Today, Merck & Co. and Pfizer Inc. announced that they have entered into a worldwide collaboration agreement for the development and commercialization of Pfizer’s ertugliflozin for treatment of type 2 diabetes.

The collaboration for ertugliflozin (PF-04971729) is a worldwide agreement, except in Japan. The investigational oral sodium glucose cotransporter (SGLT2) inhibitor is Phase III ready, and trials are expected to begin later this year.

“We are pleased to join forces with Merck in the battle against type 2 diabetes and the burden that it poses on global health,” John Young, President and General Manager, Pfizer Primary Care said in a statement. “Through this collaboration, we believe we can build on Merck’s leadership position in diabetes care with the introduction of ertugliflozin, an innovative SGLT2 inhibitor discovered by Pfizer scientists.”

According to the agreement, Merck and Pfizer will collaborate on the clinical development and commercialization of ertugliflozin and ertugliflozin-containing fixed dose combinations with metformin and Januvia (sitagliptin) tablets. Merck will continue to retain the rights to its portfolio of sitagliptin-containing products that currently exist. Pfizer has received an upfront payment and milestones of $60 million. Pfizer will also be eligible for additional payments for achieving pre-specified future clinical, regulatory, and commercial milestones. According to the deal, Merck and Pfizer will share potential revenues and certain costs on a 60/40 percent basis.

“Merck continues to build upon our leadership position in the oral treatment of type 2 diabetes through our own research and business development,” Nancy Thornberry, Senior Vice President and Diabetes and Endocrinology Franchise Head, Merck Research Laboratories stated. “We believe ertugliflozin has the potential to complement our strong portfolio of investigational and marketed products, and we look forward to collaborating with Pfizer on its development.”

Source: Pfizer Inc.

Last Updated: 4/29/13; 2:25PM EST

Today, Eli Lilly and Company announced positive results for two additional Phase III studies for its investigational type 2 diabetes drug.

The long-acting glucagon-like peptide 1 (GLP-1) receptor agonist as a once-daily treatment for type 2 diabetes patients met its primary efficacy endpoints of non-inferiority to insulin glargine, which is measured by the reduction of hemoglobin A1c (HbA1c) levels at the 1.5 mg dose. This primary endpoint was met in both AWARD-2 and AWARD-4. Since non-inferiority criterion was met, superiority testing was performed. Results from AWARD-2, show that dulaglutide 1.5 mg dose demonstrated statistically superior reduction in HbA1c from baseline compared to insulin glargine at 52 weeks in patients with type 2 diabetes on metformin and glimeperide. Results from AWARD-4, show that the 1.5 mg dose in combination with insulin lispro demonstrated statistically superior reduction in HbA1c from baseline compared to insulin glargine in combination with insulin lispro at 26 weeks.

The most common adverse events reported from the two studies were gastrointestinal-related, which are consistent with prior studies of the investigational drug.

Lilly previously announced results from the three other Phase III studies AWARD-1, AWARD-3, and AWARD-5. In October 2012, Lilly announced that the primary efficacy endpoints were met in all three studies. According to the company, AWARD studies 1-5 will support registration filings of dulaglutide.

“Dulaglutide, if approved, further advances our efforts to offer a broad portfolio of therapies for people with diabetes, many of whom have unique needs,” Enrique Conterno, President of Lilly Diabetes stated. “The results of our Phase III dulaglutide trials are encouraging and we look forward to sharing more details on the AWARD studies at upcoming scientific meetings.”

According to Lilly, the company expects to submit the investigational drug to regulatory authorities this year.

Source: Eli Lilly and Company

Last Updated: 4/16/13; 3:15PM EST

The Food and Drug Administration (FDA) recently announced that it will be holding a meeting in June to reassess the safety of GlaxoSmithKline Plc (GSK)’s diabetes drug, Avandia.

The best-selling diabetes pill was pulled off the market in Europe and has been tightly restricted in the US because of its association with heart risks. The agency posted a notice on the federal register that a two-day, joint meeting will be held on June 5-6 with two advisory committees to discuss results of a new and independent review of a previous clinical trial. The Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee will discuss results of the RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) trial.

The Committees will provide advice and recommendations to the agency on FDA’s regulatory issues after the RECORD study found that Avandia more than doubled the risk of heart failure, without increasing hospital stays or death from cardiovascular disease. According to Mary Ann Rhyne, a GSK spokeswoman, a new analysis from the study that followed patients for five years did not show a statistically significant different in heart safety between Avandia and older diabetes drugs.

GSK commented that the study showed the drug was as safe as other diabetes drugs; however some FDA scientists believe the study was unreliable due to underreported heart attacks and other problems. The agency determined that patients who can take the drug should be severely limited since the potential risk of heart attack and stroke outweighed the drug’s benefits. Currently, Avandia is only available to patients who sign a waiver from their physician indicating that they understand risks associated with the drug and have tried other drugs to treat their disease.

The reassessment of the drug could change the way Avandia is handled. GSK has already paid over $3 million to settle claims that the company illegally marketed the drug by failing to report safety problems.

Source: Food and Drug Administration 

Last Updated: 4/15/13; 12:00PM EST

RARITAN, N.J., March 29, 2013 – Janssen Pharmaceuticals, Inc. announced today the U.S. Food and Drug Administration (FDA) has approved INVOKANA™ (canagliflozin) for the treatment of adults with type 2 diabetes. INVOKANA™ is the first in a new class of medications called sodium glucose cotransporter 2 (SGLT2) inhibitors to be approved in the United States. It is also the only oral, once-daily medication available in the United States offering improved glycemic control while also showing reduced body weight and systolic blood pressure in clinical trials.

“Patients with type 2 diabetes struggle managing their blood sugar, and nearly half of adults with type 2 diabetes do not achieve recommended levels of glucose control, increasing their risks for potentially life-threatening complications,” said Richard Aguilar*, M.D., Medical Director, Diabetes Nation, LLC and Diabetes Care Foundation, a non-profit organization committed to improving diabetes care.

"INVOKANA™ is thought to work differently than other currently-available medicines because it reduces blood glucose by acting on the kidneys as a ‘glucuretic,’ increasing the loss of glucose in the urine. What has historically been viewed as a sign of diabetes – glucose in the urine – may also reflect the efficacy of a new and unique approach to treatment.”

The kidneys make an important contribution to balancing blood glucose. As glucose is filtered from the blood into the kidneys, it is reabsorbed back into the bloodstream. An important carrier responsible for this reabsorption is called sodium glucose co-transporter 2 (SGLT2). INVOKANA™ selectively inhibits SGLT2, and as a result promotes the loss of glucose in the urine, lowering blood glucose levels in adults with type 2 diabetes.

“INVOKANA™ provides patients with type 2 diabetes the option of a once-daily oral therapy that offers improved glycemic control and, in Phase 3 studies, showed an incidence of hypoglycemia – low blood glucose – that was lower than with glimepiride and similar to that of sitagliptin,” said Jimmy Ren, Ph.D., Therapeutic Area Lead, Metabolics, Medical Affairs, Janssen Pharmaceuticals, Inc. “In addition, this new treatment option is associated with reductions in body weight and systolic blood pressure.”

INVOKANA™ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. INVOKANA™ has been studied as a single agent (monotherapy), in combination with metformin, and in combination with other glucose-lowering agents, including insulin, in patients who need further glucose control. Results from the Phase 3 studies showed INVOKANA™ was generally well tolerated. The most common adverse events with INVOKANA™ are genital mycotic (fungal) infections, urinary tract infections and increased urination. These specific adverse events were generally mild to moderate in intensity and infrequently led to discontinuation in Phase 3 studies. Overall the rate of discontinuation due to adverse events was 4.3 percent for the INVOKANA™ starting dose of 100 milligrams (mg), 3.6 percent for INVOKANA™ 300 mg and 3.1 percent versus competitors.

INVOKANA™ is an important addition to the comprehensive platform of offerings for patients with diabetes from the Johnson & Johnson Family of Companies. Janssen will partner with other Johnson & Johnson companies focused on diabetes, such as LifeScan, Inc., and Animas Corporation, to bring INVOKANA™ to healthcare professionals treating patients with diabetes.

Janssen also will offer a dedicated INVOKANA™ CarePath support program to patients and caregivers. The program provides important support and information regarding affordable access, adherence and education, thereby helping patients to start and appropriately manage their disease and therapy over time. “We are delighted with the approval of INVOKANA™ because it provides a much-needed, new treatment option to help adults with type 2 diabetes and their physicians manage this disease,” said Kirk Ways, M.D., Ph.D., Development Head, Cardiovascular & Metabolism and Compound Development Team Leader, Canagliflozin, Janssen Research & Development.

The new drug application for INVOKANA™ was based on a comprehensive global Phase 3 clinical program, which enrolled 10,285 patients in nine studies and is one of the largest clinical programs in type 2 diabetes submitted to health authorities to date.

Results from this program showed that the 100 mg and the 300 mg doses of INVOKANA™ improved glycemic control and, in pre-specified secondary endpoints, were associated with significant reductions in body weight and systolic blood pressure. In two studies comparing INVOKANA™ to current standard treatments – one studying sitagliptin and the other studying glimepiride – INVOKANA™ dosed at 300 mg provided greater reductions in A1C levels and body weight than either comparator. A1C is the percent of red blood cell hemoglobin with glucose attached to it and an indicator of average blood glucose over the previous two to three months. In the two studies, the overall incidence of adverse events was similar with INVOKANA™ and the comparators.

In studies of INVOKANA™ as monotherapy or in combination with agents not associated with hypoglycemia (such as metformin or metformin and pioglitazone), the incidence of hypoglycemic episodes were less than 5 percent across the groups (INVOKANA™ 100 mg [3.8 percent], INVOKANA™300 mg [4.3 percent], and placebo [2.2 percent]). There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with INVOKANA™ or any other antidiabetic medication. Additional data are being collected to further characterize the cardiovascular profile of INVOKANA™.

Janssen and its affiliates have rights to INVOKANA™ through a license agreement with Mitsubishi Tanabe Pharma Corporation. Janssen Pharmaceuticals, Inc. and its affiliates have marketing rights in North America, South America, Europe, the Middle East, Africa, Australia, New Zealand, and parts of Asia.

About Type 2 Diabetes

The U.S. Centers for Disease Control and Prevention estimates that nearly 26 million Americans have diabetes, 90 to 95 percent of which is type 2 diabetes. Type 2 diabetes is a chronic condition that affects the body's ability to metabolize sugar, or glucose, and is characterized by the inability of pancreatic beta cell function to keep up with the body's demand for insulin.1 U.S. national data from 2007 to 2010 show that nearly half of adults with type 2 diabetes were not achieving recommended levels of glucose control.²

Approximately 60 percent of patients with type 2 diabetes in the United States are obese, while another 30 percent are overweight. In most people at risk for type 2 diabetes, obesity causes the body to resist the action of insulin, and if the pancreatic beta cell cannot produce enough insulin, hyperglycemia and type 2 diabetes ensue. If left uncontrolled, type 2 diabetes can lead to serious complications; improved glycemic control has been demonstrated to reduce the onset and progression of these complications.¹

References

1 Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011. Available at: http://www.diabetes.org/in-mycommunity/local-offices/miami-florida/assets/files/national-diabetes-fact-sheet.pdf. Accessed January 28, 2013.

2 Casagrande SS, Fradkin JE, Saydah SH, Rust KF, Cowie CC. The prevalence of meeting A1C, blood pressure, and LDL goals among people with diabetes, 1988–2010. Diabetes Care. 2013 Feb 15. Epub ahead of print.