Large Study Finds Favorable Risk-Benefit Profile For The New Anticoagulants Reply

A very large new meta-analysis finds a favorable risk-benefit for the new oral anticoagulant drugs in the setting of atrial fibrillation. The findings, published online in the Lancet, were remarkably consistent for all four of the new agents which have been fighting to replace warfarin, which was the only oral anticoagulant available for decades until the arrival of the new agents. Although warfarin is inexpensive, it has numerous interactions with other drugs and foods and requires regular monitoring and dose adjustments. The new agents can be taken once or twice a day and do not require dose changes.

Christian Ruff and colleagues combined data from the nearly 72,000 patients randomized in the four large mega-trials: RE-LY, which studied dabigatran (Pradaxa, Boehringer-Ingelheim); ROCKET AF, which studied rivaroxaban (Xarelto, Johnson & Johnson); ARISTOTLE, which studied apixaban (Eliquis, Pfizer and BristolMyers Squibb); and ENGAGE-AF-TIMI 48, which studied edoxaban (Daiichi Sankyo).

Click here to read the full post on Forbes.

About these ads

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.

 

Faint PRAISE: 13 Year Delay In Publication Of A Major Clinical Trial Sparks Criticism Reply

13 years after first being presented the results of the PRAISE-2 trial finally have been published in JACC: Heart Failure. The trial itself is now largely irrelevant to current clinical practice, as the hypothesis it tested has long been abandoned, but the long delay in publication may serve to bring even more awareness to the issue of the delay or complete absence of publication of many clinical trials.

An accompanying editorial, by Marc Pfeffer and Hicham Skali, is highly critical of the delay:

Although standards for conduct and reporting of clinical trials have improved since 2000, the failure to fully vet the results of a clinical trial of human volunteers in a peer-reviewed journal was and remains unacceptable.

PRAISE-2 had its origins in the first PRAISE trial, which was first presented in 1995 and subsequently published in the New England Journal of Medicine in 1996. In that trial there was no difference between amlodipine (Norvasc, Pfizer) and placebo in the rate of mortality or cardiovascular hospitalization in patients with heart failure. However, a prespecified subgroup analysis turned up the highly surprising result that heart failure patients with a nonischemic etiology who received amlodipine had a highly significant 46% reduction in the risk of death compared with placebo patients.

Click here to read the full post on Forbes.

Milton Packer

Milton Packer

New Anticoagulant Found Safe And Effective In Acute Venous Thromboembolism 1

In a large clinical trial the new oral anticoagulant apixaban (Eliquis, Pfizer and Bristol-Myers Squibb) was at least as effective as standard therapy and caused fewer bleeding complications in patients with acute venous thromboembolism. The results of the AMPLIFY (Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy) trial are being presented on Monday at the annual meeting of the International Society on Thrombosis and Haemostasis in Amsterdam and are being published in the New England Journal of Medicine. (The embargo on the trial was lifted early by the Journal after being broken by Reuters.)

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.

Danish Study Finds No Increased CV Risk With Azithromycin In General Population Reply

A large observational study found no increased risk for cardiovascular events associated with azithromycin (Zithromax, Pfizer) in a general population of young and middle-age adults. In a paper published  in the New England Journal of Medicine, Danish investigators report the results of a large national observational study comparing people who took azithromycin with matched controls who took no antibiotics and with matched controls who took penicillin V for similar indications.

Although there was a significant increase in the risk of death from cardiovascular causes in people taking azithromycin compared with people taking no antibiotics (RR 2.85, CI 1.13 – 7.24), there was no increase in risk when compared to people taking penicillin V (RR 0.93, CI 0.56 to 1.55). The findings, write the authors, indicate “that the increased risk that was observed in the comparison with no antibiotic use was entirely attributable to the risk of death associated with acute infection (or some other adverse health characteristic in persons receiving antibiotic treatment, as compared with those not treated with antibiotics) rather than with its treatment.”

Click here to read the full story on Forbes.

Blood Sample Mismatch Leads ‘Anguished’ Authors To Retract Three Lipitor Papers 1

Three substudies of the influential TNT (Treating to New Targets) trial have been retracted after the sponsor of the trial, Pfizer, discovered that blood samples from the study had been matched to the wrong participants.

The main results of TNT, published in 2005 in the New England Journal of Medicine, had a major impact on clinical practice and statin prescription patterns. The trial supported the increasingly aggressive use of statins and helped to solidify the enormous commercial success of atorvastatin (Lipitor, Pfizer).

The 3 newly-retracted substudies do not appear to affect the main finding of TNT. Two papers were published in the Journal of the American College of Cardiology. The third was published in the American Heart Journal. (The AHJ retraction notice has not yet been published, but the editors have confirmed the retraction.) Here are the 3 retracted articles:

Click here to read the full story on Forbes:

 

English: A package and pill of atorvastatin 40...

The Big Gamble of CETP Inhibitors 2

Merck has invested a substantial amount of money on the CETP inhibitor anacetrapib. Chemist and veteran pharma blogger Derek Lowe suspects that the company might as well have plunked the money down in a casino.

In a provocative new post, Lowe wonders if big pharma, in its desperation, has abandoned rational research in favor of, essentially, gambling. He notes that CETP is “a drug target that has incinerated a lot of money over the years” and wonders whether any of the compounds will “ever make it as a drug?” The failure of past CETP inhibitors, torcetrapib (Pfizer) and dalceptrapib (Roche), along with the recent failure of Tredaptive (Merck), “illustrate how little we know about this area [HDL].”

Read the rest of the post on Forbes.

 

FDA Approves Eliquis (Apixaban) For Stroke Prevention In AF 2

The FDA has finally approved apixaban (Eliquis, Bristol Myers Squibb and Pfizer) to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. The action comes after the widely-anticipated drug had been plagued by delays at the FDA but well before the PDUFA deadline of March 17, 2013. Eliquis is the latest member of the new generation of oral anticoagulants, which also includes dabigatran (Pradaxa, Boehringer Ingelheim) and rivaroxaban (Xarelto, Johnson & Johnson).

The FDA said that apixaban should not be taken by patients with prosthetic heart valves or by patients with AF caused by a heart valve problem. (Recently the FDA added a contraindication to the dabigatran label against using the drug in patients with mechanical heart valves.) The FDA said that the most serious risk associated with apixaban, as with other anticoagulants, is bleeding, including life-threatening and fatal bleeding. Patients taking apixaban will receive a patient Medication Guide. The FDA is advising health care professionals to counsel patients about the signs of symptoms of possible bleeding.

The FDA approval was based largely on the results of the highly positive ARISTOTLE trial which found that apixaban was superior to warfarin in AF patients. The FDA will likely allow BMS and Pfizer to claim that apixaban is superior to warfarin, as the press release states that “patients taking Eliquis had fewer strokes than those who took warfarin.”

Click here to download a PDF of the package insert.

Click here to read the FDA press release…