead to cell death).
These findings are consistent with a prevailing theory that events occurring during pregnancy can contribute to schizophrenia, even though the disease doesn't manifest until early adulthood. Past studies suggest that mothers who experience infection, malnutrition or extreme stress during pregnancy are at a higher risk of having children with schizophrenia. The reason for this is unknown, but both genetic and environmental factors likely play a role.

Fred H. Gage, Salk professor of genetics, said, "This study aims to investigate the earliest detectable changes in the brain that lead to schizophrenia. We were surprised at how early in the developmental process that defects in neural function could be detected."

Kristen Brennand, the first author of the paper and assistant professor at Icahn School of Medicine at Mount Sinai, said,  "We realized they weren't mature neurons but only as old as neurons in the first trimester. So we weren't studying schizophrenia but the things that go wrong a long time before patients actually get sick."

The findings of the study were published online in April's Molecular Psychiatry, support the theory that the neurological dysfunction that eventually causes schizophrenia may begin in the brains of babies still in the womb.