Orexigen ‘Crying All The Way To The Bank’ After ‘Egregiously Unethical’ Actions Reply

On Tuesday morning the members of the Data Monitoring Committee of Orexigen’s Light study began a planned meeting in a hotel in Chicago. They had no way of knowing that in a few hours their routine duties would be completely interrupted by the news that data from the trial– which they thought was known only to them and a very few other people within the company and the FDA– had been revealed to the world by Orexigen. When the news sank in the meeting broke into a scene of high drama and emotion. “I’ve never seen anything like this in 20 years,” said one participant. At one point, I’ve been told, the DMC members were reading my initial story about the data release on a monitor in the meeting room.

The disclosure of the data unleashed a firestorm of criticism directed at Orexigen but also a dramatic 40% increase in the company’s stock, adding about $400 million to Orexigen’s market capitalization. But some believe that despite the short term gain ultimately there may be important negative consequences for the company and its leaders. Certainly the company hasn’t made any friends this week at the FDA or among the doctors and statisticians who perform clinical trials.

The Tuesday meeting was extraordinarily eventful, but in truth the DMC’s activities throughout the trial had never been a day at the beach.

Click here to read the full post on Forbes.

 

Takeda Disagrees With Orexigen Over Data Disclosure Reply

(Updated)

On Tuesday Orexigen sparked a firestorm by disclosing the interim results of an ongoing clinical trial of its weight loss drug Contrave. Takeda, which markets the drug in the US, has released a statement in which it states that it does not support the release of the interim data.

Here is the Takeda statement:

“Pursuant to the Collaboration Agreement between Takeda and Orexigen, Orexigen has the sole right and responsibility for the drafting, prosecution and issuance of Orexigen patent filings.  Takeda respects the need to vigorously protect intellectual property relating to pharmaceutical products; however, Takeda does not support the issuance of patents that contain and disclose interim data results of an ongoing clinical trial.  Takeda is working with the academic leadership of the Light trial (Data Monitoring Committee, Executive Steering Committee) and the FDA to determine the most appropriate next steps for the LIGHT trial.”

Update:

And here is Orexigen’s mildly updated statement about the events:

Orexigen conducted a large cardiovascular outcomes trial in order to file for approval, with the study planned to continue after approval to serve a postmarketing regulatory requirement for additional risk exclusion. We observed an unexpected result in the interim analysis. We filed patent applications based on the results in order to preserve the potential for additional intellectual property. Prior to approval in September 2014, the FDA informed us it had determined that the Light Study would not serve as the postmarketing requirement for Contrave; an entirely new trial would be required. At that point, the company decided to continue with the patent prosecution. The second cardiovascular outcomes trial is expected to start later this year. We are confident that this trial can be enrolled and conducted successfully and we look forward to the results, which are expected by 2022.

On March 3 2015 the USPTO published an issued patent and supporting documentation, and we believed it was appropriate and necessary to make sure this information was equally available to all investors.
Orexigen proactively discussed the challenges inherent in using interim data from ongoing trials for regulatory approvals, and has been, and continues to be, committed to working with FDA and others to support its regulatory obligations to thoroughly explore Contrave’s therapeutic profile. Just as important, Orexigen is committed to its obligation to patients to fully explore the drug’s profile.
Orexigen is also committed to simultaneously meeting its obligations to other regulatory authorities in the U.S., such as the SEC, and abroad, such as the EMA, which are relevant to, and have authority over, its business. The Company is similarly committed to meeting its fiduciary duties to shareholders.

I will have much more to report about this story soon.

 

 

Orexigen Released Interim Data Without Approval Of Trial Leaders Reply

Earlier today Orexigen Therapeutics disclosed positive results from a clinical trial of Contrave, its weight loss pill (a combination of naltrexone and bupropion) that it markets with Takeda. (You can read a good summary of the findings by Adam Feuerstein on TheStreet.)

The surprising thing about the Orexigen disclosure, which was contained in a Form 8-K filed with the SEC, is that it consisted of data derived from an interim analysis of the company’s ongoing Light trial. Normally, interim results are performed by an independent data monitoring committee and the results are known only to the members of the DMC. Occasionally, when important regulatory issues are at stake, the FDA may also be involved. But the detailed results of the analysis are never made public until the trial is stopped.

In this case neither the DMC nor the trial Executive Committee, headed by the Cleveland Clinic’s Steve Nissen, knew about or approved the release of the data. Here’s a statement Nissen sent me:

Click here to read the full post on Forbes.

 

No, Drinking Coffee Won’t Save Your Life Or Prevent Heart Attacks Reply

Once again the media has swallowed the bait hook, line, and sinker. Following the publication of a  a new study in the journal Heart last night, hundreds of news reports have now appeared extolling the miraculous benefits of coffee. Here’s just one typical headline from the Los Angeles Times: “Another reason to drink coffee: It’s good for your heart, study says.”

But a careful look at the study and previous research on coffee makes clear that this type of reporting is completely unwarranted….

Click here to read the full post on Forbes.

 

 

 

Hospitals, Like Vampires, Want Your Blood Reply

Anyone who has been in the hospital, either as a patient or a healthcare provider, is keenly aware that hospitals perform a lot of tests. It has even been suggested that some of those tests may not be necessary. Now a new study published in the Annals of Thoracic Surgery sheds light on just how excessive some of this testing can be.

Researchers analyzed records from 1,894 patients who had cardiac surgery at the Cleveland Clinic and calculated the frequency and total volume of blood drawn from their subjects. They wrote that they “were astonished by the extent of bloodletting” they discovered.

Click here to read the full post on Forbes.

 

Original illustration by Max Husten

Original illustration by Max Husten

 

 

New York City Ebola Doctor Slams Media And Governors Christie And Cuomo Reply

The response in the US to the Ebola crisis last year brought out the worst in the media and our politicians. By comparison, our response to the recent measles crisis– by no means a model for public health communication– had the sophistication and intelligence of a debate at the Oxford Union.

One of the chief victims of the hysteria was Craig Spencer, a New York City emergency room physician who caught Ebola while volunteering in Africa. When he first developed Ebola symptoms after his return to New York City he went straight to the hospital, where he eventually recovered after a harrowing illness. No one– neither his fiancee nor any of the people he interacted with in the days and hours before developing symptoms– caught Ebola from him. Every public health expert said that his behavior was exemplary.

But, as we all know, he did not receive praise in the media, or by the governors of New York and New Jersey. Instead, along with other healthcare workers who heroically went to Africa to help fight the epidemic, he was denigrated and condemned.

Now, months later, Spencer has presented his perspective on these events in an article in the New England Journal of MedicineWe should pay attention to his words. Here are a few excerpts, but by all means click over to NEJM and read the whole thing.

I understand the fear that gripped the country after I fell ill, because I felt it on a personal level. People fear the unknown, and fear in measured doses can be therapeutic and inform rational responses, but in excess, it fosters poor decision making that can be harmful. After my diagnosis, the media and politicians could have educated the public about Ebola. Instead, they spent hours retracing my steps through New York and debating whether Ebola can be transmitted through a bowling ball. Little attention was devoted to the fact that the science of disease transmission and the experience in previous Ebola outbreaks suggested that it was nearly impossible for me to have transmitted the virus before I had a fever. The media… fabricated stories about my personal life and the threat I posed to public health, abdicating their responsibility for informing public opinion and influencing public policy.

Meanwhile, politicians, caught up in the election season, took advantage of the panic to try to appear presidential instead of supporting a sound, science-based public health response. The governors of New York and New Jersey, followed by others, enacted strict home quarantine rules without sufficiently considering the unintended side effects…. At times of threat to our public health, we need one pragmatic response, not 50 viewpoints that shift with the proximity of the next election….

Instead of being welcomed as respected humanitarians, my US colleges who have returned home from battling Ebola have been treated as pariahs….

When we look back on this epidemic, I hope we’ll recognize that fear caused our initial hesitance to respond– and caused us to respond poorly when we finally did. I know how real the fear of Ebola is, but we need to overcome it. We all lose when we allow irrational fear, fueled in part by prime-time ratings and political expediency, to supersede pragmatic public health preparedness.

 

 

Common Pain Drugs Linked To More Problems After A Heart Attack Reply

The cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and diclofenac has been the subject of considerable uncertainty and controversy. Now a new study published in JAMA raises specific concerns about the safety of these drugs in the highly vulnerable population of people who have had a recent heart attack.

Click here to read the full post on Forbes, including comments from Peter Berger and Sanjay Kaul.

 

Everybody Into The Sauna? 1

Spending more time in the sauna may lead to a longer and healthier life– at least if you live in Finland, according to a new study published in JAMA Internal Medicine.

Finnish researchers analyzed data from the Kuopio Ischemic Heart Disease Risk Factor Study. The new analysis focused on 2,315 middle-aged men who had 1, 2-3, or 4-7 sauna bathing sessions per week. After 20 years of followup the rate of sudden cardiac death, fatal coronary heart disease, fatal cardiovascular disease, and all-cause mortality was significantly reduced in people who used the sauna more often.

Click here to read the full post on Forbes, including comments from Franz Messerli, Harlan Krumholz, and John Ryan…

 

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No, The New Cholesterol Drugs From Sanofi And Amgen Aren’t Going To Cost $150 Billion A Year Reply

In an article on the Health Affairs blog 4 CVS executives speculate that the new cholesterol lowering PCSK9 inhibitors from Amgen and Sanofi might achieve yearly sales of $150 billion or even higher. I think these numbers are a bit silly. But first let’s take a look at their extremely bullish case….

Click here to read the full post on Forbes.

 

Amgen Door Hanger

More Guideline Controversy: The Tricky Business Of Calculating Cardiovascular Risk Reply

Calculating cardiovascular risk has become a central and highly controversial component of cardiovascular guidelines. Now a study in the Annals of Internal Medicine finds that most of the commonly employed tools seriously overestimate the risk of people today.

Click here to read the full post on Forbes.

Very Simple High-Fiber Diet Stands Up To American Heart Association Diet Reply

Diets notoriously fail to help people lose a lot of weight. One problem is that most diets include a broad range of restrictions and guidelines that many people find difficult to follow. Another problem is that negative recommendations may have unintended consequences, such as low-fat recommendations leading to increased consumption of refined carbohydrates. Now a new study published in the Annals of Internal Medicine indicates that a radically simple diet containing only one positive rule — eat more fiber — might be nearly as effective and much easier to swallow than a more traditional complex diet.

Click here to read the full post on Forbes.

 

New US Guidelines Will Lift Limits On Dietary Cholesterol Reply

The influential  Dietary Guidelines Advisory Committee has recommended that limitations on dietary cholesterol be removed from the upcoming 2015 edition of Dietary Guidelines for Americans. Recommendations to reduce dietary cholesterol have been a mainstay of the USDA and other guidelines for many years, starting with guidelines from the American Heart Association in the 1960s.

Click here to read the full post on Forbes.

 

 

Another Study Raises Questions About Blood Pressure Guidelines Reply

Although the general benefits of lowering high blood pressure are widely accepted, there has been intense debate over specific goals for treatment and the threshold at which therapy should be initiated.  A large new meta-analsysis published in JAMA helps shed lights on this important controversy.

UK and Australian researchers analyzed the effect of lowering blood pressure in people with type 2 diabetes using data from more than 100,00 people who participated in 40 trials.

Click here to read the full post on Forbes.

 

No, Too Much Jogging Probably Won’t Kill You 1

One again lazy health journalists have fallen down on the job and performed a disservice to the public. The new outrage: a multitude of media reports about a small study on the effect of jogging on mortality. Here are just a few headlines, published minutes after the study was published in the Journal of the American College of Cardiology:

But a careful reading of the paper shows that this small study provides nowhere near enough evidence to support these headlines.

Click here to read the full post on Forbes.

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Study Tests High Blood Pressure Control During Pregnancy Reply

High blood pressure during pregnancy is increasingly common, largely due to older age and obesity. Although there is widespread agreement that hypertension in these women should be treated when it is high enough to raise the risk of stroke, there is little agreement about whether or how to treat mild hypertension.

In a study reported in the New England Journal of Medicine, investigators from Canada reported on 986 hypertensive pregnant women who had diastolic blood pressure of 90 to 105 mm Hg (or, for women already taking a blood pressure drug, 85 to 105 mm Hg). The women were randomized to less tight blood pressure control (target diastolic blood pressure, 100 mm Hg) or tight blood pressure control (target, 85 mm Hg). Three-quarters of the women had hypertension predating their pregnancy.

Click here to read the full post on Forbes.

 

Sanofi And Regeneron Leapfrog Amgen In New Cholesterol Drug Race Reply

Early on Monday Sanofi and Regeneron leapfrogged their rival Amgen to gain leadership in the race to bring a new class of cholesterol drugs to market. The new development could potentially give Sanofi and Regeneron a month on the market by itself before facing competition from Amgen.

Sanofi and Regeneron announced early on Monday that the FDA had accepted for priority review the Biologics License Application (BLA) for alirocumab, their PCSK9 inhibitor…

Click here to read the full post on Forbes.

 

Salt, Science, And The American Heart Association’s Double Standard Reply

Once again the American Heart Association is sticking by its recommendation that pretty much everyone should consume no more than 1,500 milligrams of sodium each day. This is dramatically lower than the 3,500 mg/d the average American now consumes. In a blog post reprinted on MedPage Today the president of the American Heart Association,  Elliott Antman, assails a study published earlier this week which found no benefits– and even a hint of harm–  for elderly people with low sodium consumption.

But Antman only tells one side of the story.

Click here to read the full post on Forbes.

 

New Device to Lower Resistant High Blood Pressure Shows Early Promise 1

A novel implantable device appears to show early promise in the treatment of resistant hypertension. The “Coupler” device from privatelyheld ROX Medical is about the size of a paper clip and is delivered via a catheter to the upper thigh, where it creates a connection between the vein and the artery, which lowers blood pressure in the arteries by letting some of the blood drain off into the veins.

In a paper published in the Lancet, European investigators report the results of an open-label trial in in which 83 patients with persistent high blood pressure despite taking multiple antihypertensive drugs were randomized to implantation of the Coupler device or current treatment…

Click here to read the full post on Forbes, including comments from Franz Messerli, Sripal Bangalore, and Deepak Bhatt.

 

Intense Exercise Doesn’t Eliminate the Hazard of Intense Sitting Reply

James Brown had it right. There may be no better medical advice these days than to “Get Up Offa That Thing.

A large new analysis published in Annals of Internal Medicine supports earlier observations that the health hazards of sedentary behavior aren’t completely neutralized by exercise.

Researchers in Toronto scoured the literature to find studies that assessed the health effects of sedentary behavior adjusted for physical activity. They found 47 studies, including 13 that assessed all-cause mortality, 14 that assessed cardiovascular disease and diabetes, and 14 that assessed cancer. Sedentary behavior was defined as “waking behaviors characterized by little physical movement and low-energy expenditure,” including sitting and television watching.

Click here to read the full post on Forbes.

 

James Brown screenshot

 

How Much Salt Should Old People Consume? Reply

A new study offers fresh evidence that current salt recommendations should be taken with, well, a grain of salt. Current guidelines now recommend that everyone should have sodium intake levels below 2300 mg per day. For many people at higher risk, including everyone over 50 years of age, sodium intake should be below 1500 mg/d. (The American Heart Association promotes the more rigorous goal of 1500 mg/d for everyone.) But a 2013 report from the Institute of Medicine, along with findings from the PURE study published last year, have raised concerns that the lower target level in particular is neither practical nor beneficial.

The new study, published in JAMA Internal Medicine, looks at the growing and important elderly patient population…

Click here to read the full post on Forbes.

 

 

Success For 40-Year Effort In One Rural County To Curb Cardiovascular Disease Reply

A 40-year program in one poor rural county to combat cardiovascular disease appears to have been successful, resulting in reduced rates of hospitalization and death compared with other counties in the same state over the same time period. The new findings from the study are described in a paper published in the Journal of the American Medical Association.

Click here to read the full post on Forbes.

 

Millions Of Americans Taking Aspirin When They Shouldn’t Reply

More than a third of US adults– more than 50 million people– now take aspirin for the primary and secondary prevention of cardiovascular disease. (Primary prevention is the prevention of a first event; secondary prevention is the prevention of a recurrent event.) Although it was once broadly recommended, because of the increased risk of bleeding complications the use of aspirin for primary prevention of cardiovascular disease is now only indicated in people who have a moderate to high 10-year risk. (Aspirin is still broadly recommended for secondary prevention.) Now a new report  published in the Journal of the American College of Cardiology finds that there are still a significant number of people who are receiving aspirin inappropriately.

Click here to read the full post on Forbes.

 

Healthy Habits Of Young Women Lead To Long-Term Health Benefits 1

It may seem obvious but a new study shows that young women with healthy habits are less likely as they age to get coronary heart disease or go on to develop cardiovascular risk factors like high blood pressure, high cholesterol, or diabetes.

Andrea Chomistek and colleagues analyzed data from more than 88,000 women participating in the Nurses Health Study II and who were between 27 and 44 years of age at the start of the study.

Click here to read the full post on Forbes.

 

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No Advantage For Low Glycemic Index Diet Reply

In recent years the glycemic index (GI), a measure of a carbohydrate’s impact on blood sugar, has assumed a major role in discussions about diets and nutrition. Now a new study suggests that by itself, within the context of an otherwise healthy diet, GI may not be an important factor in improving cardiovascular risk.

In a paper published in JAMA, Frank Sacks and colleagues report the results of a randomized, crossover-controlled 5-week feeding trial comparing 4 different diets in 163 overweight or obese adults. The diets were either low- or high-carb and either low- or high-GI. Importantly, all the diets were based on previously established healthy dietary patterns based on the DASH diet, which is low in saturated and total fat and includes substantial amounts of fruits, vegetables, and low-fat dairy foods.

Click here to read the full post on Forbes.