Possible New Lease On Life For Two Cardiology Drugs From Merck And J&J Reply

Early next year an FDA panel will review a new drug from Merck and a new indication for Xarelto (rivaroxaban), Johnson & Johnson’s highly successful new oral anticoagulant. Both drugs have had a rocky road getting to this stage and their success is by no means assured, but the announcement of the meeting of the FDA’s Cardiovascular and Renal Drugs Advisory Committee suggests that the companies have made progress resolving earlier problems.

Merck’s new drug application for vorapaxar (Zontivity is the proposed trade name) will be discussed on January 15 for the proposed indication of reduction of atherothrombotic events in patients with a history of myocardial infarction (MI).

On January 16 the panel will discuss the supplemental new drug application for J&J’s Xarelto (rivaroxaban) to reduce the risk of thrombotic cardiovascular events in patients in the first 90 days after suffering acute coronary syndrome.

Click here to read the full story on Forbes.

English: Logo of the .

About these ads

FDA Panel Gives Support To Novel Stroke Prevention Device From Boston Scientific Reply

The FDA’s Circulatory System Devices Panel yesterday gave a vote of confidence to Boston Scientific’s Watchman left atrial appendage closure device for the prevention of stroke in atrial fibrillation patients. By a large majority the panel agreed that the device was effective, that it was safe, and that the benefits outweighed the risks. In each case the vote was 13-1.

Click here to read the full story on Forbes.

 

Watchman_2

 

 

 

Boston Scientific May Face A Tough FDA Panel Reply

On Wednesday the FDA’s Circulatory System Devices Panel will once again review Boston Scientific’s Watchman left atrial appendage closure device for the prevention of stroke in atrial fibrillation patients (click here for the meeting materials). The panel will be the latest chapter in the long and contentious story of the Watchman. In 2010 the FDA issued a complete response letter and earlier this year a scandal broke out when the American College of Cardiology cancelled a prestigious late-breaking clinical trial presentation of the PREVAIL trial after the company broke an embargo by giving trial results to investors.

Wells Fargo analyst Lawrence Biegelsen predicts that the panel will be “contentious” but that ultimately the device will be approved next year. Although the trial missed one of its three c0-primary endpoints, the FDA reviewers emphasis on “the totality of the data” suggests a more benign FDA perspective, he writes.

One knowledgeable observer, Sanjay Kaul, who has served on several FDA panels, thinks the panel will indeed be contentious….

Click here to read the full post on Forbes.

 

Sanjay Kaul
Sanjay Kaul

 

Can Personalized Medicine And An Adaptive Trial Design Salvage This Hard Luck Drug? Reply

Arca Biopharma today announced that it had received FDA clearance to start a phase 2B/3 trial of its novel beta-blocker, Gencaro (bucindolol) for the prevention of atrial fibrillation in patients with heart failure. The GENETIC-AF trial has all the hallmarks of the modern era: the drug will only be tested in patients with a genetic variation that the company believes may predict a positive response to the drug. And the trial will be one of the first to utilize the much-discussed “adaptive” trial design, starting as a phase 2B study and then possibly expanding to a phase 3 study after an interim analysis of the trial data.

But if GENETIC-AF represents the very model of a modern drug, it also serves as a good example of the pitfalls of drug development. Because this drug has been around for a very long time and has had a very troubled history.

Click here to read the full story on Forbes.

 

Michael Bristow, Arca Biopharma President and CEO

 

FDA Removes Restrictions On Avandia Reply

In a remarkable climax to a long-running drama, the FDA today lifted major restrictions on rosiglitazone (Avandia, GlaxoSmithKline). The drug has been the subject of  intense criticism and controversy since the 2007 publication of the famous Nissen meta-analsysis that first raised the possibility that the blockbuster diabetes drug might increase the risk of heart attack and cardiovascular death.

The FDA said its actions were “consistent with the recommendations of expert advisory committees.” In June of this year an FDA panel reviewed re-adjudicated data from the RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) trial and concluded that the trial had not found an elevated risk of heart attack or death associated with rosiglitazone.

Click here to read the full post on Forbes.

 

FDA Spanks 23andMe, Grants Breakthrough Status To Factor Xa Inhibitor, and Approves Promus Premier Stent Reply

It was a busy morning at the FDA. Three new FDA actions may be of considerable interest in the cardiology universe:

FDA Halts 23andMe Personal Genome Test– The FDA sent a scathing letter to 23andMe ordering the company to stop selling its Personal Genome Service (PGS) test.   The FDA highlighted two cardiology-related uses of PGS as “particularly concerning,” including drug responses involving warfarin sensitivity and clopidogrel response.

FDA Grants Breakthrough Status To Factor Xa Inhibitor Antidote–

 …

FDA Approves Promus Premier Everolimus-Eluting Platinum Chromium Coronary Stent System–

Click here to read the full story on Forbes.

 

 Image representing 23andMe as depicted in Crun...

Image representing Portola Pharmaceuticals as ...

No Evidence That Statins Impact Cognitive Function Reply

In 2012 the FDA revised the label of statins to include a warning about reports that the drugs had been linked to memory loss or confusion. The FDA action appeared to be based largely on case reports. Despite concerns about this topic that have appeared sporadically in recent years, no high-quality review of the topic has appeared until now. In a paper published in Annals of Internal Medicine, Karl Richardson and colleagues report on a systematic review of the literature to assess the effect of statins on cognitive function.

The authors reviewed 25 trials, including randomized, controlled trials and cohort, case-control, and cross-sectional studies, that evaluated cognition in patients taking statins.

Their review found little evidence to support any adverse effect on cognitive function:

Click here t read the full story on Forbes.

 

No Evidence That Statins Impact Cognitive Function Reply

In 2012 the FDA revised the label of statins to include a warning about reports that the drugs had been linked to memory loss or confusion. The FDA action appeared to be based largely on case reports. Despite concerns about this topic that have appeared sporadically in recent years, no high-quality review of the topic has appeared until now. In a paper published in Annals of Internal Medicine, Karl Richardson and colleagues report on a systematic review of the literature to assess the effect of statins on cognitive function.

The authors reviewed 25 trials, including randomized, controlled trials and cohort, case-control, and cross-sectional studies, that evaluated cognition in patients taking statins.

Their review found little evidence to support any adverse effect on cognitive function:

“… low-quality evidence suggested no increased incidence of Alzheimer disease and no difference in cognitive performance in procedural memory, attention, or motor speed. Moderate-quality evidence suggested no increased incidence of dementia or mild cognitive impairment, nor any change in cognitive performance related to global cognitive performance scores, executive function, declarative memory, processing speed, or visuoperception.”

In a second analysis of the FDA post-marketing surveillance databases, the investigators found similar reporting rates for cognitive-related adverse events for statins and two other widely used drugs, losartan and clopidogrel.

The reviewers noted, however, that much of the data were not high quality and, in particular, there was a sparsity of data for high-dose statins, which are increasingly used.

They concluded that the available evidence does not support concerns linking statin use to cognitive impairment. “Larger and better-designed studies are needed to draw unequivocal conclusions about the effect of statins on cognition.”

 

The Fate Of New Cholesterol Drugs Depends On IMPROVE-IT Reply

Prospects for the highly anticipated new class of cholesterol-lowering drugs, the PCSK9 inhibitors, took a wild roller coaster ride this week. The publication of new lipid guidelines by the American Heart Association and the American College of Cardiology led many observers to think that the promising new drugs under development by Regeneron (in partnership with Sanofi), Amgen, and Pfizer might suffer significant delays.

The guidelines delivered a strong statement questioning the increasingly controversial theory that LDL lowering by itself is beneficial. “We found that non-statin therapies really didn’t provide an acceptable risk reduction benefit compared to their potential for adverse effects in the routine prevention of heart attack and stroke,” said the co-chair of the guideline. This led many observers to think that the FDA would likely require the developers of PCSK9 inhibitors to complete cardiovascular outcome trials before getting US approval. This decision would delay approval for several years.

Then, on Thursday, the companies developing PCSK9 inhibitors received some apparent good news. Bloomberg News reported that an FDA official said that the drugs “will only have to meet the U.S. Food and Drug Administration’s existing standards for clearance, including whether they cut cholesterol and reduce blood pressure or inflammation.”

But then the FDA added one other very important caveat. Here’s how they phrased it to me:

Click here to read the full post on Forbes.

 

FDA Approves Abbot’s MitraClip For Patients At Prohibitive Surgical Risk Reply

The FDA today approved Abbott’s catheter-based MitraClip device for patients with significant symptomatic degenerative MR who are at prohibitive risk for mitral valve surgery. The company said it would launch the device immediately in the United States. The device is the first percutaneous nonsurgical therapy approved for the treatment of mitral valve disease.

Click here to read the full post on Forbes.

 

Mitraclip

 

FDA Approves First New Atherectomy Device In 20 Years Reply

The FDA today granted PMA approval to the Diamondback 360 Coronary Orbital Atherectomy System (OAS) for the treatment of severely calcified coronary arteries. Cardiovascular Systems, the manufacturer of the device, said that the OAS  was the first new coronary atherectomy system to receive FDA approval in 2 decades. The company said  it would begin a controlled launch of the device immediately, focusing initially on “a limited number of the top medical institutions in the United States.”

In separate news, Medtronic yesterday announced the launch of its Export Advance aspiration catheter for coronary thrombus removal. The device was recently approved by the FDA. The company said the device features a pre-loaded stylet that “increases the deliverability and kink resistance of the new device while traversing the vasculature to reach the aspiration site.”

Click here to read the full post on Forbes.

FDA Approves New Pulmonary Hypertension Drug From Actelion Reply

The FDA today approved macitentan (Opsumit, Actelion), a new oral endothelin-receptor antagonist that is an enhanced version of the company’s bosentan (Tracleer). The drug is indicated to delay disease progression in patients who have pulmonary arterial hypertension (WHO Group I).

Click here to read the full post on Forbes.

 

Actelion

First Leadless Pacemaker Gains Approval In Europe Reply

St. Jude Medical announced on Monday that the world’s first leadless pacemaker had gained CE Mark approval in Europe. The company also announced that it was buying Nanostim, the company that developed the innovative device. The FDA recently granted conditional approval for an Investigational Device Exemption (IDE) application and a pivotal clinical trial, St. Jude also reported.

Click here to read the full story on Forbes.

 

CardioMEMS Heart Failure Device Gets Mixed Reception From FDA Advisory Panel Reply

The FDA’s Circulatory System Devices Panel sent a mixed message to the FDA today about CardioMEMS Champion HF Pressure Measurement System.  The small implantable device provides provides daily pulmonary artery pressure measurements to guide physicians in their treatment of patients with congestive heart failure.

In December 2011 the same panel voted 9-1 that the device was safe, 7-3 that the device had not been shown to be effective, and 6-4 that the benefits did not outweigh the risks. Now, two years, later, the vote wasn’t much different: the panel agreed unanimously (11-0) that the device was safe; 7-4 that it had not been shown  to be effective, and 6-4-1 that the benefits outweighed the risks.

Click here to read the full story on Forbes.

 

CardioMEMS wireless sensor with quarter

 

Cardiovascular Outcome Studies in Diabetes Drugs Finally Arrive Reply

For many years critics have bemoaned the absence of outcome studies for the many diabetes drugs used to lower blood glucose levels. Now, finally, two large trials with different drugs have been presented at the European Society of Cardiology meeting in Amsterdam and published simultaneously in The New England Journal of Medicine. The good news is that the drugs appear safe. Both trials turned up no evidence for the adverse cardiovascular events that some had feared. The bad news is that neither drug appeared to improve cardiovascular outcomes, though cardiovascular disease is the cause of death in most people with diabetes.

SAVOR-TIMI 53

A total of 16,492 people with type 2 diabetes at high risk for a cardiovascular event were studied in SAVOR-TIMI 53. Participants were randomized to the DPP-4 inhibitor saxagliptin (Onglyza, Bristol-Myers Squibb and AstraZeneca) or placebo.

Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE)

In the EXAMINE trial, 5,380 people with a recent acute coronary syndrome (ACS) were randomized to alogliptin (Nesina, Takeda Pharmaceuticals) or placebo.

These trials represent the first round of FDA-mandated cardiovascular outcomes trials for diabetes drugs, a major result of the rosiglitazone controversy. In an accompanying perspective in NEJM, William Hiatt, Sanjay Kaul, and Robert Smith, all members of the FDA advisory committees that debated the fate of rosiglitazone, discuss the complicated recent history of diabetes drugs at the FDA.

Click here to read the full story on Forbes.

 

New Subcutaneous ICD Said To Pose ‘Existential Crisis’ For Older ICDs Reply

Last year the FDA approved Boston Scientific’s subcutaneous ICD, the first ICD that can defibrillate the heart without using leads threaded to the heart through the blood vessels. Those leads are the source of many sophisticated pacing features in today’s ICDs, but they are also the main source of ICD-related complications, and, in several well-publicized incidents, have forced the FDA and ICD companies to initiate recalls. Now a prominent cardiologist writes that the S-ICD poses an “existential crisis” for previous generations of ICDs.

FDA approval of the S-ICD was based on a pivotal trial designed to assess the device’s safety and effectiveness. Results of the trial have now been published in Circulation. In this nonrandomized trial, the S-ICD was successfully implanted in 314 patients out of 321 in whom the implnantation was attempted.

The S-ICD easily met the prespecified primary safety and efficacy endpoints:

Click here to read the full post on Forbes.

S-ICD+device+image_hires

FDA Panel Recommends Approval For Pulmonary Hypertension Drug From Bayer Reply

The FDA’s Cardiovascular and Renal Drugs Advisory Committee recommended approval for Bayer’s new pulmonary hypertension drug, riociguat. The committee voted 11-0 in favor of approving the drug for two forms of pulmonary hypertension: pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTPH).

Click here to read the full story on Forbes.

 

 

 

 

FDA Warns That Popular Blood Pressure Drug Can Cause Severe Diarrhea Reply

The FDA is warning that the widely-used antihypertensive agent olmesartan (marketed as Benicar, Benicar HCT, Azor, Tribenzor, and generics) may cause severe diarrhea. According to an FDA safety announcement, olmesartan “can cause intestinal problems known as sprue-like enteropathy. Symptoms of sprue-like enteropathy include severe, chronic diarrhea with substantial weight loss.” The warning is being added to the label of drug products containing olmesartan. Olmesartan is a member of the class of drugs known as angiotensin II receptor blockers (ARBs).

The FDA said that it has found no evidence that other angiotensin II receptor blockers increase the risk for sprue-like enteropathy.

The FDA recommends that physicians tell their patients taking olmesartan to contact them if they develop severe, chronic diarrhea with substantial weight loss. Symptoms may take months or years to develop after initiation of olmesartan therapy. The FDA advises physicians to look for other causes of the symptoms, including celiac disease. Olmesartan should be replaced with another antihypertensive agent if no other cause is found.

FDA Turns Back New Indication For Rivaroxaban To Prevent Stent Thrombosis In ACS Patients Reply

Johnson & Johnson said today that it had received a complete response letter from the FDA for the supplemental new drug application for rivaroxaban (Xarrelto) for the prevention of stent thrombosis in patients with acute coronary syndromes (ACS). Earlier this year the FDA turned down for the second time the sNDA for the  general use of rivaroxaban to treat ACS patients.

Click here to read the full story on Forbes.

 

English: Logo of the .

 

 

Novel Heart Failure Drug From Novartis Gains ‘Breakthrough Therapy’ Designation From FDA 1

Serelaxin, the novel therapy under development for the treatment of acute heart failure, has received a “breakthrough therapy” designation from the FDA, according to Novartis, the company developing the drug. The designation, the FDA explains, “is intended to expedite the development and review of drugs for serious or life-threatening conditions” and requires “preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.” In addition to getting a speedier review process, the sponsor of a drug with the designation receives “more intensive FDA guidance” on the development program.

Click here to read the full story on Forbes.

 

Roller Coaster Path To Approval For Eliquis Uncovered By FDA Documents Reply

After the presentation and publication of the pivotal ARISTOTLE trial,  the novel anticoagulant apixaban (Eliquis, Pfizer and BristolMyers Squibb) was widely expected to be  a blockbuster. But then it got bogged down at the FDA where initial hopes for a speedy approval were dashed after highly critical reviews. Ultimately approval of the drug was delayed for 9 months past the original deadline as a result of both a PDUFA date extension and a complete response letter from the FDA. Now an article by Sue Sutter in  Pharmaceutical Approvals Monthlybased on documents posted by the FDA on its website, offers an inside look at the drug’s roller coaster ride through the FDA.

The article describes in detail the efforts of the FDA to investigate evidence of fraud and dispensing errors in ARISTOTLE. As Sutter writes: “To many looking in from the outside, the apixaban NDA filing seemed like a sure thing.” Initial results of ARISTOTLE suggested that it had “the potential to be best-in-class if the published ARISTOTLE data were to be believed.”

Click here to read the full story on Forbes.

Top Line Results: No Cardiovascular Benefits Found For Saxagliptin Reply

Top line results of a large phase 4 study with saxagliptin (Onglyza, Bristol-Myers Squibb and AstraZeneca) demonstrate that the drug is safe but has no cardiovascular benefits. AstraZeneca and Bristol-Myers Squibb today announced the top line results for the SAVOR-TIMI-53 Cardiovascular Outcomes Trial of Onglyza®. The full results are scheduled to presented at the  annual meeting of the European Society of Cardiology in Amsterdam on September 2 by Deepak Bhatt.

Click here to read the full story on Forbes.

 

FDA Raises Concerns About The Cybersecurity Of Medical Devices Reply

The FDA has raised concerns about the vulnerability of medical devices to cyberattack. In one dramatic instance, reported by the Wall Street Journal, a VA catheterization laboratory in New Jersey was temporarily closed after malware infected the lab’s computer devices.

 

Halamka offered some additional perspective on the problem to the Washington Post:

“There’s almost no medical device that doesn’t have a network jack on the back. To fight the evils of the Internet, not only do you have to have a moat, you have to have a drawbridge, burning oil to pour on attackers, and guys with arrows.”

Click here to read the full story on Forbes.

 

FDA Advisory Panel Backs Looser Restrictions On Avandia Reply

After two days of deliberation an FDA advisory panel today recommended that the severe restrictions (REMS) placed on rosiglitazone (Avandia, GlaxoSmithKline) be modified. The vote constitutes a modest revival in fortune for the embattled drug and its maker after many years of controversy and bad news.

Only 5 panel members voted to continue the current severe restrictions. One member (the consumer representative) voted for the withdrawal of rosiglitazone. By contrast, 20 members voted to either modify (13 votes) or remove (7 votes) the REMS. But the vote should not be interpreted as a broad statement by the panel that rosiglitazone is safe. Panel members made clear that they still had concerns about the safety of the drug. But their concerns were less pressing than in the past.

Click here to read the full story on Forbes.

 

 

With One Big Exception FDA Reviewers Back More Benign View Of Avandia Trial Reply

 

The FDA today released a 538-page briefing document for an advisory panel meeting on Wednesday and Thursday that will reassess a key clinical trial and reconsider the fate of the now-tarnished former blockbuster diabetes drug rosiglitazone (Avandia, GlaxoSmithKline). (Click here for the FDA documents.) As reported last week, the re-adjudication of the RECORD safety trial performed by the Duke Clinical Research Institute (DCRI) confirmed the initial finding of the trial that rosiglitazone was not associated with an increased risk for cardiovascular events.

 

For the most part, the FDA documents released today express strong support for the DCRI re-adjudication. But one FDA official, Thomas Marciniak, remains highly critical of RECORD  and says the trial data and, therefore, the analysis of the data from GSK and DCRI are completely unreliable. All parties agree, however, that the fundamental underlying design flaws of RECORD–  in particular, it’s open-label design– mean that data from the trial will never provide definitive assurance about the safety of rosiglitazone.

 

One FDA reviewer said the DCRI review of the mortality results in RECORD was “well-conceived and comprehensive” and “no stone was left unturned.” But the same reviewer states:

 

There is no amount of analytical rigor that can compensate for a weak trial design that is exacerbated by elements of poor execution, both of which afflicted RECORD. Its open- label non-inferiority design was simply problematic, especially for ascertainment of non-mortality MACE during trial execution…. Thus, while we agree with the analytical findings of the DCRI mortality re-analysis, we would emphasize that RECORD’s design irreparably hampers its ability to characterize definitively the CV risk of rosiglitazone.

 

The panel may well accept the findings of the re-adjudication and the FDA analysis. In that case the terrifying specter looming over the FDA and the rest of the medical establishment– that not just rosiglitazone but the entire drug development and approval process was fundamentally flawed and unreliable– will be put to rest, at least for now.

 

A Bitter Feud

 

Buried in the massive document is a bitter feud between an FDA rebel, Thomas Marciniak, and his bosses and other senior officials in the FDA’s drug division….

Click here to read the full story on Forbes.

 

Fda