Posts Tagged ‘Cardiovascular Studies’
Posted by CorDynamics on April 03rd, 2013
Invokana (canagliflozin) has been approved by the FDA for patients with Type II diabetes—with two cardiovascular caveats.
- Leading up to approval, FDA reviewers highlighted the increased risk of cardiovascular problems to patients on the therapy as it lowered blood sugar but raised cholesterol in clinical trials.
- A complete cardiovascular outcomes trial must be conducted.
Ivonkana is at the head of the new class of SGLT2 inhibitors.
These inhibitors block a protein associated with the reabsorption of glucose in kidneys to help diabetics clear blood sugars more efficiently.
“Invokana is the first diabetes treatment approved in a new class of drugs known as sodium-glucose co-transporter 2 (SGLT2) inhibitors,” said Mary Parks, M.D., director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “We continue to advance innovation with the approval of new drug classes that provide additional treatment options for chronic conditions that impact public health.”
In a statement regarding the approval of Invokana, the FDA is requesting five postmarketing studies for Invokana: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; a bone safety study; and two pediatric studies under the Pediatric Research Equity Act (PREA), including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study.
Filed under: Drug Safety Services |
Posted by CorDynamics on March 05th, 2013
The FDA rejected Xarelto (rivaroxaban) for a second time in less than a year as a drug therapy for patients with acute coronary syndromes.
Timeline of Concern
May 2012: By a narrow margin, an FDA Cardiovascular and Renal Drugs Advisory Panel recommended against expanding the marketing indications to prescribe Xarelto as an acute coronary syndrome therapy.
June 2012: The FDA confirmed panel opinion and denied expanding Xarelto as an acute coronary syndrome therapy, citing concern over incomplete data.
- The gaps occurred after nearly 1,300 patients dropped out of 15,000+-subject final-phase study and withdrew consent for access to their health information. There were also notable concerns about bleeding risks – in the absence of antidote – for rivaroxaban.
March 2013: FDA rejects Xarelto bid sending a second “complete response letter” which infers even more data is again requested.
• Xarelto (rivaroxaban) is a factor Xa inhibitor—a blood thinner. The drug is already approved for stroke in patients with nonvalvular atrial fibrillation. It’s also indicated for those undergoing joint replacement surgery to prevent deep vein thrombosis.
• Acute coronary syndrome (ACS) is a catch-all phrase referring to conditions involving coronary artery obstruction.
• The studies under review evaluated the safety and efficacy of rivaroxaban in more than 19,000 ACS patients in addition to aspirin with or without thienopyridine therapy.
• If the panel had advised approval it would have meant an endorsement of treating ACS patients with combination therapy (aspirin, thienopyridine and rivaroxaban).
What Does This Mean for Drug Developers?
The earlier potential cardiovascular questions can be answered the better.
Investing in thorough safety and efficacy studies from preclinical all the way through the clinical phases of drug development is key.
Filed under: Atrial Fibrillation, Drug Safety Services, Preclinical Consulting Services |
Posted by CorDynamics on February 28th, 2013
We covered the complexities surrounding heart failure drug development in a blog we published last summer. In it, we pointed out:
Once developers clear the hurdle of finding a compound with promise, the bar is set high for proving their efficacy and superiority over existing drugs to gain regulatory approval.
Most heart failure medicines have to go through a variety of different measures for efficacy. One of which is “quality of life” as measured by the American Heart Association ratings for heart failure.
For example: Can bedridden patients begin to get out of bed and move around more?
Unfortunately for researchers working on spironolactone, recent reports illustrate this case in point.
In patients experiencing heart failure with preserved ejection fraction, spironolactone did in fact demonstrate improved left ventricular diastolic function but did not have any effect on heart failure symptoms, quality of life, depressive symptoms or hospitalizations.
Although the trial did show improvements in diastolic abnormalities of the left ventricle, the lack of clinical improvements means researchers will most likely conduct further studies, perhaps with patients in more advanced stages of heart failure.
We work in the area of heart failure discovery with some clients who are taking a more non-traditional approach to treating this condition. An example of this would be using dual pharmacology involving both increasing heart function while simultaneously reducing the extrinsic burdens.
Filed under: Drug Discovery Services, Heart Failure |
Posted by CorDynamics on January 14th, 2013
When the FDA gave the green light to an orphan drug with approval of Juxtapid (lomitapide) it marked a 16-year high of drug approvals by the US Agency in 2012.
Thirty-nine new chemical entities were approved last year, with many of them being therapies for rare diseases. This underscores our industry’s increased focus on specialized, niche products.
The drug meets the previously unmet needs of patients, usually children. with homozygous familial hypercholesterolemia (HoFH) who are unable to remove LDL cholesterol—often known as the “bad” cholesterol—from the blood.
Lomitapide works as an anti-cholesterol agent by inhibiting the microsomal triglyceride transfer protein. This moiety is necessary for assembly of very low density lipoprotein (VLDL) in the liver. VLDL is converted in the blood stream to LDL. Patients with HoFH are at severe risk for atherosclerosis (hardening of the arteries), which causes heart attacks, strokes and other serious vascular conditions usually before the onset of puberty.
HoFH occurs at a rate of approximately 1:1,000,000 in the general population.
Points to Consider
Filed under: Drug Safety Services, Heart Failure |
- The efficacy of Juxtapid increases in conjunction with diet changes and other cholesterol lowering treatments.
- The FDA is requiring three post-marketing studies, including a long-term registry of HoFH patients taking Juxtapid to determine the long-term safety.
- Due to lingering questions on the safety of Juxtapid, the FDA insisted a ‘black-warning’ be added to the drug’s labeling.
Posted by Theresa Gralinski, Marketing Director at CorDynamics on November 14th, 2012
I spent most of last week at the American College of Toxicology meeting in Orlando taking the industry’s proverbial temperature.
Over the last four years this meeting’s attendees seemed concerned about feverishly downsizing, feverishly cutting budgets or feverishly outsourcing. People just didn’t feel well. This year attendees seemed to be “feeling” healthy and more optimistic.
I saw five clear signs that industry outsourcing is officially IN.
1. Back to Business—With mass waves of downsizing behind a number of our colleagues, clients and competitors, the focus of discussions turned to current programs and upcoming projects.
2. Changing Roles—Longtime friends were embracing new positions, translating their pharma drug safety and drug discovery experience into success at virtual biotechs or contract research organizations.
3. New CROs and Consultants Join the Ranks—We welcomed new CROs to the “club” and I met with quite a few toxicologists who have decided to work as consultants to share their expertise to meet the anticipated demand.
4. Buzzwords—Collaboration. Customized. Experience. Responsive. Did I say collaboration?
5. Social Media…Really?—Admittedly the industry is still skeptical of the idea in a regulated industry. However with more drug developers looking for external services, vendors and CROs want to be easily found. (Shameless examples: cardiovascular CRO, prolonged QT interval, cardiovascular pharmacology.) Social media is a good way to get the message out.
I polled attendees on their comfort levels with the top social media platforms. Results: LinkedIn=Great; Blogging=Good; Twitter=So-So; Facebook=No Thanks.
Did you get a different temperature reading from the meeting? Or, did you sense a healthier optimism as well? Feel free to comment here or you can find me on Linkedin.
Filed under: Drug Discovery Services, Drug Safety Services, Preclinical Consulting Services |
Posted by Theresa Gralinski, Marketing Director at CorDynamics on August 08th, 2012
In my mind, the pharmaceutical and biotech industry can be reduced down to one elegant equation: good science + good business decisions = good drug development.
As the marketing director for CorDynamics, I spend a lot of my time discussing our innovative preclinical cardiovascular drug discovery and drug safety models. It’s our reason for being. My job is to communicate our capabilities and the good science we generate to clients, colleagues and potential customers.
Good Science=Good Business Decisions
As a member of the Healthcare Business Women’s—Chicago Chapter I’ve attended a number meetings led by dynamic senior healthcare and pharmaceutical executives discussing how to navigate our changing industry.
After each of these events, my underlying takeaway is that tough business decisions can be made easier when armed with good science.
When the science is solid and reliable—in our case from a cardiovascular drug discovery and drug safety side—it can be a useful guide for folks faced with extreme budget and timeline constraints.
It’s our job as the cardiovascular CRO, to understand the pressures on our clients as well as the need to be flexible, affordable and most importantly, collaborative in the work outsourced to us.
Good Science + Good Business Decisions = Good Drug Development
Filed under: Drug Discovery Services, Drug Safety Services |
Earlier this year, I flew 2,000 miles to be with an aging parent undergoing surgery. I tried not to think of all the science, education and yes, business decisions that would go into this one procedure. All went well. As I headed to the pharmacy to pick up the prescriptions necessary to inspire a full recovery and greater wellness, I walked away with tangible proof of my theory.
Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on July 29th, 2011
I recently attended a Fierce Biotech webinar about Special Studies in Cancer Patients and Cardiac Safety. The presentation covered a wide range of solid information on cardiac safety as it relates to oncology clinical trials.
Time and again, we have clients wondering if they need to conduct thorough cardiovascular preclinical safety studies for oncology compounds. In most cases the answer is yes; and the panelists on the webinar agreed.
In fact, as the panelists discussed, preclinical data is crucial to driving the design of clinical trials in oncology programs. If, for example, in vivo preclinical studies indicated some cardiac toxicity or reduced cardiac function, this may warrant consideration of additional analyses such as echocardiograms or cardiac enzyme panels in the clinical program.
Oftentimes in the past, the nonclinical cardiovascular battery for oncology agents consisted of actions on a single ion channel and an in vivo cardiovascular assessment along with standard toxicology studies. This was in contrast to the comprehensive risk assessments submitted for the more ‘traditional’ drug targets, such as depression or anti-infective agents, to name a few.
The overriding thought process behind these data packages could usually be distilled in project team meetings to somewhat misplaced logic in isolation, such as ‘it [the compound] is for cancer’ or ‘these patients usually have more consequential things to worry about than CV effects’.
While on some level those statements may occasionally be appropriate, recent events prove once again that the physiological processes controlling both cancerous and normal cells are not entirely discrete. These events also serve to demonstrate the unintended clinical consequences of truncated early development.
As one of the cardiology panelists noted – we need to be both efficient, yet cautious, in our design of oncology clinical trials regarding the issue of cardiac safety. Since we often don’t fully understand the off-target consequences of interfering with cancer mechanisms, it is prudent to provide as much useful information a priori (from preclinical studies) to rationally design these trials.
Filed under: Drug Safety Services |