Tagged: TRI

Takeda Announces Completion of the Post-Marketing Commitment to Submit Data to the FDA, the EMA and the PMDA for Pioglitazone Containing Medicines Including ACTOS

— No overall statistically significant increased risk of bladder cancer in patients ever exposed to pioglitazone in a completed 10-year epidemiological study

OSAKA, Japan, Aug. 29, 2014 /PRNewswire/ — Takeda Pharmaceutical Company Limited (“Takeda”) today announced the completion of the post-marketing commitment and submissions of data from a 10-year epidemiology study to regulatory authorities including the United States (U.S.) Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japanese Ministry of Health, Labour, and Welfare (MHLW) / the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for pioglitazone containing medicines, including ACTOS (pioglitazone HCl).1,2 This study was a 10-year epidemiology study, conducted by the University of Pennsylvania and Division of Research at Kaiser Permanente Northern California (KPNC), and was designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer.1 Findings demonstrate that there is no statistically significant increased risk of bladder cancer among patients ever exposed to pioglitazone.2

The primary analysis found no association between the use of pioglitazone and the risk of bladder cancer.2 Additionally, no association was found between the risk of bladder cancer and the duration of pioglitazone use, increased cumulative dose of pioglitazone or the time since initiating pioglitazone.

In the five-year interim analysis published in Diabetes Care, a statistically significant increased risk among patients who used pioglitazone for two or more years was observed.1 However, the 10-year final analysis did not show any statistically significant findings of increased risk of bladder cancer with long term use of pioglitazone.2 The data will be shared with additional regulatory authorities in accordance with local requirements around the world, and final results will be submitted for publication in 2014.   

“The completion of this long-term study is a milestone in the history of pioglitazone,” said Tom Harris, head, global regulatory affairs, Takeda. “The results of the study provide reassurance with regard to the use of pioglitazone and the risk of bladder cancer and further support the positive benefit risk profile of the product.”

About Pioglitazone

Pioglitazone is approved as an agent to treat patients with Type 2 diabetes mellitus in more than ­­­100 countries world-wide. More than 27,000 subjects have been included in clinical trials, and globally the total patient-years of exposure since first launch (1999) is estimated to be in excess of more than 29 million. Pioglitazone as a treatment of Type 2 diabetes mellitus at the recommended doses provides a valuable treatment option, and has a well established safety profile. The benefits of good glycemic control associated with Type 2 diabetes mellitus outweigh the risks associated with therapy which are appropriately communicated and managed by the current product labelling.

Pioglitazone is a thiazolidinedione for the treatment of Type 2 diabetes in adults as an adjunct to diet and exercise.

Unlike many oral antidiabetic drugs, pioglitazone is not an insulin secretagogue. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism. Therefore, pioglitazone is a medication that depends on the presence of insulin for its mechanism of action, and it decreases insulin resistance in muscle and the liver, resulting in increased insulin-dependent glucose disposal as well as decreased hepatic glucose output.

Clinical studies demonstrate that pioglitazone improves insulin sensitivity in insulin-resistant patients. Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal and improves hepatic sensitivity to insulin. In patients with Type 2 diabetes, the decreased insulin resistance produced by pioglitazone results in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values. In controlled clinical trials, pioglitazone had an additive effect on glycemic control when used in combination with sulfonylurea, metformin, or insulin.

Important Safety Information

Contraindications

Initiation of ACTOS is contraindicated in patients with NYHA Class III or IV heart failure.

ACTOS is contraindicated in patients with known hypersensitivity to pioglitazone or any of its excipients so as to avoid inducing a potentially serious hypersensitivity reaction.

Warnings and Precautions

Fluid retention and cardiac failure: Thiazolidinediones, including ACTOS, can cause dose-dependent fluid retention, which may exacerbate or precipitate heart failure. After initiation of ACTOS, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, discontinuation of ACTOS must be considered. ACTOS should be used with caution in patients with cardiac dysfunction whose physical activity is markedly limited. Combination use with insulin may increase risk.

Hepatic effects: Post-marketing reports of hepatitis and hepatic dysfunction have been received. Very rarely these reports have involved hepatic failure, with and without a fatal outcome, although causality has not been established. Obtain liver tests before starting ACTOS and periodically thereafter. Pioglitazone therapy should not be initiated in patients with increased liver enzyme levels (ALT> 2.5x upper limit of normal) or with any other evidence of liver disease. Existing pioglitazone therapy should be discontinued if ALT levels are persistently higher than 3x the upper limit of normal, and symptoms suggesting hepatic dysfunction should cause the liver enzymes to be checked. Pending the results of laboratory investigations, the decision as to whether pioglitazone therapy should continue must be based on clinical judgment; in the presence of jaundice, drug therapy should be discontinued.

Weight gain: Weight gain was observed in clinical trials and has been seen in post-marketing experience with pioglitazone, so patient weight should be closely monitored.

Fractures: An increased incidence of bone fracture has been noted in female patients.

Bladder cancer: Some data suggest there may be an increased risk of bladder cancer in ACTOS users and also that the risk increases with duration of use. Do not use ACTOS in patients with active bladder cancer. Use caution when using in patients with a prior history of bladder cancer. Tell patients to promptly report any sign of hematuria or other symptoms such as dysuria or urinary urgency as these may be due to bladder cancer.

Hypoglycemia: When ACTOS is used with insulin, a sulfonylurea or other oral hypoglycemic agents, hypoglycemia may occur.

Ovulation: Ovulation in premenopausal anovulatory women or women with polycystic ovarian syndrome may occur with ACTOS.

Macular edema: Post-marketing reports of new-onset or worsening diabetic macular edema with decreased visual acuity have been reported with thiazolidinediones, including pioglitazone. Physicians should consider the possibility of macular edema if a patient reports decreased visual activity.

Drug interactions: Use of ACTOS with CYP2C8 inducers or strong inhibitors may require dose adjustment.

Please refer to the Summary of Product Characteristics (SmPC) for ACTOS before prescribing.

ACTOS should be used according to the indication, posology and method of administration described in the SmPC.

Please consult with your local regulatory agency for approved labeling in your country.

About Type 2 diabetes

  • In 2013, 382 million people worldwide were living with Type 2 diabetes. By 2035 this number is expected to rise to 592 million.3
  • In 2013, the number of people with diabetes in Europe was estimated to be 56 million.4
  • The number of Type 2 diabetes patients is increasing in every country.3
  • In 2013, one in 10 deaths in adults in Europe was attributed to diabetes, representing over 600,000 people.3
  • Estimates indicate that more than EUR 108 billion* was spent on healthcare due to diabetes in the European region in 2013, accounting for over one-quarter of global healthcare expenditures due to diabetes.3
  • Because of the increasingly complex nature of this disease, all patients require treatment to be individualized to their needs.5 Each patient responds differently to medications, and healthcare providers often must combine multiple treatment options to help patients manage their disease.

*Based on conversion of USD 147 billion,3 where 1 EUR = 1.36035 USD as of 21 July 2014.

About Takeda’s Diabetes Business

Takeda’s heritage in diabetes globally includes significant contributions towards scientific discovery and exchange, starting with the discovery of the thiazolidinedione (TZD) pioglitazone, and developments of other fixed-dose combinations. The company’s strong, diverse diabetes portfolio and available medications mark important milestones in Takeda’s ongoing commitment to advancing patient care and helping to meet the individual needs of this growing patient population.

About Takeda Pharmaceutical Company Limited

Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for people worldwide through leading innovation in medicine.

Additional information about Takeda is available through its corporate website, www.takeda.com.

Contact:

Elissa J. Johnsen
+1-224-554-3185  
elissa.johnsen@takeda.com

References

[1] Lewis, JD., Ferrara, A., Peng, T., et al. The Risk of Bladder Cancer Among Diabetic Patients Treated with Pioglitazone: Interim Report of a Longitudinal Cohort Study. Diabetes Care 24, April 2011 34:4 923-929.

[2] Takeda Data on File. 2014. 

[3] International Diabetes Federation. IDF Atlas, sixth edition. Last accessed July 10, 2014. Available at: http://www.idf.org/diabetesatlas.

[4] International Diabetes Federation. Diabetes: Facts and figures. Last accessed July 10, 2014. Available at: http://www.idf.org/worlddiabetesday/toolkit/gp/facts-figures.

[5] Inzucchi SE, Bergenstal RM et al. Management of Hyperglycaemia in Type 2 Diabetes: A Patient-Centred Approach. Diabetes Care. 2012:35: (6):1364-1379.

Coherus Announces CHS-1420 (Investigational Adalimumab Biosimilar) Meets Primary Endpoint In Pivotal Pharmacokinetic Clinical Study

— Company To Pursue Next Stage of Development

REDWOOD CITY, California, Aug. 15, 2014  /PRNewswire/ — Coherus BioSciences, Inc. (“Coherus”) today announced that CHS-1420, its proposed biosimilar of adalimumab (Humira®), met the primary endpoint in a pivotal clinical pharmacokinetic (PK) similarity study that compared CHS-1420 to Humira® in healthy subjects. The parallel-group, single-dose study met the criteria for clinical PK similarity on all three required, prospectively defined, PK endpoints: maximum serum concentration (Cmax), area under the time-concentration curve from first to last time point measured (AUC0-t), and area under the time-concentration curve from first time point extrapolated to infinity (AUC0-inf), with all three geometric mean ratios fully within the 90% confidence interval from 80% to 125%. Both agents were well tolerated and there were no differential safety findings observed between the two agents in this study.

Logo – http://photos.prnewswire.com/prnh/20120507/SF01448LOGO

“An essential global regulatory requirement is the completion of a clinical study directly comparing the originator and our biosimilar candidate establishing PK similarity,” said Barbara Finck, M.D., Chief Medical Officer of Coherus. “We are pleased to have achieved robust results which we believe represents a significant reduction in development program risk.”

“Adalimumab is a very complex molecule. Achieving this clinical milestone further validates Coherus’ development platform and demonstrates our ability to advance biosimilars across our portfolio,” said Denny Lanfear, President and Chief Executive Officer of Coherus.

About Coherus BioSciences, Inc.
Coherus is a late-stage clinical biologics platform company focused on the global biosimilar market. Headquartered in the San Francisco Bay Area and composed of a team of industry veterans with decades of experience in pioneering biologics companies, our goal is to become a global leader in the biosimilar market by leveraging our team’s collective expertise in key areas such as process science, analytical characterization, protein production and clinical-regulatory development. Coherus’ commercialization partnerships include global pharmaceutical companies in Europe, Asia and Latin America.

Biosimilars are intended for use in place of existing, branded biologics to treat a range of chronic and often life-threatening diseases, with the potential to reduce costs and expand patient access. For additional information, please visit www.coherus.com.

Coherus BioSciences Contact
Beth Jimison
+1-650-649-3526
bjimison@coherus.com

Merck Serono Initiates Phase II Study of Anti-PD-L1 Antibody MSB0010718C in Metastatic Merkel Cell Carcinoma

DARMSTADT, Germany, July 29, 2014 /PRNewswire/ —

  • First patient begins treatment in an international Phase II study investigating the efficacy and safety of MSB0010718C in patients with metastatic Merkel cell carcinoma (mMCC) 
  • mMCC is a rare and aggressive skin cancer lacking effective treatments  
  • MSB0010718C is also currently being explored in a seven cohort Phase I clinical trial for the treatment of solid tumors that aims to recruit 590 patients 

Merck Serono, the biopharmaceutical division of Merck, today announced the initiation of an international Phase II study designed to assess the efficacy and safety of MSB0010718C, an investigational fully human IgG1 monoclonal antibody that binds to programmed death-ligand 1 (PD-L1). This multicenter, single-arm, open-label study is being conducted in patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive type of skin tumor,[1],[2] who have previously received one line of chemotherapy. It is expected to recruit 84 patients across Asia Pacific, Australia, Europe and North America. The primary endpoint of the study is overall response.

The PD-L1/PD-1 pathway is implicated as a major mechanism by which tumors evade elimination by the immune system.[3] The PD-L1 molecule is expressed in many cancer types, including mMCC.[3],[4] MSB0010718C, which blocks the interaction of PD-L1 with its receptor PD-1, may have the potential to restore effective anti-tumor T-cell responses and thereby to inhibit tumor growth.

Immune mechanisms are implicated in the pathogenesis of MCC, with an increased risk observed in immunosuppressed individuals.[5] MCC also is associated with the presence of the Merkel cell polyomavirus, which may have a role in tumor formation.[6] Globally, the incidence of MCC is increasing, and outcomes for patients with this disease are poor.[1],[2] Therefore, new treatment approaches are required to improve the outcome of patients with this type of cancer.

“We believe that modulating the immune system by targeting PD-L1 represents a promising new approach in the treatment of this aggressive cancer, especially considering that many of the predisposing factors for mMCC seem to be related to functional disruptions of the immune system,” said Helen Sabzevari, Senior Vice President of Immuno-Oncology at Merck Serono. “Our anti-PD-L1 compound may present a potential new approach for the treatment of mMCC patients. The initiation of this Phase II study is an important milestone, as we endeavor to help those suffering from mMCC, a devastating disease with significant unmet need.”

In addition to this new study in mMCC, MSB0010718C is currently being explored in a Phase I clinical trial for the treatment of solid tumors. The study aims to recruit 590 patients and has enrolled 422 patients to date. On June 1, 2014, Merck Serono presented initial data from this dose escalation study in solid tumors at the annual American Society of Clinical Oncology (ASCO) meeting in Chicago.[7] This study is currently recruiting patients into expansion cohorts in seven cancer types: castrate-resistant prostate cancer, colorectal cancer, gastric/gastroesophageal cancer, melanoma, metastatic breast cancer, non-small cell lung cancer and ovarian cancer.

References 

  1. Hughes MP, et al. Curr Dermatol Rep 2014;3:46-53.
  2. Kaae J, et al. J Natl Cancer Inst 2010;102(11):793-801.
  3. Lipson EJ, et al. Cancer Immunol Res 2013;1(1):54-63.
  4. McDermott DF and Atkins MB. Cancer Med 2013; 2(5):662-73.
  5. Bhatia S, et al. Curr Oncol Rep 2011;13(6):488-97.
  6. Feng H, et al. Science 2008;319(5866):1096-100.
  7. Heery CR, et al. J Clin Oncol 2014;32:5(Suppl.) Abstract No. 3064.

About MSB0010718C 

MSB0010718C is an investigational fully human IgG1 monoclonal antibody that binds to the PD-L1 (programmed death-ligand 1) protein, which is present at high levels in many cancer types. By competitively blocking the interaction with PD-1 receptors, it is believed that MSB0010718C thereby restores anti-tumor T-cell responses.

About Merkel cell carcinoma (MCC) 

MCC is a rare and aggressive disease in which cancer cells form in the top layer of the skin, close to nerve endings. MCC, which is also known as neuroendocrine carcinoma of the skin or trabecular cancer, often starts in those areas of skin that are most often exposed to the sun, including the head and neck, arms, legs, and trunk. Risk factors for MCC include sun exposure and having a weak immune system (i.e., solid-organ transplant recipients, people with HIV/AIDS and people with other cancers, such as chronic lymphocytic leukemia, are at higher risk). Caucasian males over age 50 are at increased risk.

MCC tends to metastasize at an early stage, spreading initially to nearby lymph nodes, and then potentially to more distant areas in the body, including other lymph nodes or areas of skin, lungs, brain, bones, or other organs.

Current treatment options for MCC include surgery, radiation and chemotherapy. Treatment for metastatic or Stage IV MCC is generally palliative.

About Merck Serono 

Merck Serono is the biopharmaceutical division of Merck. With headquarters in Darmstadt, Germany, Merck Serono offers leading brands in 150 countries to help patients with cancer, multiple sclerosis, infertility, endocrine and metabolic disorders as well as cardiovascular diseases. In the United States and Canada, EMD Serono operates as a separately incorporated subsidiary of Merck Serono.

Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. We have an enduring commitment to deliver novel therapies in our core focus areas of neurology, oncology, immuno-oncology and immunology.

For more information, please visit http://www.merckserono.com.

All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to http://www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

Merck is a leading company for innovative and top-quality high-tech products in the pharmaceutical and chemical sectors. With its four divisions Merck Serono, Consumer Health, Performance Materials and Merck Millipore, Merck generated total revenues of € 11.1 billion in 2013. Around 38,000 Merck employees work in 66 countries to improve the quality of life for patients, to further the success of our customers and to help meet global challenges.

Merck is the world’s oldest pharmaceutical and chemical company – since 1668, the company has stood for innovation, business success and responsible entrepreneurship. Holding an approximately 70% interest, the founding family remains the majority owner of the company to this day.

Merck, Darmstadt, Germany is holding the global rights to the Merck name and brand. The only exceptions are Canada and the United States, where the company is known as EMD.

Canola Oil Helps Control Blood Glucose in People with Type 2 Diabetes

WINNIPEG, Manitoba, July 24, 2014 /PRNewswire/ — Canola oil can help control blood glucose (blood sugar) in people with type 2 diabetes when included as part of a low-glycemic index (GI) diet, according to research presented at the June 2014 American Diabetes Association Scientific Sessions (abstract CT-SY24) and published in the peer-reviewed journal Diabetes Care. The study of Canadian adults with type 2 diabetes shows that adding canola oil to the diet is a simple way of helping control blood glucose and risk of cardiovascular disease (CVD). Diabetes affects about 3.3 million Canadians (9 percent) and 26 million Americans (8.3 percent).

In the multicenter, randomized controlled trial, 141 participants with type 2 diabetes who were taking drugs to control blood glucose were given either a test or control diet for three months. The test diet was low GI (minimizes fluctuations in blood glucose levels) and higher in fat, including bread made with canola oil (31 grams of oil per person per day). The control diet was healthy, low-fat and high-fiber, emphasizing whole wheat foods. Results showed that those who consumed the canola oil diet improved blood glucose control. Importantly, participants at increased risk for adverse effects from type 2 diabetes, such as those with high blood pressure, derived the greatest benefits. 

“This study shows the advantage of using canola oil in type 2 diabetes to improve both blood cholesterol and blood glucose control by reducing the glycemic load (GI multiplied by the amount of carbohydrate in the diet), especially in those at highest risk of diabetes complications,” says lead researcher David J.A. Jenkins, M.D., Ph.D., DSc., professor and Canada Research Chair in Nutrition and Metabolism, Department of Nutritional Sciences, University of Toronto as well as director, Risk Factor Modification Center, St. Michael’s Hospital. “These findings are timely since diabetes is expected to double in the next 20 years and means of preventing it and its complications are major concerns of governments and the general public.”

Beyond its results, the “Effect of Lowering the Glycemic Load with Canola Oil on Glycemic Control and Cardiovascular Risk Factors: A Randomized Controlled Trial” is important because it’s the first study to assess the combination of healthy fat consumption and a low-GI diet. The beneficial health effects of canola oil and its fat components (e.g., monounsaturated and omega-3 fats) have been independently shown in other studies.

In addition, even though study participants were being treated with drugs to control blood glucose and had low “bad” LDL cholesterol levels, canola oil consumption was associated with a significant, additional reduction in this type of cholesterol. This may translate into an extra 7 percent reduction in CVD events, Jenkins notes.

“The ability of canola oil to help control blood glucose in people with type 2 diabetes adds to existing evidence of several health benefits, including CVD risk reduction,” adds Shaunda Durance-Tod, M.Sc., R.D., CanolaInfo manager, Canola Council of Canada. “Further studies are now warranted on the effect of canola oil in a Mediterranean-type diet on glycemic control, blood fats and weight loss in type 2 diabetes.”

The canola oil study was led by the University of Toronto in collaboration with the University of Saskatchewan, McMaster University and University of Ottawa. It was funded by the Government of Canada and Canola Council of Canada.