X7 Research will take part in a CPhi middle east&africa 2018

Dear colleagues!
X7 Research will take part in a CPhi middle east&africa 2018! CPhI Middle East & Africa will be the region’s most comprehensive pharma gathering. Together, with its co-located events ICSE, P-MEC, InnoPack and FDF, will host over 4,000 key visiting pharma suppliers and buyers. With a wide range of exhibitors from all across the entire pharma supply chain, don’t miss out on your chance to participate at this unrivaled meeting point in Abu Dhabi.

This event will be a fantastic opportunity to highlight the region of the wider pharma market and to give foreign companies real exposure to the potential opportunities it offers. API developers finished dosage suppliers, CROs and manufacturers will have the chance to build strong relationships with key regional and local players to encourage local production, as well as to stimulate imports of high quality, effective medicines in the region.

CPhi middle east&africa 2018 

I and II Phases of clinical trials

Clinical trials of drugs are the final stage of a long and laborious process of their development. Clinical trials of drugs before their official authorization for medical use are conducted in 4 stages, traditionally called “Phases of clinical trials.”

I Phase of clinical trials

(clinical pharmacological, biomedical testing)

The first trials in humans of a new drug (active ingredient) with its preliminary evaluation. Usually, such tests are conducted on a small group (up to 100) of healthy volunteers.

At this stage, we study:

  • tolerability of a single dose of the drug
  • pharmacokinetic parameters
  • pharmacodynamic effects

The importance of Phase I clinical trials is to obtain data on the tolerability and safety of the drug in order to decide whether to further develop or discontinue research.

The aim is to obtain preliminary data on the safety and tolerability of the drug, to make a primary characteristic of the pharmacodynamic and pharmacokinetic properties of the drug in humans, and sometimes also to determine the initial efficacy in human trials

Why do healthy volunteers usually participate? Healthy volunteers (usually male, young) are a homogeneous, highly selective, resistant to potential adverse events, a sample from the general population. In addition, volunteers are easier to recruit and observe. Eliminates the ethical problem associated with the appointment of patients with treatment with unproven efficacy.

In the early stages of Phase I trials, the initial dose, multiplicity and route of administration of the drug are usually established in preclinical trials (in laboratory animals). However, due to differences in pharmacokinetics and pharmacodynamics in humans and animals, such doses may require correction.


II Phase of clinical trials

If the drug is safe and well tolerated, the clinical trial goes to Phase II. This phase requires the inclusion of more subjects, but with a disease (or condition) for which (the diagnosis and/or prophylaxis) of which the active ingredient is intended.

Early Phase II trials are often called pilot trials, as the results provide optimal planning for more expensive and extensive Phase III trials.

The goal of Phase II clinical trials is

  • to prove the clinical efficacy of the drug in a certain group of patients
  • assess the short-term safety of the active ingredient
  • determination of the therapeutic dose level of the drug
  • Dosing regimens

Sometimes Phase II clinical trials are divided into Phases IIa and IIb.

Phase IIa

Pilot clinical trials, designed primarily to determine the level of drug safety in patients with a disease or syndrome for which the drug is used.

During Phase IIa, it is necessary to verify

  • activity of the substance under study
  • assess short-term security
  • establish a contingent of patients
  • Dosing Regimen
  • find out the dependence of the effect on the dose
  • determine the criteria for assessing the effectiveness of

Phase IIb

More extensive basic clinical trials (pivotal trials). They are planned to determine both the effectiveness and safety of the drug’s effects on patients.

The main objective of Phase II6 is to determine the optimal dose level of the drug in order to continue its study in Phase III clinical trials.

Phase II trials are the most important step necessary to decide whether to continue developing a new drug.

Such tests imply the existence of a planned design, clear inclusion/exclusion criteria, randomization, dazzling, follow-up procedures. In other words, such studies are methodologically similar to Phase III trials.

Cardio drug Bayer and J & J fails in attempts to expand indications for use

The company’s Bayer and Johnson & Johnson campaigns to expand the market for Xarelto cardioplasm failed after a potentially new subgroup of patients showed no statistically significant benefits, Reuters reported.

Recall that the anticoagulant Xarelto – one of the most successful drugs J & J, which brought this company about $ 2 billion in 2017, having about 17% of the market share. It is an oral anticoagulant. Widely used to prevent blood clotting. Originally developed by Bayer. In the United States, it is sold by the company Janssen Pharmaceuticals. This is the first available active direct factor Xa inhibitor of oral administration.

According to the New England Journal of Medicine, the Xarelto anticoagulant has not demonstrated the ability to reduce the incidence of the formation of dangerous thrombi in a particular group of patients at high risk of thrombosis after discharge from the hospital.
Participants in the Mariner study were previously hospitalized due to a number of conditions associated with a high risk of venous thromboembolism, such as heart failure, ARI, ischemic stroke, or infectious diseases.

Diseases of the cardiovascular system remain the leading cause of death in many countries of the world. Annually in the world of diseases of the cardiovascular system, 17 million people die. According to the Centers for Disease Control and Prevention, the average life expectancy would be 10 years longer in the absence of such a high prevalence of cardiovascular diseases (CVD), covering all countries and continents. They lead to a long-term disability of the adult contingent of the population and require colossal economic costs. Forecasts of the World Health Organization (WHO) are not optimistic: by 2020, about 20 million people will die from CVD, mainly from heart disease and stroke, which are projected to remain the single leading causes of death. In Russia, since 2000, 2.3 million people die annually from CVD. In terms of 100 thousand population – 2 times more than in Europe and the US, 1.5 times more than the world average.

Link: pharmvestnik.ru

Experimental immunotherapy treatment resulted in complete long remission of advanced breast cancer

There has recently been published a case study from an ongoing clinical study where an experimental immunotherapy treatment was tested. A patient, a 49-year-old woman with advanced breast cancer was told that she had only 3 months to live when she was included in the study. After several weeks of experimental treatment, her tumors disappeared. She has been in complete remission for already 22 months.

This treatment is a modified version of adoptive immunotherapy. Its technique implements harvesting patient’s immune cells – tumor-infiltrating lymphocytes. After been collected from the patient cancer-recognizing molecules are put onto tumor-infiltrating lymphocytes to make them able to find and destroy cancer cells. After that, the cells are transferred back into the patient’s body.

The results of this kind of immunotherapy have been inconsistent in early clinical trials as it showed high efficacy in some patients with certain types of cancers but much less effective in other cases. Especially this experimental treatment was not effective in common epithelial cancers probably due to the low level of mutations in these cancer cells.

This technique also includes sequencing the DNA and RNA from a patient’s tumor in order to find the specific mutations which are unique for this tumor as these mutations are the targets for lymphocytes. The tumor-infiltrating lymphocytes extracted from a patient are tested against thee particular mutations to detect lymphocytes which specifically identify and attack these mutations.

After the most effective lymphocytes are found they are then replicated to get a big number of them and infuse into the patient’s body. After the immune cells were infused back into the patient’s body in this trial the tumors began to disappear fairly fast. Judy Perkins, the patient in the study, recently has given the interview to the BBC, “About a week after [the therapy] I started to feel something, I had a tumor in my chest that I could feel shrinking. It took another week or two for it to completely go away.”

Steven Rosenberg, a leader of this ongoing clinical study, thinks this is a promising early result, indicating that this type of treatment can be applied to a wide variety of different kinds of cancers: “All cancers have mutations, and that’s what we’re attacking with this immunotherapy. It is ironic that the very mutations that cause cancer may prove to be the best targets to treat cancer.”

Link: www.nature.com

Surrogate endpoints approved by FDA

FDA has published a table of surrogate endpoints which may be used by drug developers as primary efficacy clinical trial endpoints for approval of new drug applications (NDAs) or biologics license applications (BLAs). This table reflects the requirement of the 21st Century Cures Act which demanded to publish a list of “surrogate endpoints which were the basis of approval or licensure (as applicable) of a drug or a biological product” for both accelerated and traditional approval provisions.

Therefore, this table provides drug developers with beneficial information on surrogate endpoints which may be adopted for conducting clinical trials after discussing them with FDA on the individual basis.

In concordance with the section 507(e)(9) of the Food, Drug, and Cosmetic (FD&C) Act, the term ‘surrogate endpoint’ means a marker, such as a laboratory measurement, radiographic image, physical sign, or another measure, that is not itself a direct measurement of clinical benefit, and

  • ‘is known to predict clinical benefit and could be used to support traditional approval of a drug or biological product;
  • is reasonably likely to predict clinical benefit and could be used to support the accelerated approval of a drug or biological product in accordance with section 506(c).’

This table includes surrogate endpoints which have already been used by sponsors as primary efficacy clinical trial endpoints for approval of NDAs and BLAs. However, endpoints which have never been used before but according to FDA may be appropriate for use as a primary efficacy clinical study endpoint for drug or biologic approval were also included. The acceptability of using each surrogate endpoint will be considered individually on a case-by-case basis. To sum up, these data were published by FDA in order to facilitate any further drug or biologics license applications.


Link: www.fda.gov

Ketamine study was stopped due to ethical reasons

The advocacy group Public Citizen supported by many bioethics specialists has lodged a complaint against investigators at the Hennepin County Medical Center in Minneapolis to the FDA and Office for Human Research Protections. Two studies conducted in that center involved the use of ketamine or other sedative drugs by paramedics for prehospital agitation.

Usually, the investigators must get the approval of an Institutional Review Board (IRB) to conduct any clinical study. What’s more one of the mandatory documents is the informed consent form which must be signed and dated by patients participating in trials with the exception of emergency cases. However, in this particular study IRB stated that there is no need for the consent and receiving these drugs associated with “minimal risk” both for study participants and for any patients who were prescribed with the same medication.

During the 1st study “profoundly agitated” patients were administered either haloperidol (antipsychotic drug) or ketamine which is also known as a “date rape” drug because after taking it people may experience memory blackouts. The choice of the medicine to be prescribed was not based on clinical considerations but only on the study protocol according to which all patients should take haloperidol during the first 3 months of the trial, ketamine in the next 6 months, then haloperidol in the last 3 months of the trial.

All in all, between October 2015 and September 2016, 146 patients were enrolled into the study and received the treatment according to the protocol. It was found out that severe side effects were observed much more frequently when patients were taking ketamine (49% compared to 5% for haloperidol treatment). What’s more, patients who were receiving ketamine required intubation due to breathing difficulty (39% versus 4% for haloperidol-treated patients).

Despite the fact that it was evident that ketamine treatment was associated with much more safety concerns investigators in the Hennepin County Medical Center moved on to the second study, in the framework of which they compared the efficacy of ketamine treatment with the efficacy of midazolam treatment. They have included 146 subjects during the first year of the study and planned to include 420 patients during the second one. The second study along with the first one was open-label and not randomized. Therefore, during the second study subjects administered one of two doses of ketamine, depending on their agitation level in the first 6 months.

However, the study was stopped on June 25 after the Minneapolis Star Tribune has published an article denouncing the fact that even those patients who were not severely agitated or already restrained kept taking ketamine. Journalists suggested that it was done at the urging of police. They have also exposed one fact when a paramedic gave an injection of ketamine to a woman who had asked for an asthma pump. All these complaints were confirmed by the report from Office of Police Conduct Review, a division of the city’s Department of Civil Rights.


New study finds fake, low-quality medicines prevalent in the developing world

A new study from the University of North Carolina at Chapel Hill found that substandard and falsified medicines, including medicines to treat malaria, are a serious problem in much of the world. In low- and middle-income countries, more than 13 percent of the essential medicines that satisfy the priority health care needs of the population fall in this category. When looking specifically at African countries, the portion of substandard and falsified medicines rises to almost 19 percent.

Falsified medicines are medical products that deliberately and fraudulently misrepresent their identity, composition or source. Substandard medicines are real medical products that fail to meet quality standards or specifications for a variety of reasons, including poor manufacturing, shipping or storage conditions, or because the drug is sold beyond its expiration date.

Researchers analyzed 96 previous studies of falsified and substandard medicines and each of the studies tested more than 50 medications. The team found that antimalarials and antibiotics were the medicines most commonly sold in substandard or falsified conditions. In low- and middle-income countries, 19 percent of antimalarials and 12 percent of antibiotics are substandard or falsified.

Sachiko Ozawa, an associate professor at the UNC Eshelman School of Pharmacy, led the research along with collaborators. The paper published in the journal JAMA Network Open on August 10.

“The prevalence of substandard and falsified medicines is a substantial public health problem because these medicines can be ineffective or harmful and can prolong illnesses, cause poisoning or lead to dangerous drug interactions,” said Ozawa. “Our study shows that a concerted global effort is needed to improve supply chain management for medicines and to identify solutions to this understudied issue.”

The researchers searched five databases for studies related to substandard and falsified medicines. They reviewed 256 studies and included 96 studies in their analysis.

“We need more global collaboration to implement laws on drug quality, increase quality control capacity, and improve surveillance and data sharing,” said James Herrington, a professor in the UNC Gillings School of Global Public Health and a co-author of the study. “This can strengthen the global supply chain against poor quality medicines, improve health outcomes by reducing antimicrobial and anti-parasitic resistance and, ultimately, help governments, businesses and patients save money.”

The team’s analysis found limited information on the economic impact of poor quality medicines, with the estimates of market size ranging widely from $10 billion to $200 billion. Substandard and falsified medicines can burden health systems by diverting resources to ineffective or harmful therapies and cause additional treatment costs and reduced worker productivity due to treatable illnesses, but these effects have not been measured.

Link: www.sciencedaily.com

Mushrooms of the Far East hold promise for the anti-cancer therapy

Mushrooms from the Far East area contain the natural chemical compounds, which could be used for the design of the novel drugs with highly specific anti-tumor activities and low-toxicity. These compounds may offer new avenues for oncology, providing us with either stand-alone alternatives to chemotherapy, chemopreventive medicines, or drugs to be used in combination with other therapies.

The international team of scientists from the Far Eastern Federal University (FEFU), University of Lausanne, and Federal Scientific Center of the East Asia Terrestrial Biodiversity FEB RAS describes the available body of research on four fungi species with high anti-cancer potential. The article is published in Oncotarget and contains the list of tumors, which were reported to be promising targets of the fungal compounds. Among them sarcoma, leukemia, rectum and colon cancer, stomach cancer, liver cancer, colon carcinoma and others.

For the purpose of the current study scientists chose mushrooms widely used in Asian and Far Eastern folk medicine: Fomitopsis pinicola, Hericium erinaceus, Inonotus obliquus, and Trametes versicolor. These species of fungi were shown to selectively target certain malignant tumors. The desired effect is achieved thanks to the various bioactive compounds contained in the mushrooms: polyphenols, polysaccharides, glucans, terpenoids, steroids, cerebrosides, and proteins. These substances are not only capable to hit different critical targets within cancer cells levels but also in certain cases to synergistically boost the chemo. Scientists emphasize that four species of fungi were chosen due to the fact that their medicinal properties are relatively well described. Some of them are already actively used for the anti-cancer drugs manufacturing in certain countires. Undoubtedly, there are many other species of fungi that contain chemical compounds to defeat cancer cells.

“In ancient China mushrooms were considered as the most effective treatment for the various types of tumors. Contemporary fungotherapy (treatment by means of mushrooms) represents a promising field for scientific research. The natural chemical compounds contained in fungi have a huge therapeutic and particularly the anti-cancer potential that has not been yet fully studied”, says Professor Vladimir Katanaev, Dr.Habil, Ph.D., Head of the Laboratory of Pharmacology of Natural Compounds of the Department of Pharmacology and Pharmacy of the School of Biomedicine, FEFU.

Another co-PI and corresponding author of this work, director of the center for genomic and regenerative medicine of the School of Biomedicine, FEFU, Alexander Kagansky, notes that despite that the interest in mushrooms studying has been growing exponentially over the past 60 years, about 90% of the fungal species have never been analyzed for their antibiotic and antitumor activities.

“Moreover, the significant part of cancer-related research of fungi deals merely with their toxicity to cancer cells, and the ability to stop the growth and development of cancer cells. The point is that such properties of the fungi compounds are equally detrimental to the healthy cells of the body”, comments on A. Kagansky. According to the scientist, it is necessary to research fungi for the chemical compounds capable of selective, targeted impact on cancer cells.

Vladimir Katanaev notes the importance of further research the immunomodulatory effect of fungi enriched with polysaccharides. According to him, immunomodulation can be attributed to indirect but effective methods of defeating cancer.

The first generation of natural medical compounds from mushrooms’ extracts wasn’t specific and has been applying widely for the therapy of all cancer types without consideration of tumor type properties. Such therapy damaged not only tumor cells but also healthy cells of the body. There were lots of heavy side-effects at times leading to the death of the patient due to the overdose.

Modern approaches to anti-cancer therapy are based on the targeted treatment with minimal or no consequences to the healthy cells and tissues. For this purpose, not only the general therapeutic properties of fungal chemical compounds are investigated but also the ways they differ in their action on different tumours.

The scientists hope that the high potential of the fungi for the anti-cancer therapy showcased in their article will encourage the further research at the junction of oncology and mycology. Currently in the laboratories of the School of Biomedicine (FEFU) led by Vladimir Katanaev and Alexander Kagansky,the new experiments are conducted to reveal the anti-cancer activities of the mushrooms extracts. This work is aimed at creating the new generation of highly specific low-toxic drugs, which could be specifically targeted on different tumor types.


Link: www.worldpharmanews.com

First EMA publication on the results of transparency policy on the publication of clinical data

The European Medicines Agency (EMA) has recently published the results of their transparency policy on the publication of clinical data which they started implementing almost 3 years ago. According to this policy (Policy 0070), reports on clinical trials where efficacy and safety of new drugs were studied are now open to public including scientists and academics. The Agency have been given the direct access to all reports which were submitted to them as a part of marketing authorisation applications since 1 January 2015.

The published report consists of the data and statistics which cover only one year from 20 October 2016 – a milestone when the EMA’s website on medicines and corresponding clinical data was launched. Therefore, this report contains 54 regulatory dossiers and information on 50 medicines for which dossiers were submitted to the EMA. Amongst these medicines there are orphan, paediatric, biosimilar and generic drugs. The statistics is impressive: there were 80537 of downloads and 22164 document ‘views’ (all for noncommercial objectives).

The report also reveals some information on the overall quantity of published documents and the number of documents which were redacted for the purpose of anonymisation and hiding commercially confidential information (CCI). Interestingly that the EMA has accepted only 24% of CCI redactions proposed by the pharmaceutical companies which led to the fact that only 0,01% of 1,3 million published pages had CCI corrections. The report also tells about the anonymisation techniques which were used to protect CCI and the influence of these techniques on final data quality.

The other part of the statistics is also fairly interesting. The vast majority of users work in the pharmaceutical business, 14% were academics and only 8% of healthcare professional and 8% of ordinary patients accessed this website. The report also analyzes people attitude to the new EMA policy. It turned out that most of the responders totally support it and think that such policy may increase public trust to the EMA activity.

Link: https://clinicaldata.ema.europa.eu/web/cdp/home

The cure for Alzheimer’s is preparing to blow up the market

Chinese scientists from the Ocean University of China, Shanghai Institute of medicine, the Materia Medica at the Chinese Academy of Sciences and of the company Green Valley Pharmaceutical Co., Ltd reported its success in the field of drug creation against Alzheimer’s disease, reports Xinhua. The tool is known as GV-971, and work on it is already 21 years.

The last stage of clinical trials is required before entering the market. It is known that in the study patients were given oral 450 milligrams of GV-971 twice a day for 36 weeks. And the tool significantly improved the condition of people. Experiments with animals were also successful.

The basis of the drug – an extract of brown algae. It can regulate the immune system, reduce inflammation in the nervous system and improve perception. All of this is critical for Alzheimer’s patients. To date, the disease has been diagnosed in approximately 48 million people worldwide. And there is still no effective drug on the market.

Link: http://meddaily.ru/