Top 20 World Pharma News of 2016 ! PA...
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Top 20 World Pharma News of 2016 ! PART 3
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FDA approves Roche’s cancer immunotherapy TECENTRIQ (atezolizumab) for people with a specific type of metastatic lung cancer

Roche

Roche

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the U.S. Food and Drug Administration (FDA) approved TECENTRIQ® (atezolizumab) for the treatment of people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has EGFR or ALK gene abnormalities. This approval is based on results from the randomised Phase III OAK and Phase II POPLAR studies. The largest study, OAK, showed that TECENTRIQ helped people in the overall study population live a median of 13.8 months, 4.2 months longer than those treated with docetaxel chemotherapy (median overall survival [OS]: 13.8 vs. 9.6 months; HR = 0.74, 95% CI: 0.63, 0.87). The study enrolled people regardless of their PD-L1 status and included both squamous and non-squamous disease types.”TECENTRIQ is a new option to help people with this type of previously treated metastatic lung cancer, regardless of PD-L1 expression, live longer than chemotherapy,” said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. “TECENTRIQ is the first and only approved cancer immunotherapy designed to target the PD-L1 protein, which may play an important role in the way the medicine works.”

The TECENTRIQ development programme includes more than 15 clinical trials in lung cancer, including seven phase III studies in previously untreated (first-line) lung cancer. These studies are evaluating the use of TECENTRIQ alone or in combination with other medicines.

About the OAK study
OAK is a global, multicentre, open-label, randomised, controlled Phase III study that evaluated the efficacy and safety of TECENTRIQ compared with docetaxel in 1,225 people with locally advanced or metastatic NSCLC whose disease had progressed following previous treatment with platinum-containing chemotherapy, with the primary analysis consisting of the first 850 randomised patients. Patients with both squamous and non-squamous disease were randomised (1:1) to receive either TECENTRIQ administered intravenously at 1200 mg every 3 weeks or docetaxel administered intravenously at 75 mg/m2 every 3 weeks. The co-primary endpoints were overall survival (OS) in all randomised patients (ITT population) and in a PD-L1-selected subgroup in the primary analysis population.

About the POPLAR study
POPLAR is a multicentre, open-label, randomised, Phase II study evaluating the efficacy and safety of TECENTRIQ compared with chemotherapy (docetaxel) in people with previously treated recurrent locally advanced or metastatic NSCLC. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety.

The most common side effects (≥ 20%) in patients with metastatic non-small cell lung cancer were fatigue, decreased appetite, dyspnea (shortness of breath), cough, nausea, musculoskeletal pain, and constipation. Nine patients (6.3%) who were treated with TECENTRIQ experienced either pulmonary embolism (2), pneumonia (lung infection) (2), pneumothorax, ulcer hemorrhage (bleeding ulcer), cachexia secondary to dysphagia, myocardial infarction (heart attack), or large intestinal perforation which led to death. TECENTRIQ was discontinued for adverse reactions in 4 percent (6) of the 142 patients.

About non-small cell lung cancer
Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.

About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, TECENTRIQ may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. TECENTRIQ is currently only approved in the US.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

About personalised cancer immunotherapy (PCI)
The aim of personalised cancer immunotherapy (PCI) is to provide patients and physicians with treatment options tailored to the specific immune biology associated with a person’s individual tumour. The purpose is to inform treatment strategies which provide the greatest number of people with a chance for transformative benefit. In the case of TECENTRIQ, the goal of PD-L1 as a biomarker is to explore PD-L1 expression on tumour cells and tumour infiltrating immune cells and how that correlates with clinical benefit either as a monotherapy or in combination, and across a broad range of tumour types. The Roche PCI research and development programme comprises more than 20 investigational candidates, ten of which are in clinical trials.

PCI is an essential component of how Roche delivers on the broader commitment to personalised healthcare.

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. Twenty-nine medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry eight years in a row by the Dow Jones Sustainability Indices.

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2015 employed more than 91,700 people worldwide. In 2015, Roche invested CHF 9.3 billion in R&D and posted sales of CHF 48.1 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

Global pharmaceutical industry calls on governments to work with them to beat the rising threat of drug resistance

More than 80 leading international pharmaceutical, generics, diagnostics and biotechnology companies, as well as key industry bodies, have come together to call on governments and industry to work in parallel in taking comprehensive action against drug-resistant infections – so-called ‘superbugs’ – with a joint declaration launched today at the World Economic Forum in Davos, Switzerland. The statement sets out for the first time how governments and industry need to work together to support sustained investment in the new products needed to beat the challenges of rising drug resistance.The Declaration on Combating Antimicrobial Resistance – drafted and signed by 85 companies and nine industry associations across 18 countries – represents a major milestone in the global response to these challenges, with commercial drug and diagnostic developers for the first time agreeing on a common set of principles for global action to support antibiotic conservation and the development of new drugs, diagnostics, and vaccines. The industry is calling on governments around the world to now go beyond existing statements of intent and take concrete action, in collaboration with companies, to support investment in the development of antibiotics, diagnostics, vaccines, and other products vital for the prevention and treatment of drug-resistant infections.

In particular, the Declaration supports a continuation of efforts towards improved conservation of antibiotics, including a call for improved uptake of rapid point-of-care diagnostics to improve how antibiotics are prescribed, and changes to incentive structures within health systems that directly reward doctors, pharmacists and veterinarians for prescribing antibiotics in greater volumes.

In what the Review on Antimicrobial Resistance recognises to be a notable step for the industry,the signatory companies call on governments to work with them to develop new and alternative market structures that provide more dependable and sustainable market models for antibiotics, and to commit the funds needed to implement them. These mechanisms are needed to provide appropriate incentives (coupled with safeguards to support antibiotic conservation) for companies to invest in R&D to overcome the formidable technical and scientific challenges of antibiotic discovery and development. These include mechanisms to ensure that, where appropriate, the pricing of antibiotics more adequately reflects the benefits they bring; and novel payment models that reduce the link between the profitability of an antibiotic and the volume sold. An integral part of these models is a reduced need for promotional activity by companies.

As well as calling for continued progress by governments on these fronts, the Declaration sets out a commitment to further action on drug resistance by its signatories, which the Review warmly welcomes. These span across three broad areas:

  • Reducing the development of drug resistance. The companies commit to encouraging better and more appropriate use of new and existing antibiotics, including through work that supports the antibiotic stewardship principles set out by the World Health Organization (WHO) Global Action Plan on antimicrobial resistance (AMR), and via improved education of clinicians. This support extends to promoting more judicious use of antibiotics in livestock, as part of a ‘one health’ approach.
  • Increasing investment in R&D that meets global public health needs. Recognising the need to increase research into new antibiotics, diagnostics, vaccines and other alternative treatments, the companies commit to a continuation and extension of collaborative initiatives between industry, academia and public bodies to improve how R&D in the field is done and provide greater opportunities for the scientific barriers to antibiotic discovery to be overcome.
  • Improve access to high-quality antibiotics for all. In light of the gaps that remain in global access to our existing antibiotics and vaccines, and the importance of ensuring that new generations of products are available to all those who need them, the signatories commit to supporting initiatives aimed at ensuring affordable access to antibiotics in all parts of the world, at all levels of income.

By bringing together such a wide range of companies in this unprecedented way, the Declaration provides a valuable roadmap to guide further collaborative efforts between industry, governments and NGOs in the global fightback against AMR. The Review will continue to work to drive progress towards a series of key international milestones in 2016 – including likely discussions on AMR at the UN General Assembly and as part of China’s G20 programme in the autumn – and in support of progress against the WHO Global Action Plan on AMR.

The Declaration will be updated every two years, to take account of the evolving global landscape of AMR and changing challenges and priorities. It remains open to accept new signatory companies and bodies at any time, with a complete list maintained on the Review on AMR’s website, www.amr-review.org/industry-declaration

13. New drug clears psoriasis in clinical trials

About 80 percent of patients with moderate to severe psoriasis saw their disease completely or almost completely cleared with a new drug called ixekizumab, according to three large, long-term clinical trials led by Northwestern Medicine investigator Kenneth Gordon, MD, professor of Dermatology.The results of these phase III trials were compiled in a paper published in the New England Journal of Medicine.

“This group of studies not only shows very high and consistent levels of safety and efficacy, but also that the great majority of the responses persist at least 60 weeks,” said Gordon, who was first author of the paper.

Affecting about 3 percent of the world’s population, psoriasis is an immune-mediated inflammatory disease that causes itchy, dry and red skin. It is also associated with an increased risk for depression, heart disease and diabetes, among other conditions.

Ixekizumab works by neutralizing a pathway in the immune system known to promote psoriasis.

To test the drug’s efficacy over time – and to help clinicians determine whether its benefits outweigh any risks – the three studies enrolled a total of 3,736 adult patients at more than 100 study sites in 21 countries. All participants had moderate to severe psoriasis, which is defined as covering 10 percent or more of the body. Patients were randomly assigned to receive injections of ixekizumab at various doses or a placebo over a period of more than a year.

The investigators assessed whether the drug reduced the severity of psoriasis symptoms compared to the placebo and evaluated safety by monitoring adverse events. By the 12th week, 76.4 to 81.8 percent of patients has their psoriasis classified as “clear” or “minimal” compared to 3.2 percent of patients on the placebo. By the 60th week, 68.7 to 78.3 percent of patients had maintained their improvement.

“Based on these findings, we expect that 80 percent of patients will have an extremely high response rate to ixekizumab, and about 40 percent will be completely cleared of psoriasis,” Gordon said. “Ten years ago, we thought complete clearance of this disease was impossible. It wasn’t something we would even try to do. Now with this drug, we’re obtaining response levels higher than ever seen before.”

Adverse events associated with ixekizumab included slightly higher rates of neutropenia (low white blood cell count), yeast infection and inflammatory bowel disease compared to the placebo. The safety of therapy longer than 60 weeks will need to be monitored in the future.

The drug has been approved by the Food and Drug Administration since the trials were completed.

This research was funded by Eli Lilly and Company, the manufacturer of ixekizumab. Gordon is a paid consultant for Eli Lilly and Company.

14. New compound shows promise in treating multiple human cancers

A new compound, discovered jointly by international pharmaceutical company Servier, headquartered in France, and Vernalis (R&D), a company based in the UK, has been shown by researchers at the Walter and Eliza Hall Institute and Servier to block a protein that is essential for the sustained growth of up to a quarter of all cancers. 

The research presents a new way to efficiently kill these cancerous cells and holds promise for the treatment of blood cancers such as acute myeloid leukaemia, lymphoma and multiple myeloma, as well as solid cancers such as melanoma and cancers of the lung and breast. It is published online today in the journal Nature.

The Servier compound – S63845 – targets a protein of the BCL2 family, called MCL1, which is essential for the sustained survival of these cancer cells.

Institute scientist Associate Professor Guillaume Lessene, who led the Walter and Eliza Hall Institute’s research team in Melbourne, Australia, said the work provided the first clear preclinical evidence that inhibiting MCL1 was effective in targeting several cancer types.

“MCL1 is important for many cancers because it is a pro-survival protein that allows the cancerous cells to evade the process of programmed cell death that normally removes cancer cells from the body,” Associate Professor Lessene said. “Extensive studies performed in a variety of cancer models have shown that S63845 potently targets cancer cells dependent on MCL1 for their survival.”

The institute team of Associate Professor Lessene worked with haematologist Associate Professor Andrew Wei and Dr Donia Moujalled from The Alfred Hospital and Servier scientists, to demonstrate that not only was S63845 effective against several cancer types, but that it could also be delivered at doses that were well tolerated by normal cells.

Dr Olivier Geneste, Director of Oncology Research at Servier, said this preclinical research represented major findings regarding the druggability of MCL1, a valuable and highly challenging target. “S63845 was discovered through collaboration with the fragment and structure based discovery expertise at Vernalis,” he said. “As part of the ongoing Servier / Novartis collaboration on this target class, clinical development of a MCL1 inhibitor should be launched in the near future.”

Associate Professor Lessene said the research provided further evidence of the usefulness of a new class of anti-cancer drugs called BH3 mimetics. “BH3 mimetics inhibit a group of proteins known as the ‘pro-survival BCL-2 proteins’,” he said. “MCL1 is a member of this protein family, and inhibiting it activates the process of programmed cell death. Walter and Eliza Hall Institute researchers revealed the role of BCL-2 in cancer more than 28 years ago and the essential role of MCL1 for the survival of malignant cells four years ago.”

The research was supported through a research collaboration with Servier and through funding from the National Health and Medical Research Council of Australia, the Leukemia and Lymphoma Society (US), Cancer Council Victoria, the Kay Kendall Leukemia Fund, Victorian Cancer Agency, Australian Cancer Research Foundation, the Victorian Government Operational Infrastructure Scheme and the estate of Anthony Redstone.

The Walter and Eliza Hall Institute is the research powerhouse of the Victorian Comprehensive Cancer Centre, an alliance of leading Victorian hospitals and research centres committed to controlling cancer

15. Nanoparticle-based cancer therapies shown to work in humans

A team of researchers led by Caltech scientists have shown that nanoparticles can function to target tumors while avoiding adjacent healthy tissue in human cancer patients. The findings, published online this week in the journal Proceedings of the National Academy of Sciences, demonstrate that nanoparticle-based therapies can act as a “precision medicine” for targeting tumors while leaving healthy tissue intact.”Our work shows that this specificity, as previously demonstrated in preclinical animal studies, can in fact occur in humans,” says study leader Mark E. Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech. “The ability to target tumors is one of the primary reasons for using nanoparticles as therapeutics to treat solid tumors.”

In the study, Davis and his colleagues examined gastric tumors from nine human patients both before and after infusion with a drug – camptothecin – that was chemically bound to nanoparticles about 30 nanometers in size.

“Our nanoparticles are so small that if one were to increase the size to that of a soccer ball, the increase in size would be on the same order as going from a soccer ball to the planet Earth,” says Davis, who is also a member of the City of Hope Comprehensive Cancer Center in Duarte, California, where the clinical trial was conducted.

The team found that 24 to 48 hours after the nanoparticles were administered, they had localized in the tumor tissues, released their drug cargo, and the drug had the intended biological effects of inhibiting two proteins that are involved in the progression of the cancer. Equally important, both the nanoparticles and the drug were absent from healthy tissue adjacent to the tumors.

The nanoparticles are designed to be flexible delivery vehicles. “We can attach different drugs to the nanoparticles, and by changing the chemistry of the bond linking the drug to the nanoparticle, we can alter the release rate of the drug to be faster or slower,” says Andrew Clark, a graduate student in Davis’s lab and the study’s first author.

Davis says his team’s findings are suggestive that a phenomenon known as the enhanced permeability and retention (EPR) effect is at work in humans. In the EPR effect, abnormal blood vessels that are “leakier” than normal blood vessels in healthy tissue allow nanoparticles to preferentially concentrate in tumors. Until now, the existence of the EPR effect has been conclusively proven only in animal models of human cancers.

“Our results don’t prove the EPR effect in humans, but they are completely consistent with it,” Davis says.

The findings could also help pave the way toward more effective cancer drug cocktails that can be tailored to fight specific cancers and that leave patients with fewer side effects.

“Right now, if a doctor wants to use multiple drugs to treat a cancer, they often can’t do it because the cumulative toxic effects of the drugs would not be tolerated by the patient,” Davis says. “With targeted nanoparticles, you have far fewer side effects, so it is anticipated that drug combination can be selected based on the biology and medicine rather than the limitations of the drugs.”

These nanoparticles are currently being tested in a number of phase-II clinical trials.

In addition to Davis and Clark, other coauthors on the study, entitled “CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing,” include Devin Wiley (MS ’11, PhD ’13) and Jonathan Zuckerman (PhD ’12); Paul Webster of the Oak Crest Institute of Science; Joseph Chao and James Lin at City of Hope; and Yun Yen of Taipei Medical University, who was at City of Hope and a visitor in the Davis lab at the initiation of the clinical trial.

The research was supported by grants from the National Cancer Institute and the National Institutes of Health and by Cerulean Pharma Inc. Davis is a consultant to and holds stock in Cerulean Pharma Inc

COURTESY – WORLD PHARMA NEWS



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