Inhalable insulin for diabetes wins FDA approval

imagesThe Food and Drug Administration on Friday approved a long-delayed inhalable diabetes medication to help patients control their blood sugar levels during meals.

The FDA cleared MannKind Corp.’s drug Afrezza, a fast-acting form of insulin, for adults with the most common form of diabetes that affects more than 25 million Americans. The approval decision comes more than three years after the agency first asked MannKind to run additional clinical studies on the drug.

Diabetes is a chronic condition in which the body either does not make enough insulin to break down the sugar in foods or uses insulin inefficiently. It can lead to blindness, strokes, heart disease or death. In Type 2 diabetes, the most common form of the disease, the body does not use insulin properly. Type 1 diabetes is usually diagnosed in children and young adults. In those cases, the body does not produce insulin.

Afrezza, an insulin powder, comes in a single-use cartridge and is designed to be inhaled at the start of a meal or within 20 minutes of starting. MannKind has said patients using the drug can achieve peak insulin levels within 12 to 15 minutes. That compares to a wait time of an hour and a half or more after patients inject insulin.

The FDA said in its approval announcement that Afrezza is not a substitute for long-acting insulin and is a new option for controlling insulin levels during meals.

The FDA approved the drug with a boxed warning — the strongest type — indicating that the drug should not be used in patients with chronic lung diseases, such as asthma, due to reports of breathing spasms.

Demand for diabetes treatments are surging globally as the prevalence of obesity explodes. Roughly 347 million people worldwide have the disease, according to the World Health Organization.

New effort to fight diabetes in Sonoma County

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Sonoma County medical providers are taking aggressive steps to deal with the high rate of patients with diabetes admitted to local hospitals, a trend that is said to be driving up hospital costs.

In Sonoma County, patients with diabetes account for almost 26 percent of all local hospital admissions, according to a recent UCLA analysis of 2011 hospital patient discharge data. That’s a total of 7,459 hospital admissions.

The added cost of hospital care is estimated at $16.4 million, according to the study, which was conducted by the UCLA Center for Health Policy Research with support from the California Center for Public Health Advocacy.

“We are very concerned about the epidemic of diabetes and the toll that it takes on individuals and the system that cares for them,” said Karen Holbrook, the county’s deputy public health officer.

Holbrook said diabetic patients who are admitted to local hospitals pose more medical complications than those who are not diabetic and often require more tests and treatments. Severe diabetes often results in serious medical conditions such as liver disease and kidney failure, she said.

According to the UCLA study, 31 percent of the state’s hospitalized patients 35 years or older, the age group that accounts for most hospitalizations, had diabetes. The study estimated that the added cost to hospitals in California was $1.6 billion. Hospital stays for diabetic patients in the state cost an average of $2,200 more than for non-diabetic patients, according to the study.

The study’s authors pointed out that 75 percent of this care is covered by Medicare and Medi-Cal, the state’s Medicaid program. Medi-Cal alone pays $254 million in added costs for diabetic patients.

The Tour de Cure event hosted by the American Diabetes Association of Northeast Ohio has already raised $250,000 for diabetes research

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CUYAHOGA FALLS — The Tour de Cure event hosted by the American Diabetes Association of Northeast Ohio has already raised $250,000 for diabetes research in the region, according to Melissa Sutton, the event manager.

The annual event leads riders through a bike route as long as 100 miles. However, riders could also bike shorter distances.

The Saturday ride kicked off at the Cuyahoga Valley Christian Academy on Wyoga Lake Rd. in Cuyahoga Falls.

Participants could also enjoy on-site activities geared towards fun and information about diabetes.

Sutton, who has lived with type one diabetes since she was 9-years-old, says she hopes the ride will combat the stigma the disease faces. “My pancreas stopped working and there’s not a darn thing I can do about it,” Sutton tells Channel 3’s Hilary Golston. “It stops working. So I take it particularly personally when people think it’s a lifestyle disease.”

According to the ADA, 330,000 people have diabetes in Northeast Ohio. “Red riders” or those living with the disease donned red shirts to denote they have diabetes and are participating in the race.

Riders were asked to raise at least $200 to participate, but some raised much more. 11-year-old Gabe Grizwald was able to rake in $2,000. He’s also living with type one diabetes. “I ride for diabetes because it’s just a horrible disease to have and it’s really just changed my life and I think it helps so much when people ride for us and raise money and it really could lead to a cure,” Grizwald tells Golston.

Brian Travalik is Tour de Cure’s red rider ambassador. Decked out in a tutu for flare, he not only lives with diabetes, but represents the so-called “red riders.” Red riders are those who have diabetes and are also participating in Tour de Cure. “It’s a chance to be honored as a hero,” Travalik said. “To see other people with diabetes, it’s a good feeling to be around that comradery of other people that are dealing with that same disease.”

It’s not too late to donate to the cause. You can head over to http://main.diabetes.org/site/TR?fr_id=9375&pg=pfind to give.

 

Human gut cells turned into insulin producers may treat diabetes

Scientists have converted human gut cells into insulin producers by turning off a single gene in an experiment that suggests a novel way forward in treating diabetes.

Using a miniature model of the human intestine, only a few millimeters in size and made from stem cells, the scientists deactivated a gene in the cells tied to metabolic regulation called FOXO1. Once disabled, the cells began producing insulin.

The method, described Monday in the journal Nature Communications, raises the possibility of replacing insulin- making pancreatic beta cells lost in diabetics by using a drug to retrain patients’ existing cells. While progress has been made in generating beta cells from stem cells, the method hasn’t yet produced ones with all the needed functions, said Domenico Accili, the study’s lead author. Plus, such cells would require transplantation.

“We provided a proof of principle that we can do this in human tissues and are also very excited that there is a single identifiable target to trigger this process,” Accili, professor of medicine at Columbia University’s Naomi Berrie Diabetes Research Center in New York, said in an interview. “This is what the pharmaceutical industry is interested in — make a chemical and do what we did in test tubes to administer to persons with diabetes and teach their gut cells to become beta cells.”

The results build on research two years ago by Accili and his team that first tested the approach in mice, successfully converting gut cells into insulin-making cells. In the human cell experiment, the gut cells started releasing insulin after seven days and only in response to insulin.

Now that Accili and his team have shown it works in human cells, their next step is to develop a drug to test in people. Accili said it’s possible that there could be a compound for clinical trials in a year or two.

Diabetes, which results when the body doesn’t use insulin properly or doesn’t make the hormone, is the seventh-leading cause of death in the U.S. Insulin is a hormone secreted by the pancreas that helps the body control blood sugar.

Destruction of insulin-making beta cells in the pancreas is the central feature of Type 1 and Type 2 diabetes. In Type 1 diabetics, the pancreas are destroyed by the immune system and don’t produce insulin. In Type 2, in which the body doesn’t use insulin properly, beta cells become progressively dysfunctional.

One advantage to this experimental approach is that the gastrointestinal tract is partly protected from attack by the immune system, making gut cells less susceptible to destruction, Accili said.

A treatment for diabetes that doesn’t require daily insulin injections would change the treatment landscape for the 29 million diabetics in the U.S. However, it’s likely that any potential drug would first be evaluated for Type 2 diabetes, because of concerns of testing in Type 1 diabetics going without insulin injections, he said.

“The work is a laser-like focus on turning this into a treatment,” Accili said. “We follow 3,000 patients with Type 1 at the Berrie Center alone. That’s our main goal.”

Collaborations with drugmakers are already under way, Accili said, though he declined to name companies.

British drugmaker AstraZeneca Plc helped fund the research, with the National Institutes of Health, the Manpei Suzuki Diabetes Foundation, the Swedish Society for Medical Research, the Japan Society for the Promotion of Science, the JPB Foundation and the Brehm Coalition.

An Uproar Over a Diabetes Article, With a Back Story

Many Times readers, some of whom have Type 1 diabetes, are upset over an article last Sunday in which Elisabeth Rosenthal explored the often extraordinary expense of treating the disease. It was an installment in her series, “Paying Till It Hurts,” about the high cost of medical care in America.

In emails, on blogs and on Twitter, the readers have harshly criticized what they see as the way the article trivializes the treatments and devices that are crucial to their lives or those of their family members. In response to the article’s mention of “high-priced gadgets and disposable accoutrements,” they are using a Twitter hashtag: #notjustagadget.

Over the past few days, I have read much of the criticism, including that on two blogs: Diabetes Mine and A Sweet Life, both of which make points worth considering. I have reread the article itself, many of the reader comments on it, and spoken to the article’s author and to its main editor, Rebecca Corbett.

I’ve also become aware of the key role that several industry-backed patient-advocacy groups have played in heating up the protests.

These are my observations:

1. The article’s headline — “Even Small Medical Advances Can Mean Big Jumps in Bills” — and a few of its language choices could have been better. The headline’s reference to “small advances” immediately set some on edge, its editor and writer strongly believe. (Ms. Rosenthal told me that she found it “tone deaf” and was afraid that it would mislead readers about the article’s overall point.) Before the article went online, and afterwards, Ms. Rosenthal and Ms. Corbett asked for a headline change, but it was tweaked only slightly. And, within the article, the descriptions of some devices, while accurate, might have been written with more awareness of how they would be received.

2. Over all, the article is not guilty of the crimes it’s being accused of – that is, nowhere does the author make light of the disease or the importance of good and innovative treatment. It is well sourced, and based on conversations with both medical experts and those who have the disease. The focus on cost is no surprise; the series, after all, is about the high cost of medical care. “This was not supposed to be about how hard the life of a Type 1 diabetic is – and it definitely is – but rather about the cost issues,” Ms. Rosenthal told me.

What’s more, the article came about because of reader concern over this very subject, Ms. Corbett told me. More than 200 Times readers identified diabetes care as something they hoped Ms. Rosenthal would look at. And the article states, as early as the second paragraph, that devices such as insulin pumps have changed lives for the better: “Such devices, which tailor insulin dosing more precisely to the body’s needs, have transformed the lives of people with Type I diabetes like Ms. Hayley.”

3. JDRF, formerly known as the Juvenile Diabetes Research Foundation, which gets significant funding from industry players and which provides grants for research and lobbies in Washington, sent an email Monday afternoon to Type I patients across the country. It described the organization’s outrage at the article for having made light of advances in diabetes care and it encouraged patients to comment. Other advocacy groups acted similarly.

And it was effective. The initial response to the article was overwhelmingly positive – both in the comments and in email to Ms. Rosenthal. Reaction became much more negative and accusatory after the advocacy groups emailed their members urging them to write to The Times, to light up Twitter and to otherwise respond negatively to the article, Ms. Corbett said. Research by my office backs this up; the tide turned from positive to negative in the comments on Monday afternoon.

I’ve seen this happen before. Once contacted by an advocacy group, people who haven’t already formed an opinion about an article are very likely to read it through a particular lens — if they read it at all before reacting.

4. Articles that delve into medical and other scientific topics are always hard to get right, as they attempt to take esoteric information and translate it for the lay reader. Ms. Corbett told me that, prior to publication, she asked a Times reporter who has Type 1 diabetes — as does the reporter’s mother — to read it for tone and accuracy. In addition, Ms. Rosenthal herself is a medical doctor.

The Times’s correction desk has made one factual correction to the article and another to an accompanying graphic; those corrections have been made online and will appear in print on Sunday.

Even some of the harshest critics of the article say they were gratified to see Type 1 diabetes – and the high cost of living with the disease – get front-page attention in The Times.

Was the treatment of the story perfect in every way? No. Was it essentially sound journalism with an important purpose? I think it clearly was.

Merck, Bristol Diabetes Drugs Linked to Pancreatitis Risk

Diabetes drugs sold by Merck & Co. (MRK) and Bristol-Myers Squibb Co. (BMY) may double a user’s risk of developing an inflammation of the pancreas linked to cancer and kidney failure, an analysis of insurance records shows.

Patients hospitalized with pancreatitis were twice as likely to be taking Januvia, Merck’s top-selling drug, or using Bristol-Myers’s Byetta, than a control group of diabetics who didn’t have pancreatitis, according to the analysis today in the journal JAMA Internal Medicine. Both drugs increase GLP-1, a hormone that stimulates insulin production from the pancreas.

Doctors have been concerned that this category of diabetes treatments may damage the pancreas since the U.S. Food and Drug Administration said in 2007 it received a high number of reports of pancreatitis in patients taking Byetta. The agency issued a similar alert for Januvia in 2009. The study, which analyzed data from 2005 to 2008, showed a doubling in pancreatitis cases.

“This is the first real study to give an estimate of what the risk is, until now we just had a few case reports,” said Sonal Singh, the study’s author and an assistant professor of medicine at Johns Hopkins University in Baltimore. “These drugs are effective in lower glucose, but we should also consider the risk of pancreatitis and balance the risk versus the benefit.”

Merck, the second-largest U.S. drugmaker, reported $4 billion in sales, or about 9 percent of total revenue, from Januvia last year. The daily pill blocks an enzyme that breaks down GLP-1. Janumet, which combines Januvia with the older diabetes drug metformin, generated $1.7 billion in sales last year for Whitehouse Station, New Jersey-based Merck.

Novo’s Victoza

Bristol-Myers, based in New York, acquired Byetta when it bought Amylin Pharmaceuticals last year for about $5 billion. Byetta, which mimics GLP-1, had sales of $148 million for Bristol-Myers last year, and $159 million for Indianapolis-based Eli Lilly & Co. (LLY), which ended its marketing partnership with Amylin in 2011.

“Bristol-Myers Squibb and AstraZeneca are confident in the positive benefit-risk profile of Byetta and Bydureon as demonstrated by extensive clinical trial data and safety surveillance data,” Ken Dominski, a Bristol-Myers spokesman, said in an e-mail. The companies “will continue to carefully monitor any post-marketing reports of acute pancreatitis.”

AstraZeneca Plc (AZN), based in London, has a partnership with Bristol-Myers on diabetes treatments. Bydureon is a longer acting version of Byetta.

Other drugs that increase the level of GLP-1 in the body include Bristol-Myers’s Onglyza and Novo Nordisk A/S (NOVOB)’s Victoza. The analysis only looked at Januvia and Byetta because the other treatments weren’t on the market during the study period. Januvia was approved in the U.S. in 2006, and Byetta in 2005.

Pancreatic Cancer

Singh said long-term studies should be done to determine if GLP-1 therapies also increase the risk of pancreatic cancer.

“We really need to know more about these drugs as pancreatitis is on the pathway to pancreatic cancer,” he said.

Merck said it has thoroughly reviewed preclinical, clinical and post-marketing safety data and found “no compelling evidence of a causal relationship between” the active ingredient in Januvia and pancreatitis or pancreatic cancer.

“Nothing is more important to Merck than the safety of our medicines and vaccines and the patients who use them,” Pam Eisele, a company spokeswoman, said in a statement.

Diabetes Patients

In diabetics, pancreatitis occurs in about 3 in 1,000 patients. A doubling of that risk, such as that seen in the study, would drive that number to 6 in 1,000 for patients taking Byetta or Januvia, Singh said. About 8.6 percent of Americans, or 25 million people, had diabetes in 2010, according to data compiled by Bloomberg. The number may rise to more than 34 million by 2020.

The study looked at 1,268 diabetics who had been hospitalized with pancreatitis and compared them to the same number of patients who didn’t have the condition. Among those with pancreatitis, 87 had filled a prescription for Byetta or Januvia compared with 58 in the control group. When adjusting for variables that can make a patient more likely to develop pancreatitis, the researchers determined there was a doubling of risk, Singh said.

The study was funded by grants from Johns Hopkins, the National Center for Research Resources, and the National Institutes of Health Roadmap for Medical Research.

To contact the reporter on this story: Shannon Pettypiece in New York at spettypiece@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

Caution: New Study Alleging HFCS-Diabetes Link is Flawed and Misleading, Says Corn Refiners Association

WASHINGTON, Nov. 26, 2012 — Authors Target HFCS, while Ignoring it is Nutritionally Equivalent to Sugar

WASHINGTON, Nov. 26, 2012 /PRNewswire-USNewswire/ — A new study, to be released Tuesday, November 27, by researchers from USC and Oxford, uses a severely flawed statistical methodology and ignores well established medical facts to “suggest” a unique link between high fructose corn syrup (HFCS) and Type 2 diabetes. A previous study critical of HFCS from the lead author, Dr. Michael I. Goran, has met with severe criticism for both its study design and conclusions.  Most importantly, Dr. Goran’s newest attack on HFCS fails to account for widespread agreement among scientists and medical doctors that HFCS and sucrose (table sugar) are nutritionally equivalent.

Statement attributed to Audrae Erickson, President, Corn Refiners Association

“This latest article by Dr. Goran is severely flawed, misleading and risks setting off unfounded alarm about a safe and proven food and beverage ingredient.  There is broad scientific consensus that table sugar and high fructose corn syrup are nutritionally and metabolically equivalent.  It is, therefore, highly dubious of Dr. Goran–without any human studies demonstrating a meaningful nutritional difference between high fructose corn syrup and sugar–to point an accusatory finger at one and not the other.  Dr. Goran commits the most fundamental of research errors:  Just because an ingredient is available in a nation’s diet does not mean it is uniquely the cause of a disease.

“If this study shows anything, it is that there is an association between body mass index (BMI) and diabetes prevalence.  Take for example, Japan, where the average BMI is 22.59, and Mexico, where the average BMI is 27.59.  Even though Japan consumes more HFCS every year than Mexico, the prevalence rates of diabetes in Japan are about half of Mexico.  This example alone shows that Dr. Goran’s hypothesis is totally flawed.

“This is not the first time HFCS detractors have tried to use statistical analysis to ‘suggest’ a unique causal link between HFCS and obesity.  The co-authors of the infamous 2004 Bray and Popkin paper, which Dr. Goran relies on, now admit they reached an erroneous hypothesis.  As one author of the 2004 paper confirmed, ‘All sugar you eat is the same, that’s what we know now that we didn’t know in 2004.’

“Rigorous, credible scientific inquiry into the health effects of sweeteners is essential to advancing our understanding of a healthy diet.  But Dr. Goran’s latest quest to condemn high fructose corn syrup crosses the line from science to advocacy.

“The bottom line is this is a poorly conducted analysis, based on a well-known statistical fallacy, by a known detractor of HFCS whose previous attack on the ingredient was deeply flawed and roundly criticized.  The common sense message for consumers to understand is to watch their intake of all extra calories, including all added sugars.”

Statement attributed to James M. Rippe, M.D., Professor, BioMedical Sciences, University of Central Florida (and consultant to CRA)

“Diabetes is a complex disease with many underlying factors.  It is highly unlikely that one component of the diet is uniquely related to diabetes. There are well-established links between obesity and diabetes. That is where we should be focusing our attention rather than vilifying one component of the diet.”

Five Major Reasons the Goran Study is Flawed and Unreliable

1. HFCS and sugar are nutritionally equivalent.  There is broad scientific consensus that HFCS and table sugar are nutritionally and metabolically equivalent, and the American Medical Association has concluded that HFCS is not a unique cause of obesity.  There is absolutely no scientific or medical basis for Dr. Goran to distinguish HFCS from table sugar in terms of human health effects.

2.  Glucose is wrongly compared to fructose.  The studies that are cited by Dr. Goran to justify his belief that fructose is dangerous are largely studies that compare pure fructose to pure glucose, neither of which is consumed in isolation in a normal diet.  HFCS and table sugar contain about equal amounts of glucose and fructose–not fructose or glucose, alone. When the same measurements cited by Dr. Goran are made comparing HFCS to sucrose, all of the differences disappear. Stating that fructose and glucose are treated differently in the liver is misleading and irrelevant. Humans almost always consume these two simple sugars together, not in isolation, and both HFCS and table sugar contain approximately equal amounts of both.

3.  Dr. Goran’s study is based on an “ecological fallacy”.  It associates a characteristic of a large group (diabetes) to a single factor (high fructose corn syrup availability), with no clear evidence of causation.  Comparing levels of HFCS “availability” to a disease with multiple contributing factors (diabetes) is an extremely weak association, particularly given the study’s grandiose claim of a global significance.  In fact, Dr. Goran and his co-authors are forced to admit in their own paper that the arguments they make “could be subject to ecological fallacy” and that the approach they have taken “might introduce errors.”

4.  Goran’s previous HFCS study was shown to be deeply flawed.  For a prior study purporting to find higher than expected fructose in HFCS sweetened drinks, Dr. Goran used the wrong laboratory test methodology.  This flawed approach falsely inflated the levels of fructose and glucose in HFCS and in HFCS-sweetened products.  Dr. Goran later admitted that he and his team “are not disputing the sugar composition of HFCS” and that there were errors caused by the limitations of the method used in the study.  Dr. Goran’s previous study has been roundly criticized.

5.  Isolating one aspect of a national diet and implying that it is a singular cause of diabetes is unwise, unscientific and highly speculative. Diabetes is a complicated condition just like obesity.  The scientific community would not support this kind of approach, linking the availability of one component of the diet to increased risk of diabetes.   For example, drawing from the study’s own data, Japan consumes more high fructose corn syrup every year than does Mexico. Yet the rates of diabetes in Japan are about half of what you see in Mexico.  There are also epidemics of obesity and diabetes in many countries where no high fructose corn syrup is even being used.  Thus, to make a comparison between high and low “availability” of HFCS and diabetes in certain countries is simply misleading.  And Dr. Goran fails to put HFCS and sucrose consumption into proper global perspective: sucrose comprises more than 90% of annual sweetener consumption worldwide.

CONTACT: David Knowles (202) 331-1634

The Corn Refiners Association (CRA) is the national trade association representing the corn refining (wet milling) industry of the United States. CRA and its predecessors have served this important segment of American agribusiness since 1913. Corn refiners manufacture sweeteners, ethanol, starch, bioproducts, corn oil and feed products from corn components such as starch, oil, protein and fiber.

Visit us on the Web at www.Corn.org

SOURCE Corn Refiners Association

Read more here: http://www.sacbee.com/2012/11/26/5010805/caution-new-study-alleging-hfcs.html#storylink=cpy

FDA Approves Lucentis® (Ranibizumab Injection) for Treatment of Diabetic Macular Edema (DME)

– First Major Treatment Advance in More Than 25 Years for Sight-Threatening Condition –
South San Francisco, Calif. — August 10, 2012 — Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that Lucentis® (ranibizumab injection) was approved by the U.S. Food & Drug Administration (FDA) for treatment of diabetic macular edema (DME), an eye condition in people with diabetes that causes blurred vision, severe vision loss and sometimes blindness. Diabetes is now the leading cause of new cases of blindness in American adults1 and DME is estimated to affect more than 560,000 Americans with the disease.2
Lucentis is the first and only FDA-approved medicine for DME, a condition for which the standard of care has not changed significantly in more than 25 years. To date, the standard of care in the U.S. for DME has been laser surgery, which slows the rate of vision loss and helps stabilize vision, but has demonstrated only limited ability to restore lost vision.3
“For the first time, Americans with diabetic macular edema will have access to an FDA-approved medicine shown to help many patients rapidly regain substantial amounts of lost vision,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “We developed Lucentis to treat diseases of the eye and are pleased to have received this third U.S. indication to help a new population of people whose eyesight may be affected by diabetes.”
“This approval is an important advancement in the fight against blindness for people with diabetes,” said David M. Brown M.D., Retinal Specialist at The Methodist Hospital, Houston Texas, and clinical trial investigator. “Now that it will be available, Lucentis therapy can begin to make a difference in the lives of our patients with DME.”
Lucentis 0.5 mg once monthly was first approved by the FDA for treatment of wet age-related macular degeneration (AMD) in 2006 and for macular edema following retinal vein occlusion (RVO) in 2010. Lucentis 0.3 mg once monthly was approved for DME, and physicians can order immediately with shipments expected to begin August 15.
Lucentis Efficacy in DME
The approval of Lucentis in DME was based on Genentech¿s Phase III trials, RIDE and RISE, two identically-designed, parallel, double-masked, three-year clinical trials, which were sham-treatment controlled for 24 months. A total of 759 patients were randomized into three groups to receive monthly treatment with 0.3 mg Lucentis (n=250), 0.5 mg Lucentis (n=252) or sham injection (control group, n=257). Primary outcomes were evaluated at 24 months and have been published in Ophthalmology.4
In the studies, treatment with Lucentis demonstrated improved clinical outcomes including substantial visual gain for many DME patients. Results showed patients who received 0.3 mg Lucentis experienced significant, early (Day 7) and sustained (24 months) improvements in vision:

 

  • More patients who received Lucentis were able to read at least three additional lines (15 letters) on the eye chart at 24 months: RIDE: 34 percent in the 0.3 mg group versus 12 percent in the control group; RISE: 45 percent, 0.3 mg versus 18 percent, control (primary endpoint)
  • Patients who received Lucentis had average vision gains exceeding two lines (10 letters) on the eye chart at 24 months: RIDE: 10.9 letters, 0.3 mg versus 2.3 letters, control; RISE: 12.5 letters, 0.3 mg versus 2.6 letters, control
  • Significant gains in average vision were observed 7 days after the first treatment
  • Patients who received Lucentis were significantly more likely to maintain their vision (lose < 15 letters on the eye chart) at 24 months: RIDE: 98 percent, 0.3 mg versus 92 percent, control; RISE: 98 percent, 0.3 mg versus 90 percent, control

For all time points comparing 0.3 mg Lucentis to control through Month 24 p < 0.01.
Vision improvements observed in patients treated with Lucentis at 24 months were maintained with continued treatment through 36 months.
Lucentis Safety in DME
The benefit/risk profile of Lucentis was favorable in patients with DME through 36 months in the clinical trials. Pooled safety analysis of RIDE and RISE at 24 months showed:

  • The ocular safety of Lucentis in patients with DME was generally consistent with that established in patients with wet AMD and RVO (through 36 months).
  • The most common ocular events occurring at a higher rate in patients receiving 0.3 mg Lucentis compared to the control groups included conjunctival hemorrhage (bleeding under the lining of the eye): 47 percent, 0.3 mg versus 32 percent, control; eye pain: 17 percent, 0.3 mg versus 13 percent, control; foreign body sensation in eyes: 10 percent, 0.3 mg versus 5 percent, control; vitreous floaters: 10 percent, 0.3 mg versus 4 percent, control; and increased eye pressure: 18 percent, 0.3 mg versus 7 percent, control.

Although uncommon, trends toward increased rates of arteriothromboembolic events (ATEs) such as vascular death, deaths of unknown cause, nonfatal heart attacks and nonfatal strokes, have been observed in prior studies of Lucentis in other diseases.

  • Rates of these events were similar among DME patients receiving 0.3 mg Lucentis and the control groups at 24 months at 5.6 percent, 0.3 mg versus 5.2 percent, control. The rate of ATE events at 36 months was 10.8 percent for patients in the 0.3 mg treatment group (control period ended at 24 months).
  • The rate of stroke in DME patients at 24 months was 1.2 percent, 0.3 mg versus 1.6 percent, control. The rate of stroke at 36 months was 2.0 percent for patients in the 0.3 mg treatment group.

Pooled analyses also showed the rate of fatal events (death from any cause) in patients treated in the DME trials was low, and many causes of death were not unusual for patients with advanced diabetes complications. However, a potential relationship between the events and intravitreal use of VEGF inhibitors cannot be excluded. The rate of fatalities at 24 months was 2.8 percent, 0.3 mg versus 1.2 percent, control. The rate of fatalities at 36 months was 4.4 percent for patients in the 0.3 mg treatment group.
About DME
DME is swelling of the macula, the central part of the retina responsible for sharp, central vision.5 DME begins with diabetes, which can cause damage to blood vessels in the eye over time. When this happens, a patient is said to have diabetic retinopathy, the most common diabetic eye disease. The damaged blood vessels can leak blood and fluid, causing swelling and blurred vision, severe vision loss and sometimes blindness.5
Nearly 26 million Americans have diabetes, which has become the leading cause of new cases of blindness in adults aged 20-74.1 Among Americans aged 40 years and older, more than 4.2 million have diabetic retinopathy, according to the 20052008 National Health and Nutrition Examination Survey (NHANES).6 A subsequent analysis estimates that 560,500 have DME.2 It has also been estimated that up to 10 percent of people with diabetes will get DME during their lifetime.7
About Lucentis
Lucentis is a prescription medicine for the treatment of patients with wet AMD, macular edema following RVO and DME.
Lucentis is a recombinant humanized monoclonal antibody fragment (lacking an Fc region). Lucentis is the first VEGF inhibitor specifically designed for use in the eye to bind to and inhibit VEGF-A, a protein that is believed to play a critical role in the formation of new blood vessels (angiogenesis) and the hyperpermeability (leakiness) of the vessels.
In wet AMD, these new blood vessels grow under the retina and leak blood and fluid, causing rapid damage to the macula. Lucentis administered monthly in wet AMD clinical trials demonstrated an improvement in vision of three lines or more on the study eye chart in up to 41 percent of patients at two years. Nearly all patients (90 percent) treated monthly with Lucentis in those trials maintained (defined as losing < 15 letters) vision.
In RVO, angiogenesis and hyperpermeability can lead to macular edema, the swelling and thickening of the macula. Lucentis administered at 0.5 mg monthly in RVO clinical trials demonstrated the following average vision gains for patients at six months: patients with branch-RVO experienced an average gain of 18.3 letters on the study eye chart (compared to 7.3 letters for the control group) and patients with central-RVO experienced an average gain of 14.9 letters on the study eye chart (compared to 0.8 letters for the control group).
Lucentis has been rigorously studied in multiple retinal diseases in 27 clinical trials involving more than 10,500 patients worldwide.
Outside the U.S., Lucentis has received regulatory approval for treatment of visual impairment due to DME in more than 75 countries, for treatment of wet AMD in more than 100 countries and for treatment of RVO in more than 70 countries.
Lucentis was discovered by Genentech and is being developed by Genentech and Novartis for diseases or disorders of the eye. Genentech retains commercial rights in the U.S. and Novartis has exclusive commercial rights for the rest of the world.
Lucentis in DME Indication Statement
Lucentis 0.3 mg (0.05 mL of 6 mg/mL Lucentis solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days) for treatment of diabetic macular edema (DME).
Lucentis Safety
Lucentis is a prescription medicine given by injection into the eye, and it has side effects. Lucentis is not for everyone. You should not use Lucentis if you have an infection in or around the eye or are allergic to Lucentis or any of its ingredients.
Some Lucentis patients have serious side effects related to the injection. These include serious infections inside the eye, detached retinas, and cataracts. Other uncommon serious side effects include inflammation inside the eye and increased eye pressure. These side effects can make your vision worse. Some patients have had increased eye pressure within one hour of an injection. Your eye doctor should check your eye pressure and eye health during the week after your Lucentis injection.
Uncommonly, Lucentis patients have had serious, sometimes fatal, problems related to blood clots, such as heart attacks or strokes.
If your eye becomes red, sensitive to light, or painful, or if you have a change in vision, call or visit your eye doctor right away.
The most common eye-related side effects are increased redness in the white of the eye, eye pain, small specks in vision, and increased eye pressure. The most common non-eye-related side effects are nose and throat infections, headache, lung/airway infections, and nausea.
Lucentis is for prescription use only.
For additional safety information, please talk to your doctor and visit http://www.lucentis.com for the Lucentis full prescribing information.
Genentech’s Commitment to Patient Access
At Genentech, we develop medicines for serious or life-threatening medical conditions and we believe they should be accessible for the patients who need them. Genentech Access Solutions is here to help when a Genentech medicine is prescribed. We offer a full range of programs and services to meet the needs of patients and health care professionals. What patients need for access¿from benefits investigations through patient assistance options¿is available through Genentech Access Solutions. For more information, please visit Genentech-Access.com.
About Genentech
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

 

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Antipsychotic drugs tied to diabetes in pregnancy

(Reuters Health) – Women who take antipsychotic medications while pregnant may have an increased risk of developing diabetes, according to a new Swedish study.

Researchers found that out of 360,000 women who gave birth over a four-year span, about four percent of those on antipsychotic drugs developed gestational diabetes. Meanwhile, only 1.7 percent of women who weren’t taking antipsychotics were diagnosed with pregnancy-related diabetes.

“It’s a very important and difficult area to study, because severe mental disorders – such as schizophrenia and bipolar disorder – often require consistent medication even if a woman is pregnant. So it’s very important for us to know all the possible adverse effects from the medications,” said Dr. Robert Bodén, the study’s lead author from Uppsala University in Sweden.

Bodén and his colleagues write in the Archives of General Psychiatry that they expected to see a link between the development of gestational diabetes and olanzapine – sold under the brand name Zyprexa – and clozapine – sold as Fazaclo or Clozaril.

Those two drugs are newer antipsychotics and have been linked to weight gain, high cholesterol and increased insulin resistance, according to the authors. “We thought (gestational diabetes risk) would be more exaggerated for those treated with the two (newer drugs) but we were surprised we saw it for all antipsychotics,” said Bodén.

For their study, the researchers collected information from various databases on all women who gave birth in Sweden from mid-2005 through the end of 2009. Of those, 169 took olanzapine, clozapine or a combination of the two during pregnancy, 338 took other types of antipsychotics and 357,696 were not on any antipsychotic drugs.

Seven of the women on the newer antipsychotics and 15 on the older versions became diabetic during their pregnancies, compared to 5,970 women not on antipsychotics. That, the researchers say, works out to women on the medications being twice as likely to develop gestational diabetes.

The study, however, cannot prove the drugs caused gestational diabetes. It could be that women on antipsychotics have other traits that leave them more vulnerable to diabetes. Poor diet and lack of exercise, for example, have been tied to the condition.

Dr. Peter Manu, who has studied antipsychotics at the Zucker Hillside Hospital in Glen Oaks, New York, told Reuters Health the study also may not have tracked women for long enough to see a difference in diabetes risk between the newer and older medications.

“The message there is that – to some extent – even looking over a period of nine months may not give the entire story,” said Manu, who was not involved with the new research.

NO LINK TO BABY SIZE

The researchers also looked at whether antipsychotic drugs were tied to differences in baby size at birth, because women with gestational diabetes may deliver bigger babies. But there was no clear link.

Bodén told Reuters Health his team did find that babies born to mothers on the newer antipsychotic drugs were more likely to have big heads. He said this is the first time that’s been shown, however, and there needs to be more research into that finding.

As for what women with schizophrenia or bipolar disorder can do to limit their risk of gestational diabetes, Bodén said that varies patient to patient.

“You have to balance a lot of things,” he said.

The approach, he said, depends on what medications women need, how long they’ve been pregnant and which medications are linked to pregnancy-related problems.

 

Bristol’s Amylin Deal Heralds Acquisition Hunger

Bristol-Myers Squibb Co.’s $5.3 billion deal to buy diabetes drugmaker Amylin Pharmaceuticals Inc. (AMLN) gives Bristol (BMY) immediate access to a market of growing medical need, while heralding a burgeoning hunger among pharmaceutical companies for acquisitions.

The agreement is the second announced this year for Bristol, and the largest for the industry. It comes after the blood-thinner Plavix, Bristol’s top seller in 2011 at $7.1 billion, faced generic competition for the first time in May.

Drugmakers last year lost patent protection on products valued at $34 billion in annual sales, an amount that will rise to $147 billion by 2015, according to data compiled by Bloomberg. The Bristol deal would be the fifth sealed in 2012 for more than $1 billion, more than the three in each of the previous two years. More deals like this one are coming, said Seamus Fernandez, of Leerink Swann & Co.

“We are on the cusp of the next consolidation wave,” said Fernandez, a Boston-based industry analyst, by telephone. “There just isn’t enough top-line growth in the industry.”

AstraZeneca, Pfizer

Last year, drugmakers “took a little bit of a pause,” he said. “Now, I think we are going to see a reacceleration in that number.” Fernandez identified London-based AstraZeneca Plc (AZN), New York-based Pfizer Inc. (PFE) and Merck (MRK) & Co., of Whitehouse StationNew Jersey, as possible acquirers during the year ahead.

“AstraZeneca and Pfizer have pretty much been out of the market,” he said. “We should anticipate they will be back. I wouldn’t be surprised with some of the spin outs to see more large acquisitions being considered.”

Bristol said on June 29 that it agreed to buy San Diego- based Amylin for $31 a share in cash, a 10 percent premium to the June 29 closing price. The New York-based drugmaker also announced it will be paid $3.4 billion by AstraZeneca to help develop Amylin’s drug pipeline.

Amylin rose 8.9 percent to $30.71 at the close of New York trading. The stock was at $15.39 on March 27, the day before it was reported Bristol had made an unsolicited offer of $22 a share. Bristol gained less than 1 percent to $36.05.

The AstraZeneca partnership means the companies will share both the risk and the reward of potential treatments.

Going to Fail

“Drugmakers say they would do more deals, but the issue with biotech companies is that most of the drugs they’re developing are going to fail,” said Mark Schoenebaum, an analyst at ISI Group in New York, by telephone. “So the biggest issue isn’t the willingness to do a deal, or the appetite to do deals, but rather finding stuff that’s worth buying.

“When you have good assets coming along you’ll see deals,” Schoenebaum said.

Amylin offered Bristol two products already approved for sale by U.S. regulators — the twice-daily diabetes injection Byetta, which generated $518 million in 2011, and a longer- acting form of that drug, called Bydureon, that’s taken just once a week.

“We believe this is a very strategic transaction for Bristol Myers Squibb,” said Bristol Chief Executive Officer Lamberto Andreotti in a conference call with investors. “It will enhance our already strong diabetes portfolio, something that is very important in light of the significant unmet medical need.”

Creating Value

If the easier-to-use Bydureon becomes a $2 billion product, “it will create value” for shareholders, Schoenebaum said. “We saw a lot of interest in Amylin because it’s diabetes and there aren’t a lot of diabetes assets out there. It is increasingly strategic to be in that market.”

Bristol’s own experimental diabetes product, dapagliflozin, failed to win U.S. marketing approval in January, when the Food and Drug Administration asked for more data to assess its risks and benefits. The treatment, being developed with AstraZeneca, was recommended for approval by advisers to regulators in Europe, and the companies are awaiting a decision.

Diabetes has become a key target for pharmaceutical companies as a result of rising obesity rates and the aging of the Baby Boom generation. About 346 million people globally have the illness, and the number of deaths may double from 2005 to 2030, according to the World Health Organization.

AstraZeneca, Paris-based Sanofi (SAN) and Merck also made offers during a bidding process, people with knowledge of the process had said.

Marketing Partnership

Amylin ended a marketing partnership on Bydureon and Byetta with Indianapolis-based Eli Lilly & Co. (LLY) in November, and had been seeking a partner to sell the medicine outside the U.S. The company began to seek acquisition suitors after rejecting a $22- a-share offer from Bristol in February, people familiar with the matter said earlier this year.

For Bristol, the purchase is the largest of 19 since 2007, when it began its so-called string of pearls acquisition strategy designed to revitalize the company in the face of patent losses and produce a more diverse stable of products.

This year, there have been four announced acquisitions of biotechs for more than $1 billion, and one takeover attempt that’s still active, according to data compiled by Bloomberg.

GlaxoSmithKline Plc’s $2.6 billion hostile offer for Human Genome Sciences Inc. is still pending. The two companies have a partnership on the approved lupus drug Benlysta, as well as experimental medicines for diabetes and cardiovascular disease.

Bristol purchased Inhibitex in January for $2.5 billion to gain access to experimental hepatitis C medicines, while Agilent Technologies Inc. bought Danish cancer-diagnostics maker Dako for $2.2 billion to expand its life-science business.

AstraZeneca took over Ardea Biosciences Inc. for $1.26 billion in April, adding experimental drugs for gout and cancer.

Amylin was advised by Goldman Sachs & Co. and Credit Suisse Securities LLC. Citigroup Inc. and Evercore Partners Inc. (EVR) are serving as financial advisers to Bristol. Bank of America Merrill Lynch advised AstraZeneca.

To contact the reporters on this story: Meg Tirrell in New York at mtirrell@bloomberg.net; Ryan Flinn in San Francisco at rflinn@bloomberg.net; Jeffrey McCracken in New York atjmccracken3@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.netScience