Posts Tagged ‘Cardiovascular Data for Obesity Drugs’

Weight Loss Drugs Losing Traction with FDA and Docs?

Posted by CorDynamics on June 20th, 2014

Developing weight-loss drugs to help the estimated 35% of Americans struggling with obesity should be an easy gain for the biotech and pharmaceutical industry. As of late, it seems to be a losing proposition—for a variety of reasons.

Weight Loss Drugs Losing Traction with FDA and Docs?

FDA Extra Cautious with Safety and Marketing Regulations

Cardiovascular side effects are at the heart of the FDAs concern. The simple fact is that many biological pathways involved in appetite control are also shared with the cardiovascular system.

A generation ago, doctors were prescribing amphetamine-like stimulants, which were appetite suppressants, but also had very unfavorable cardiovascular side effects. In the 1990s the combination of fenfluramine and phentermine (fen-phen) resulted in appetite suppression as well but caused a pathological change in both cardiac valves and pulmonary arterial function.

This tumultuous history has made worldwide regulators particularly sensitive to cardiovascular safety in this therapeutic area. Case in point and as reported in FierceBiotech last week, Orexigen (OREX) had to wait three long years to take a second shot at an approval for its weight drug NB32, earlier called Contrave. Now the company has to wait another three months for an FDA marketing decision as they talk through a regulatory requirement on tracking cardiovascular outcomes among people taking the therapy.

Prescriptions Thin from Physicians

Doctors have not been prescribing weight-loss medications as often as was expected.  Previous safety concerns combined with marginal reported benefits from patients has made physicians think twice before suggesting the medications.

According to Bloomberg, the average weight loss was only 4 percent to 8 percent above what patients taking placebos demonstrated. While this is medically important, it may not be enough to offset side effects as headaches or upset stomach. Also some insurers are reluctant to cover co-pays for drugs.

It’s an interesting caveat. As drug developers we focus so much on FDA approvals, we have to remember the approval of doctors and patients is important as well.

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Who Regulates Drug Safety and Drug Development Better—the FDA or the EMA?

Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on September 26th, 2012

The answer: It depends on who you ask.

The FDA versus the EMA (European Medicines Agency) is a continual debate. Different analysts have different opinions that seemingly change weekly.


What is true, is that both the FDA and the EMA have:

• the tough job of regulating drug development to ensure the approval safe and effective therapies.
• their own set of policies, procedures and guidelines.
• their own governing bodies, growing bureaucracies and shrinking budgets.
• vigilantly regulated drug safety with a keen eye on cardiovascular safety.

Yet with all this in common, why do the FDA and EMA sometimes come to different conclusions?

Many say it’s because the healthcare environments are different between the US and Europe, as well as their vastly different legal systems.

Case Study #1: FDA Says Ok, EMA Says No Way
The weight loss drug, Qysmia, earned FDA approval in July. BUT, Qysmia’s sponsor expects the EMA to recommend against approval based on numerous concerns, including the effects of one of the drug’s two main ingredients, phentermine, and the link to possible heart valve damage.

Case Study #2: EMA Says Yes, FDA Says Not Yet
An advisory panel recently recommended approval of the new anti-clotting drug Eliquis. BUT, the FDA rejected the drug for the second time this past June, citing the need for more information.

What to do?
Outsource to contract research organizations experienced with the ins and outs of both agencies and their specific guidelines—especially when it comes to cardiovascular issues.

I know the FDA. Fortunately, my colleague, Dr. Franz Hock, knows the EMA. While neither of us is so bold as to claim the ability to predict FDA and EMA decisions, we do typically know what cardiovascular questions they will ask and what information they will need to make their decisions. Once you know that, finding the answers gets a bit easier.

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Preclinical Cardiovascular Safety Issues Signal Yield; Not Stop

Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on July 26th, 2012

Obesity drugs are hot on the FDA radar this summer.

Approval of the Vivus weight loss drug Qsymia marks the second obesity treatment to survive the heat of preclinical cardiovascular safety scrutiny.

The Rollercoaster Ride to Approval
The FDA rejected Vivus’ first attempt at approval in 2010.
• The efficacy of Qsymia, a combination of two older approved drugs, appetite suppressant phentermine and antiseizure drug topiramate, was promising with patients losing more than 10 percent of total body.
• The safety concerns of Qsymia created the free fall. The FDA asked Vivus to go back and further investigate the cardiovascular safety of the compound —namely increased blood pressure and heart rates seen in the patient group. (Questions around the possibility for teratogenicity also needed further investigation.)
Vivus Heads Back to FDA Armed with Cardiovascular Safety Data in 2012.
• After completing a year-long clinical study, Vivus presented the FDA with in-depth cardiovascular data.
• While acknowledging potential cardiovascular effects, the FDA approves the new therapy with the following caveat: “Qsymia can increase heart rate; this drug’s effect on heart rate in patients at high risk for heart attack or stroke is not known. Therefore, the use of Qsymia in patients with recent (within the last six months) or unstable heart disease or stroke is not recommended. Regular monitoring of heart rate is recommended for all patients taking Qsymia, especially when starting Qsymia or increasing the dose.”
Qsymia Gains FDA Approval with Postmarketing Requirements.
• A long-term cardiovascular outcomes trial assessing the effect of Qsymia on the risk for major adverse cardiac events such as heart attack and stroke will be required by the FDA.
• The drug will also carry information on the label about potential for teratogenicity.

While the rollercoaster to approval for this drug was not for the feint of heart, it did prove that while the FDA will exercise caution in the face of cardiovascular risks, the agency will look at the big picture. If the benefits out-weigh the thoroughly investigated risks—the FDA is willing to give the drug a green light.

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FDA Panel Recommends More Cardiovascular Data for Obesity Drugs

Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on April 09th, 2012

A recent FDA advisory panel recommended that essentially all new obesity drugs—even those without early signs of adverse cardiovascular effects—should be required to submit Phase 2 or 3 cardiovascular drug safety data.

The FDA Endocrinologic and Metabolic Drugs Advisory Committee voted in favor of going the extra mile to rule out and minimize the cardiovascular risks potentially associated with obesity drugs.

The directive was passed by a 17 to 6 vote in favor of taking a prudent approach, erring on the side of caution for several reasons:

  • The new FDA recommendations for obesity drugs are essentially the same as those currently required for diabetes drugs. This alignment makes sense as some committee members went so far as to argue that obesity could be considered pre-diabetes.
  • With obesity growing at an alarming rate, and millions of would-be patients, a high cardiovascular risk profile could be “catastrophic.”

Why the change in direction?

As discussed in an earlier blog about cardiovascular issues hitting the heart of the obesity drug development debate:

Of course the downside of this new outcome is that it could make obesity drug development even more difficult. However, when a new drug does make it to market, this time we will know it’s been thoroughly vetted from a cardiovascular standpoint.


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