美国2014年开发中的糖尿病新药

20 14 R EPO RT Nearly 26 million Americans are affected by diabetes—including 7 million people who are unaware they have the disease. One of the top 10 causes of death in the United States, diabetes has far-reaching implications for patients and their fami- lies and our health care system. While healthy eating and exercise can help prevent and manage type 2 diabe- tes, medicines play a key role in helping reduce the risk of and treat the disease. For example, one medicine was found in studies to lower the risk by 31 percent. And in recent years, eight new classes of type 2 diabetes medicines have been ap- proved by the Food and Drug Administra- tion (FDA), giving patients and health care providers powerful new options to treat this chronic and devastating condition. To build on progress to date and help further meet the challenges posed by diabetes, America’s biopharmaceutical research companies are developing 180 new medicines for type 1 and type 2 diabetes and diabetes-related conditions, such as chronic kidney failure due to diabetes and painful diabetic neuropathy. Additionally, there are 200 active dia- betes clinical trials in the United States, including 140 that have not yet started recruiting patients or are just now seek- ing volunteers to participate and another 60 that are active, but not recruiting new patients. In addition to the critical role these trials play in the development and testing of new treatments, they rep- resent potentially valuable therapeutic options for patients battling diabetes and diabetes-related conditions. According to the Centers for Disease Control and Prevention (CDC), death rates for people with diabetes fell sub- stantially—up to 40 percent—between 1997 and 2006. CDC links this decrease to improved cardiovascular medical treatment, better management of diabe- tes, and some healthy lifestyle changes. Unfortunately, while the death rates due to diabetes are declining, the rate of new cases has been rising. The number of Americans diagnosed with diabetes has more than tripled since 1980, according to the CDC. Lifestyle choices can affect this increase. The CDC-led National Diabetes Prevention Program found that Biopharmaceutical Research Companies Are Developing 180 Medicines to Treat Diabetes and Related Conditions MEDICINES IN DEVELOPMENT Diabetes PRESENTED BY AMERICA’S BIOPHARMACEUTICAL RESEARCH COMPANIES Un sp ec ifi ed Di ab et es 30 16 Ty pe 2 Di ab et es Ty pe 1 Di ab et es 100 Di ab et es -R ela te d C on di tio ns 52 Application Submitted Phase III Phase II Phase I Medicines in Development For Diabetes Contents Recent Diabetes Medicine Approvals .......................................2 Diabetes Medicines in the Pipeline ......2 Early Diabetes Breakthroughs ............3 Diabetes Medications— Improving Adherence ...................... 4 Treatment Intensifi cation/ Clinical Inertia .................................5 Facts About Diabetes in the United States ................................. 6 Medicines in Development ................7 Glossary ....................................... 21 Drug Development/ Approval Process ...........................23 Medicines in Development Diabetes 20142 weight loss and increased physical activity in people at high risk for diabetes reduced the development of type 2 diabetes by 58 percent in a three-year period. According to the American Diabetes Association, most Ameri- cans with diabetes have type 2, in which relative insulin defi - ciency combines with the body failing to properly use insulin. Between 5 percent and 10 percent of Americans with diabetes have type 1, in which the body fails to produce insulin. The medicines in the pipeline today offer hope of reducing the human toll and economic costs of diabetes. Examples of some medicines now being tested include: • A medicine that improves glucose-dependent insulin secretion. • A medicine designed to inhibit an enzyme linked to diabetic neuropathy. • A treatment designed to stimulate and enhance the regeneration of insulin-producing cells. While diabetes remains a challenging illness, America’s biophar- maceutical research companies are continuing their efforts to develop novel and more effective therapies to treat the disease and improve the quality of life for diabetes patients. Recent Diabetes Medicine Approvals New medicines approved by the FDA in the last year repre- sent exciting steps forward in efforts to better treat diabetes. These include: • Nesina® (alogliptin) is a new DPP-4 inhibitor designed to slow the inactivation of incretin hormones GLP-1 and GIP, resulting in more active incretins enabling the pancreas to secrete insulin and better managing blood glucose levels. • Invokana® (canaglifl ozin) is the fi rst sodium-glucose co- transporter 2 (SGLT2) inhibitor approved for patients with type 2 diabetes. SGLT2 inhibitors work in conjunction with the kidneys and the natural urination process to remove excess blood glucose from the body. • Duetact® (pioglitazone/glimepiride) combines two previ- ously approved type 2 diabetes medicines with comple- mentary actions in a single tablet. One medicine targets insulin resistance while the other increases the amount of insulin produced by the pancreas. • Farxiga™ (dapaglifl ozin) is a new SGLT2 inhibitor approved to improve glycemic control in adults with type 2 diabetes. Diabetes Medicines in the Pipeline America’s biopharmaceutical research companies continue to explore many different approaches to battle diabetes and related-conditions. Some potential innovations from the 180 medicines in development today, include: Stimulating the Formation of Insulin Producing Cells— A potential fi rst-in-class treatment for type 1 diabetes is designed to stimulate and enhance the regeneration of insulin-producing cells (islets). The treatment is a human peptide consisting of the bioactive part of a gene respon- sible for regenerating pancreatic islets. In diabetes, there are often too few insulin-producing islets to keep up with the demand for insulin. Next-Generation Oral Treatment—A medicine in develop- ment for the treatment of type 2 diabetes is part of the DPP-4 inhibitor class, but chemically distinct from other approved medicines in this class. DPP-4 inhibitors work by stimulating the production of insulin and producing less glu- cose. In clinical trials, the medicine was able to inhibit more than 80 percent of its target enzyme for seven days, making it potentially a once-weekly treatment versus daily. Once-Weekly Treatment—A medicine in development is in the same class of drugs as some other approved medicines for type 2 diabetes, but with a longer therapeutic life that Key Issues Source: PhRMA, 2014 Medicines in Development for Diabetes MEDICINES IN DEVELOPMENT FOR DIABETESMEDICINES IN DEVELOPMENT FOR DIABETES BIOPHARMACEUTICAL RESEARCH COMPANIES ARE DEVELOPING 180 MEDICINES TO TREAT TYPE 1 & TYPE 2 DIABETES INCLUDING FOR DIABETES128 FOR DIABETES-RELATEDCONDITIONS52 – AND – Medicines in Development Diabetes 2014 3 may make it suitable for once-weekly dosing. The medicine is a human glucagon-like peptide (GLP-1) analogue that lowers blood glucose and reduces body weight. Facilitating Glucose Regulation—A potential medicine in development for type 2 diabetes is a gut sensory modulator (GSM) delivered directly to the stomach where it intensifi es the body’s natural food-driven signals that facilitate glucose regulation. The medicine, a delayed-release formulation of metformin (a medicine used to treat diabetes alone or in com- bination with other medicines), targets the lower gut to avoid systemic absorption in the bloodstream, making it potentially useful to diabetes patients with renal impairment who are unable to use metformin due to the risk of building metfor- min up in the blood (lactic acidosis). Painful Nerve Damage—Nerve damage is a common symp- tom of diabetes. About half of all people with diabetes have some form of nerve damage, or neuropathy, according to the American Diabetes Association. Over time, blood glucose can injure the walls of tiny blood vessels that nourish nerves causing pain, especially in the legs. One medicine in develop- ment is designed to improve the symptoms of diabetic neu- ropathy by inhibiting the activity of an enzyme that causes the accumulation of intracellular sorbitol (a sugar alcohol) that causes diabetic neuropathy. Diabetic Kidney Disease—A potential fi rst-in-class medicine is in development for the treatment of diabetic nephropathy —a chronic progressive kidney disease that is the leading cause of end-stage renal disease (ESRD) or kidney failure. From 1990 to 2006, ESRD due to diabetic nephropathy increased 2.5 times. The medicine has demonstrated the potential to protect kidney function and slow disease pro- gression when added to existing therapy. Early Diabetes Breakthroughs Basic research is important to fi nding new treatments and possibly a cure for diabetes. Recent research discoveries offer hope that they can one day lead to new effective treatments. Some of the new discoveries include: • Researchers at the Harvard Stem Cell Institute discovered a hormone that can stimulate production of insulin-secreting pancreatic beta cells up to 30 times the normal rate in mice. These new cells only produce insulin when the body needs it, potentially leading to a natural regulation of insulin. • Scientists at London’s Imperial College have manipulated a patient’s own stem cells into insulin-secreting cells. Further research aims to inject patients with 100 percent of insulin-producing cells that would release insulin for up to one year. Other scientists at the Walter and Eliza Hall Institute of Medical Research in Australia have isolated stem cells from the pancreas and turned them into insulin- producing cells for the treatment of type 1 diabetes. Key Issues Source: Centers for Disease Control and Prevention (CDC) MILLIONS OF AMERICANS AFFECTED BY DIABETESMILLIONS OF AMERICANS AFFECTED BY DIABETES 19 MILLION AMERICANS have been diagnosed with DIABETES 79 MILLION AMERICAN ADULTS have PREDIABETES 7 MILLION AMERICANS are UNDIAGNOSED EACH DAY MORE THAN 5,000 AMERICAN ADULTS are diagnosed with DIABETES }26 MILLIONAMERICANS DIABETES AFFECTS NEARLY ABOUT ONE-QUARTER ARE UNAWARE THEY HAVE THE DISEASE Source: Centers for Disease Control and Prevention (CDC), National Health and Nutrition Examination Survey (NHANES) TREATMENT IS IMPORTANT TO CONTROL DIABETESTREATMENT IS IMPORTANT TO CONTROL DIABETES 26 MILLION AMERICANS are affected by DIABETES 19 MILLION are DIAGNOSED 7 MILLION are UNDIAGNOSED 16 MILLION are TREATED 3 MILLION are DIAGNOSED but NOT TREATED 8 MILLION controlled DIABETES WITH TREATMENT 8 MILLION have not successfully controlled DIABETES WITH TREATMENT 18 MILLION have UNCONTROLLED DIABETES 8 MILLION have CONTROLLED DIABETES Medicines in Development Diabetes 20144 • A type 1 diabetes vaccine created by researchers at Stanford University shuts down certain segments of the human immune system. Most vaccines aim to boost the immune system to fi ght a virus, but the Stanford vaccine turns off portions of the immune system that are mal- functioning. Type 1 diabetes is an autoimmune disease where the pancreas produces too little or no insulin. • Researchers at the University of Tokyo have identifi ed a molecule that functions similarly to the hormone adipo- nectin, which is secreted by fat cells and helps to regu- late glucose and insulin effectiveness. But the hormone was destroyed by the digestive system when taken orally. The new molecule can be taken orally and was found to be effective when studied in mice. • Doctors at Boston Children’s Hospital have isolated a pathway in animals that triggers T cells to attack the pan- creas. With more research, the newly discovered pathway could lead to better treatments or even a cure for type 1 diabetes. Diabetes Medications—Improving Adherence Improved adherence to diabetes medications can lead to bet- ter health outcomes and reduced costs. According to recent research, diabetes patients who do not consistently take their medicines as prescribed are 2.5 times more likely to be hospitalized than those who follow their prescribed treatment regimens more than 80 percent of the time. In addition, a recent study in Health Affairs projected that improved adher- ence to diabetes medications could avert more than 1 million emergency room visits and close to 620,000 hospitalizations annually, for a total potential savings of $8.3 billion annually. There are several recent studies showing the cost effectiveness of treating diabetes with medication. Some of those include: • Medicare Part A and B costs associated with poor medication adherence are estimated to be up to $840 per month for benefi ciaries with diabetes. The most expensive benefi ciaries were episodic medication users including discontinuers, delayed initiators, and individuals with long gaps in use, according to a study published in Health Affairs. • Insurance plans that perform low on adherence metrics could save $2.1 billion annually for diabetes patients by improving the adherence of their enrollees to even a moderate level. In fact, adherence at a high level could save $19.3 billion, according to a new study. Key Issues Source: American Diabetes Association, U.S. Renal Data System, Amputee Coalition, Agency for Healthcare Research and Quality DIABETES COMPLICATIONS ARE COSTLYDIABETES COMPLICATIONS ARE COSTLY IN THE UNITED STATES, DIABETES IS THE LEADING CAUSE OF kidney failure, non-traumatic lower limb amputations, and new cases of blindness among adults. The rate of amputation is 10 times higher in people with diabetes. The average cost of a hospital stay AVERAGE $10,000 The average cost of amputation surgery NEARLY $40,000 A single year of hemodialysis for kidney failure patients YEARLY $87,000 IN CONTRAST, A YEAR OF MEDICINES AND SUPPLIES that can help a patient avoid those outcomes $4,110 typically averages Source: American Diabetes Association DIABETES COSTS SOCIETYDIABETES COSTS SOCIETY $245 BILLION TOTAL COST FOR DIABETES IN THE UNITED STATES $69 BILLION INDIRECT MEDICAL COSTS $176 BILLION DIRECT MEDICAL COSTS 41 % INCREASE IN 5 YEARS MEDICAL EXPENDITURES ARE 2.3 TIMES HIGHER IN PEOPLE WITH DIABETES Medicines in Development Diabetes 2014 5 Treatment Intensifi cation and Clinical Inertia in Diabetes Care Diabetes is a complex, chronic illness that requires consistent medical care and treatment to help control blood sugar levels and prevent acute or long-term complications of the disease, such as kidney failure and amputations. Despite the availability of effective treatments and clinical guidelines, many individuals with diabetes do not achieve optimal blood glucose levels. One reason is that patients may not receive appropriate and timely changes to or intensifi ca- tion of their medication regimen. Multiple studies have found that there are signifi cant delays in treatment intensifi cation in people with type 2 diabetes despite poor glycemic control. There are several factors that may contribute to optimal glycemic control and infl uence treatment success. However, understanding appropriate intensifi cation of diabetes treat- ment is critical in achieving clinical goals and value to our overall healthcare system. Key Issues DIABETES AND MINORITIES IN THE UNITED STATES Racial and ethnic minority populations in the United States are disproportionately affected by diabetes. According to the U.S. Department of Health and Human Services Offi ce of Minority Health, as compared to non-Hispanic whites: • African-American adults are twice as likely to be diagnosed with diabetes. • Hispanic adults are 1.7 times more likely to have diabetes. • American Indians and Alaska Natives are twice as likely to be diagnosed with the disease. • Native Hawaiians and Pacifi c Islanders are three times more likely to be diagnosed with diabetes. According to the CDC, of people diagnosed with diabetes, 7.1 percent are non-Hispanic whites, while 8.4 percent are Asian Americans, 12.6 percent are African Americans, 11.3 percent are Hispanic Americans, and 16.1 percent are American Indians/Alaska Natives. Source: Diabetes Care ADHERENCE IS KEY TO IMPROVED HEALTH ADHERENCE IS KEY TO IMPROVED HEALTH DIABETES PATIENTS who DID NOT consistently take medications are than those who followed their prescribed treatment regimens 2.5 TIMES MORE LIKELY TO BE HOSPITALIZED Source: Health Affairs ADHERENCE CREATES SAVINGS ADHERENCE CREATES SAVINGS IMPROVED ADHERENCE TO DIABETES MEDICATIONS COULD RESULT IN: 1,082,000 fewer emergency room visits + 618,000 fewer hospitalizations annually = $8.3 BILLION in potential annual savings Medicines in Development Diabetes 20146 Facts About Diabetes in the United States Prevalence1 • Nearly 26 million Americans—8.3 percent of the population —are affected by diabetes; including 7 million who are unaware they have the disease. • One in 10 adults has diabetes now. If current trends continue, as many as one in three will be facing the disease by 2050 due to an aging population more likely to develop type 2 diabetes, increases in minority groups at high risk for the disease, and longer lifespans among diabetes patients. • Of the nearly 25.6 million adults with diabetes, 13 million are men and 12.6 million are women. • In 2010, 10.9 million people aged 65 years and older had diabetes. • About 215,000 people under the age of 20 had diabetes in 2010. • In 2010, 1.9 million patients were newly diagnosed with diabetes. • As many as 79 million people may have prediabetes. Types of Diabetes2 • Type 1 diabetes accounts for 5 percent of all diagnosed cases of diabetes. This type of diabetes is usually diag- nosed in children and young adults. • Type 2 diabetes accounts for 95 percent of all diagnosed cases of diabetes in adults. • Between 2 percent to 10 percent of pregnant women will develop gestational diabetes during pregnancy. And, women who have had gestational diabetes have a 35 percent to 60 percent chance of developing type diabetes within the next 20 years. Mortality • Diabetes is the seventh leading cause of death in the United States.1 • In 2011, 73,282 Americans died as a result of diabetes.1 • Death rates for heart disease and stroke are as many as four times higher among people with diabetes compared to those without the disease.3 Diabetes-Related Conditions • Diabetes is the leading cause of kidney failure, non-trau- matic lower limb amputations, and new cases of blindness among adults.1 • The rate of amputation is 10 times higher in people with diabetes than those without the disease.2 Economic Impact3 • In 2012, the cost of diagnosed diabetes in the United States was $245 billion—$176 billion for direct medi- cal costs (hospital and emergency care, offi ce visits and medications) and $69 billion in reduced productivity. That represents an increase of 41 percent since 2007. • Average medical expenditures among people with diabetes are 2.3 times higher than among those without diabetes. • A signifi cant portion of the U.S. health care dollar goes to treating people with diabetes. More than $1 in $10 is spent directly on diabetes and associated complications, and $1 in $5 is spent on caring for people with diabetes. Sources: 1. National Diabetes Fact Sheet, 2011, U.S. Centers for Disease Control and Prevention (CDC), www.cdc.gov 2. Diabetes Report Card 2012, CDC, www.cdc.gov 3. E