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Xarelto EOD Media Report 10/13/16
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U.S. FDA clears Xarelto blood thinner despite faulty trial device
Oct 11, 2016 | Reuters
The U.S. Food and Drug Administration on Tuesday said it has determined the widely-used blood thinner Xarelto to be safe and effective for patients with the heart condition atrial fibrillation after serious doubts arose over the major study used to gain approval of the drug. -
Janssen's Blood Thinner Safe Despite Faulty Device in Study: FDA
Oct 13, 2016 | Bloomberg BNA
By Jeannie Baumann
A faulty device used in a clinical trial of Janssen Pharmaceutical Co.'s Xarelto doesn't change the FDA's conclusion that the blood thinner is an acceptable alternative to warfarin. The Food and Drug Administration released a report Oct. 11 on the impact on the trial outcome of using Alere's INRatio, a device used to calibrate and monitor doses of the blood thinner warfarin. -
FDA Finds Faulty INR Monitor Did Not Affect ROCKET AF Results
Oct 13, 2016 | Medscape
By Deborah Brauser
The faulty device used in the ROCKET AF trial to monitor anticoagulation in patients randomly assigned to receive warfarin compared with the group receiving rivaroxaban (Xarelto, Bayer/Johnson & Johnson) did not significantly affect the trial's overall results, the US Food and Drug Administration (FDA) concludes in a statement posted on its website. -
Five things for pharma marketers to know: Thursday, October 13, 2016
Oct 13, 2016 | Medical Marketing & Media
By Kevin McCaffrey
Brief discussion of the FDA analysis included in Medical Marketing & Media’s “Five things for pharma marketers to know.” Relevant portion highlighted below. -
FDA Says Xarelto Blood Thinner Is Safe (JNJ)
Oct 13, 2016 | Investopedia
By Shobhit Seth
The U.S. Food And Drug Administration (FDA) recently cleared the blood-thinning drug, Xarelto (rivaroxaban), declaring it to be safe and effective for patients with atrial fibrillation (AF) heart condition. AF is an irregular rapid heart rate that causes poor blood flow. Untreated AF patients have a five-fold increase in stroke risk. -
Pharmalot, Pharmalittle: New bill would create review board for drug prices
Oct 13, 2016 | STAT News
By Ed Silverman
Brief discussion of the FDA announcement in the STAT News morning roundup of news. Relevant portion highlighted below. -
FDA approves Xarelto to treat heart patients after clinical trial concerns
Oct 12, 2016 | Becker’s Hospital Review
By Mackenzie Bean
The Food and Drug Administration approved the use of the blood thinner drug Xarelto to treat patients with atrial fibrillation, or irregular heartbeat, reports Reuters. Xarelto, first approved in 2011, is used to treat or prevent blood clots and lower the risk of stroke. -
FDA Concludes Xarelto Blood Thinner Is Safe and Effective Despite Faulty Trial Device
Oct 12, 2016 | Managed Care Magazine
In July 2016, the hand-held, point-of-care INRatio device (Alere, Inc.) was recalled because of the potential to generate inaccurate results. This device was used to monitor warfarin therapy in the control group of the pivotal ROCKET-AF trial, which provided the primary data to support the 2011 approval of the blood-thinner rivaroxaban (Xarelto, Janssen). -
FDA review confirms rivaroxaban’s safety, efficacy in patients with atrial fibrillation
Oct 12, 2016 | Cardiovascular Business
By Tim Casey
After a thorough review, the FDA has concluded that rivaroxaban (Xarelto) is a safe and effective alternative to warfarin in patients with atrial fibrillation. -
FDA: ROCKET AF results not affected by faulty INR monitoring device
Oct 12, 2016 | Healio
The FDA announced that its analysis of the impact of a faulty INR monitoring device on the outcomes of the ROCKET AF trial of rivaroxaban concluded that the effects of the device on outcomes were minimal and that rivaroxaban remains safe and effective. The point-of-care monitoring device (INRatio, Alere) was used in ROCKET AF, the pivotal trial of rivaroxaban (Xarelto, Janssen Pharmaceuticals) vs. warfarin for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. INR monitoring is necessary in patients assigned warfarin. -
No Change to Rivaroxaban's Label Despite Faulty Monitoring Device
Oct 12, 2016 | NEJM
By Kelly Young
An FDA analysis has found that a faulty, point-of-care device used to monitor international normalized ratio did not substantially alter the results of the ROCKET AF trial, which led to the 2011 approval of the anticoagulant rivaroxaban (Xarelto). -
US FDA Declares Xarelto Blood Thinner Safe Despite Lawsuits
Oct 12, 2016 | iTechPost
By Rodney Rafols
Xarelto is a blood thinner used for patients with the heart condition atrial fibrillation. The treatment is used to prevent strokes among patients who have the condition, as they have five times the risk of having a stroke without treatment. However, manufacturers of the treatment also face lawsuits after patients experienced side effects from its use. -
Countering Xarelto critics, FDA backs clot-buster's benefits despite study's faulty device
Oct 11, 2016 | FiercePharma
By Carly Helfand
Johnson & Johnson and Bayer can breathe easy: The FDA declared Wednesday that a faulty device didn't distort the results of a key Xarelto trial. In the wake of questions about Xarelto's crucial atrial fibrillation trial, the agency said it’s “quite likely” that the later-recalled monitoring device prompted higher-than-usual doses of the old-guard therapy warfarin in the trial. That's the treatment Xarelto topped in the Phase III study, ROCKET AF. -
FDA Lifts Cloud Over J&J’s Xarelto With ROCKET-AF Re-Analysis
Oct 11, 2016 | Pink Sheet
By Sue Sutter
An FDA re-analysis of the ROCKET-AF trial of Janssen Pharmaceutical Cos.’s Xarelto (rivaroxaban) appears to close the books on the troubled, Robert Califf-led study by recommending against any labeling changes for the anticoagulant. On Oct. 11, FDA announced the Division of Cardiovascular and Renal Products had reaffirmed the safety and efficacy of rivaroxaban as an alternative to warfarin in atrial fibrillation patients after completing a variety of analyses to assess the impact of a faulty coagulation monitoring device used in ROCKET-AF. -
FDA Says Faulty Device Didn't Affect Xarelto Trial Results
Oct 11, 2016 | Law360
By Shayna Possess
Blood thinner Xarelto is a safe and effective treatment for patients with a type of irregular heartbeat called atrial fibrillation despite recent concerns regarding the clinical trial that was key to securing the medication’s approval, the U.S. Food and Drug Administration said Tuesday. -
FDA: ROCKET AF Results Not Affected by Faulty INR Testing in Warfarin Arm
Oct 11, 2016 | TCTMD
By Michael O'Riordan
The US Food and Drug Administration (FDA) has concluded that inaccurate results from the point-of-care device used to measure international normalized ratio (INR) values in warfarin-treated patients as part of the ROCKET AF clinical trial did not materially affect the study’s findings. -
FDA Reaffirms Safety And Efficacy Of Rivaroxaban
Oct 11, 2016 | CardioBrief
By Larry Husten
Following a year of controversy and uncertainty relating to the anticoagulant drug rivaroxaban (Xarelto, Johnson & Johnson), the FDA has reaffirmed the drug’s safety and efficacy. Rivaroxaban is approved for stroke reduction in patients with atrial fibrillation. The indication is based on results of the ROCKET-AF trial, which compared rivaroxaban to warfarin. New questions about the trial emerged last year when it became known that the portable device used to adjust warfarin usage in the trial had been recalled due to unreliability in some patient populations. -
FDA finds study data supporting Xarelto approval OK despite recalled Alere INRatio device
Oct 11, 2016 | Seeking Alpha
In a statement, the FDA reports that it has concluded that Johnson & Johnson's (JNJ -1.6%) blood thinner XARELTO (rivaroxaban) is a safe and effective alternative to warfarin in patients with atrial fibrillation. The agency conducted a variety of analyses on a Phase 3 study, ROCKET-AF, that supported the company's marketing application and 2011 approval. -
FDA sounds the all-clear for J&J blood thinner
Oct 13, 2016 | NJ.com
By Kathleen O'Brien
Johnson & Johnson's popular blood-thinning medication, Xarelto, is safe and effective despite earlier concerns about the research behind it, the U.S. Food and Drug Administration has ruled. The drug had come under a cloud after the FDA recalled a device that was used to measure the effectiveness of blood thinners in Xarelto's clinical trial. That trial showed the J&J drug to be better at preventing ischemic attacks than the more commonly prescibed drug, warfarin. -
FDA reaffirms anticoagulant drug rivaroxaban’s safety and efficacy
Oct 12, 2016 | News Tonight Africa
By Kehumile Mazibuko
Following an extended trial and uncertainty, the U.S. Food & Drug Administration (FDA) on Tuesday reaffirmed the anticoagulant drug rivaroxaban’s safety and efficacy. Rivaroxaban has been approved for reducing odds of stroke in patients with atrial fibrillation. The federal agency reaffirmed the drug’s safety and efficacy after the ROCKET-AF trial, which compared the controversial drug to warfarin.
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U.S. FDA clears Xarelto blood thinner despite faulty trial device
Oct 11, 2016 | Reuters
The U.S. Food and Drug Administration on Tuesday said it has determined the widely-used blood thinner Xarelto to be safe and effective for patients with the heart condition atrial fibrillation after serious doubts arose over the major study used to gain approval of the drug.
Xarelto, known chemically as rivaroxaban, won U.S. approval in 2011 after it was shown to be a safe and effective alternative to decades old warfarin for preventing strokes in a study of more that 14,000 patients with the irregular heartbeat condition. Without treatment, atrial fibrillation leaves patients five times more vulnerable to strokes.
In the study dubbed Rocket-AF, warfarin therapy was monitored using the Alere Inc INRatio device that has since been recalled over its potential to generate inaccurate results, casting a shadow over the value of the large, pivotal clinical trial.
"The FDA has completed a variety of analyses to assess the impact that this faulty monitoring device had on the Rocket-AF study results," the agency said in a statement posted on its website. "The Agency has determined that effects on strokes or bleeding, including bleeding in the head, were minimal."
Xarelto, a multibillion-dollar product, is sold by Bayer AG overseas and by Johnson & Johnson in the United States. It is the market leader in a popular new class of medicines designed to replace problematic warfarin, which requires a special diet and regular monitoring to make sure dosing remains within a limited therapeutic range to keep it from becoming either too low, which increases stroke risk, or too high, which greatly raises the risk of serious bleeding.
Warfarin, a widely used and inexpensive generic medicine, is also sold by Bristol-Myers Squibb under the brand name Coumadin. Bristol-Myers and Pfizer also sell the Xarelto rival Eliquis. (Reporting by Bill Berkrot; Editing by Bernard Orr)
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Janssen's Blood Thinner Safe Despite Faulty Device in Study: FDA
Oct 13, 2016 | Bloomberg BNA
By Jeannie Baumann
A faulty device used in a clinical trial of Janssen Pharmaceutical Co.'s Xarelto doesn't change the FDA's conclusion that the blood thinner is an acceptable alternative to warfarin.
The Food and Drug Administration released a report Oct. 11 on the impact on the trial outcome of using Alere's INRatio, a device used to calibrate and monitor doses of the blood thinner warfarin.
The analysis came after years of questions about the accuracy of INRatio test results, for which the FDA initiated recalls in 2014. Alere voluntarily withdrewINRatio in July “due to the potential to generate inaccurate results,” the FDA said. The Waltham, Mass.-based device maker also has been fighting a class action lawsuit over allegations that INRatio provides misleading results (10 LSLR 18, 9/16/16).
“Because of the concern about the Alere INRatio device, the FDA has completed a variety of analyses to assess the impact that this faulty monitoring device had on the ROCKET-AF study results. The Agency has determined that effects on strokes or bleeding, including bleeding in the head, were minimal,” the FDA said in an Oct. 11 statement about the report titled ROCKET AF Reanalysis Reviews. “The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation.” Janssen is a subsidiary of Johnson & Johnson.
The clinical trial that used the InRatio device, ROCKET AF, compared the then-experimental Xarelto (rivaroxaban) with warfarin, a blood thinner that has been on the market since 1954. Investigators in the ROCKET AF study found rivaroxaban was “noninferior”—or not worse than—warfarin, and the FDAapproved Xarelto in 2011 based on that study. ROCKET AF is short for Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation.
Califf Led Study While at Duke
FDA Commissioner Robert Califf, who was a cardiologist at Duke University before joining the agency, helped lead the study. He presented the study's results to an FDA advisory committee meeting in 2011, before he joined the agency in 2015.
Advocacy group Public Citizen has flagged Califf's role in the clinical trial and called on the FDA in a December 2015 letter to “further investigate the potentially dangerous situation involving a drug approval and the role of FDA Commissioner nominee Dr. Robert Califf, then Co-Chairman of the industry Steering Committee advising Johnson and Johnson on the study, especially his role in choosing the poorly-performing measuring device that was central to interpreting the study.”
Sidney M. Wolfe, founder and senior adviser of Public Citizen's Health Research Group, again noted Califf's role in the ROCKET AF clinical trial in an Oct. 12 interview with Bloomberg BNA.
“The larger issue is how many people died or were seriously injured or paralyzed” from the time it was “crystal clear” that the INRatio device was defective until it came off the market in July, Wolfe said. In March, Wolfe said during a presentation to the FDA that the ROCKET AF study and INRatio case highlights two overarching problems: the inadequacy of the FDA's low legal standard under Section 510(k) for determining that a device is substantially equivalent to already-approved devices that monitor life-threatening conditions; and the “dangerous failure of parties involved,” including the FDA's drug and device centers, the ROCKET AF investigators, Janssen and INRatio manufacturers.
Wolfe called on the FDA “to promptly investigate, communicate serious device warnings to all other parties and take appropriate, necessary actions.”
“The report that the FDA put out is narrowly focused” on whether using the defective InRatio device would have affected the agency's interpretation of the ROCKET AF study, Wolfe told Bloomberg BNA Oct. 12. But he said the agency made its conclusions “without enough data to really conclude as firmly as they have.”
Xarelto Decision Defended
FDA spokeswoman Sandy Walsh told Bloomberg BNA in an Oct. 12 e-mail that “The FDA conducted a thorough review and concluded that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation.” She also noted that “Dr. Califf was recused from this matter.”
In an Oct. 12 statement to Bloomberg BNA, Janssen spokeswoman Sarah Freeman said, “We’re pleased to see that the FDA’s reanalysis of the ROCKET-AF trial data confirms that the benefit-risk profile of XARELTO® (rivaroxaban) remains positive for reducing the risk of stroke in patients with non-valvular atrial fibrillation.”
“This conclusion comes directly after, and is in line with, the European Medicines Agency’s (EMA) recent review, which confirmed their original assessment, and with the independent reanalysis published in the New England Journal of Medicine,” Freeman said.
“Importantly,” she said, “the real-world performance of XARELTO® further supports these assessments. Since its approval in 2011, more than 23 million patients have been prescribed the medicine worldwide and one real-world study after another across its six approved indications continues to confirm XARELTO® is performing as expected.”
Alere spokeswoman Jackie Lustig declined to comment in an Oct. 12 e-mail to Bloomberg BNA.
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FDA Finds Faulty INR Monitor Did Not Affect ROCKET AF Results
Oct 13, 2016 | Medscape
By Deborah Brauser
The faulty device used in the ROCKET AF trial to monitor anticoagulation in patients randomly assigned to receive warfarin compared with the group receiving rivaroxaban (Xarelto, Bayer/Johnson & Johnson) did not significantly affect the trial's overall results, the US Food and Drug Administration (FDA) concludes in a statement posted on its website.
"The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation," the agency noted in the report.
The original ROCKET AF findings that rivaroxaban was noninferior to warfarin for stroke prevention in these patientswere published in 2011 and formed the basis for the FDA's approval of the drug 3 months later.
However, controversy has surrounded the international normalized ratio (INR) measuring device used in the trial to monitor warfarin administration. The Alere INRatio Monitor System was part of a class I recall by the FDA last year because of its "potential to generate inaccurate results," said the agency.
Others have suggested that the device could have made the warfarin results in the trial appear worse than they really were and that falsely low readings could have caused warfarin doses to be unnecessarily increased, which could in turn increase risk for bleeding.
Because of these concerns, the FDA conducted their own series of analyses to evaluate whether the device really did affect the ROCKET AF findings. Their investigators found that "the effects on strokes or bleeding, including bleeding in the head, were minimal."
In addition, they write in the summary of their 74-page report that "no changes in rivaroxaban labeling to reflect the impact of use of the INRatio device in ROCKET are warranted" and "no other major regulatory action should be taken with respect to rivaroxaban."
In a joint statement sent to Medscape Medical News, Bayer and Janssen, the pharmaceutical arm of Johnson & Johnson, note that the companies are "pleased to see that the FDA's reanalysis of the ROCKET-AF trial data confirms that the benefit-risk profile of Xarelto remains positive."
They add that the conclusion comes after and is line with a re-evaluation by the European Medicines Agency in September and a reanalysis of trial data published in Research Letters in The New England Journal of Medicine in February and July by ROCKET AF investigators and committee members, including Keith A.A. Fox, University of Edinburgh, Scotland.
When asked for comment, Dr Fox reiterated these points, telling Medscape Medical News via email that "the FDA findings are entirely consistent with what the Steering Committee found and published in the letters to the NEJM."
"Modest" Effects
The FDA's analyses included examining data for 7125 patients treated with warfarin in ROCKET. They found that readings from the INRatio device at a patient's point of care were almost 13% less than INR readings from a lab-based device at Duke University, Durham, North Carolina.
After use of "mathematical modelling approaches to estimate the clinical outcomes results that might have occurred in ROCKET if a more accurate INR assay has be used to guide warfarin dosing," three of the models predicted 7% to 10% lower expected rates of major bleeding in the warfarin group vs the 3.45 events per 100 patient-years that were observed in ROCKET.
"Overall, these estimated reductions in the rates of bleeding events in the warfarin arm were small enough so that the benefits of rivaroxaban would still outweigh the risks if efficacy were not affected," note the FDA's investigators.
They add that "it is quite likely that patients in the warfarin arm of ROCKET unintentionally received higher doses of warfarin than they would have received if the INRatio device had provided results similar" to those by the Duke lab–based device.
"However, the effects of this increased intensity of anticoagulation on clinical outcomes were likely to have been quite modest."
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Five things for pharma marketers to know: Thursday, October 13, 2016
Oct 13, 2016 | Medical Marketing & Media
By Kevin McCaffrey
1. Aetna announced it had signed a value-based deal with Merck for its two diabetes drugs, Janumet and Januvia. The rebates will be based on whether the drugs contribute to Type 2 patients achieving or maintaining their treatment goals.
2. New research expected to be published next week by the National Bureau of Economic Research estimates that co-pay coupons for 23 drugs with generic alternatives resulted in up to $2.7 billion in additional spending over five years. (NYT)
3. An FDA analysis found that the Alere INRatio — a device used to monitor warfarin therapy in patients — did not impact the results of a trial that informed the the FDA submission of Johnson & Johnson's Xarelto. The agency concluded that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation.
4. Rep. Rosa DeLauro (D-CT) proposed new legislation that would create a national board to “stop pharmaceutical companies from charging consumers excessive prices.” The board would collect data on drug prices and take enforcement action against drugmakers that charge excessive prices. The enforcement actions would include “shortening monopoly protections, imposing monetary fines, and recouping previous tax benefits for life saving treatments.”
5. The results of Eli Lilly's large clinical trial for its experimental Alzheimer's drug, solanezumab, are coming down the pike — with interim data expected to be released in the end of November. The drug failed in two previous trials. (STAT)
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FDA Says Xarelto Blood Thinner Is Safe (JNJ)
Oct 13, 2016 | Investopedia
By Shobhit Seth
The U.S. Food And Drug Administration (FDA) recently cleared the blood-thinning drug, Xarelto (rivaroxaban), declaring it to be safe and effective for patients with atrial fibrillation (AF) heart condition. AF is an irregular rapid heart rate that causes poor blood flow. Untreated AF patients have a five-fold increase in stroke risk.
Xarelto is a multi-billion dollar blood thinner developed and sold in the global markets by German giant Bayer AG, and by Johnson & Johnson (JNJ) in the United States. The prescription drug is used to reduce the risk of stroke and blood clots in people with atrial fibrillation not caused by a heart valve problem. It works by preventing blood clots from forming in the arteries and veins.Xarelto's Spotty History
Xarelto was approved in the U.S. in 2011 after it was found to be effective for stroke prevention in a study of 14,000 patients with atrial fibrillation.
However, during the study (dubbed "Rocket-AF") comparing Xarelto to warfarin, the warfarin therapy was monitored using the Alere Inc INRatio device, which was later found to report inaccurate results.
Despite the controversy surrounding this large, pivotal study, Xarelto was deemed a safe and effective alternative to decades-old warfarin, which required a strict diet and frequent monitoring.
Warfarin remains a cheaper generic drug offered by Bristol-Myers Squibb Co. (BMY) under the brand name Coumadin. Bristol-Myers and Pfizer Inc. (PFE) also sell the drug Eliquis, which directly competes with Xarelto.
Xarelto has been named in several major lawsuits, including one where a patient reported gastrointestinal bleeding after using the blood thinner, and another where a patient suffered a fatal cerebral hemorrhage a month after taking the drug.FDA Clearance
Notwithstanding its spotty past, the FDA declared Xarelto safe. “The Agency has determined that effects on strokes or bleeding, including bleeding in the head, were minimal,” the FDA said in a statement. “Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation.”
The FDA clearance will pave the way to boost Xarelto sales across the globe.
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Pharmalot, Pharmalittle: New bill would create review board for drug prices
Oct 13, 2016 | STAT News
By Ed Silverman
Hello, everyone, and nice to see you again after a brief respite. Although we made good use of our time away, we know the world continued spinning, so we have gathered a menu of tidbits that, hopefully, catch you up on a variety of events and doings. Meanwhile, we are easing back in with help of a few cups of stimulation — we are back to Cinnamon Dolce, by the way. So please join us and, of course, have a smashing day …
Representative Rosa DeLauro (D-Conn.) plans to introduce a bill called the Prescription Drug and Medical Device Review Board Act, which would establish an inter-agency panel to collect data on drug and device prices and manufacturing costs. In cases where manufacturers are found to charge excessive prices, penalties could include shortening monopoly protections, imposing fines, and recouping tax benefits for lifesaving treatments.
Pfizer plans to retract five papers by a former employee, after an investigation found images that were duplicated in each of the published articles, according to For Better Science. The former employee, Min-Jean Yin, had worked as a senior principal scientist since 2003 at Pfizer research facilities in La Jolla, Calif. Her LinkedIn profile indicates she joined Diagnologix last month as general manager.
Eli Lilly is racing to wrap up trial results of an Alzheimer’s drug, a closely watched experiment involving a treatment for delaying cognitive decline in patients with mild forms of the disease, STAT writes. The outcome has widespread implications not only for treatment, but for other drug makers and possibly even the US Food and Drug Administration, depending upon the strength of the results.
The FDA decided the widely used Xarelto blood thinner is safe and effective for patients with atrial fibrillation despite controversy over a key study used to gain approval of the drug. Concerns emerged last year after reports that a device for adjusting warfarin usage in the trial had been recalled due to unreliability in some patients and a BMJ report suggested Johnson & Johnson knew of accuracy concerns but withheld data from the agency.
Merck and Aetna signed a so-called value-based contracting deal for the Januvia type 2 diabetes treatment, the latest such arrangement in which insurance coverage is tied to patient outcomes. In this instance, the rebates that Merck pays to the insurer will be set based on the improvement seen in patients. Such deals are becoming more common as drug makers face pressure over their pricing.
Sun Pharmaceuticals is struggling to jump-start growth after its acquisition of Ranbaxy Laboratories dampened revenue in emerging markets and concerns over US drug prices make further deals questionable, Bloomberg News says. Meanwhile, Sun is recalling from the US 31,700 bottles of generic Wellbutrin extended-release tablets, which are used to treat depression, due to “failed dissolution specifications,” the Economic Times writes.
The FDA found a direct link between contaminated water at PharmaTech and a multi-state outbreak of B. cepacia, three months after the contract manufacturer recalled lots of Diocto Liquid, a docusate sodium solution, InPharma Technologist informs us.
A global shortage of a chemotherapy agent called etoposide, which is made by Bristol-Myers Squibb, is expected to last until April, news.com.au reports, citing Australia’s Therapeutic Goods Administration.
Synairgen says AstraZeneca stopped a mid-stage study for its lead drug candidate as a potential treatment for severe asthma, Reuters tells us.
The UK’s National Institute for Health and Care Excellence rejected Johnson & Johnson’s Imbruvica for treating a rare type of slow-growing non-Hodgkin’s lymphoma, PharmaTimes reports.
Celltrion says its biosimilar version of Rituxan has shown the same therapeutic effects as the originator drug in Phase 3 clinical trials, the Korea Herald tells us.
Roche says the FDA gave a priority review designation to its Lucentis medication as a treatment for choroidal neovascularization in patients with myopia, PMLivesays.
Pfizer suffered a setback in the UK after the Court of Appeal in London ruled against it in a patent case over the use of its Lyrica for pain relief, Reuters reports.
Amgen has sold a facility in Longmont, Colo., to AstraZeneca for $64.5 million, the second time in two months that Amgen has sold a Colorado plant to the drug maker, the Pacific Coast Business Times writes.
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FDA approves Xarelto to treat heart patients after clinical trial concerns
Oct 12, 2016 | Becker’s Hospital Review
By Mackenzie Bean
The Food and Drug Administration approved the use of the blood thinner drug Xarelto to treat patients with atrial fibrillation, or irregular heartbeat, reports Reuters.
Xarelto, first approved in 2011, is used to treat or prevent blood clots and lower the risk of stroke.
This summer, a device used to monitor the health of more than 14,000 patients in a clinical trial for the drug was recalled for its potential to generate inaccurate results. The recall left some members of the drug industry to question the accuracy of the drug study, called Rocket-AF, and whether the treatment should be used to treat atrial fibrillation patients.
However, the FDA issued a statement on its website saying it "completed a variety of analyses to assess the impact that this faulty monitoring device had on the Rocket-AF study results" and "determined that effects on strokes or bleeding, including bleeding in the head, were minimal."
New Brunswick, N.J.-based Johnson and Johnson sells Xarelto in the U.S., while Leverkusen, Germany-based Bayer maintains drug sales overseas, according to the report.
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FDA Concludes Xarelto Blood Thinner Is Safe and Effective Despite Faulty Trial Device
Oct 12, 2016 | Managed Care Magazine
In July 2016, the hand-held, point-of-care INRatio device (Alere, Inc.) was recalled because of the potential to generate inaccurate results. This device was used to monitor warfarin therapy in the control group of the pivotal ROCKET-AF trial, which provided the primary data to support the 2011 approval of the blood-thinner rivaroxaban (Xarelto, Janssen).
Because of the concern about the INRatio device, the FDA’s Center for Drug Evaluation and Research has completed a series of analyses to assess the affect that this faulty monitoring device may have had on the ROCKET-AF study results.
The agency has determined that effects of the device on strokes or bleeding, including intracranial bleeding, were minimal. The FDA concluded that rivaroxaban is a safe and effective alternative to warfarin in patients with nonvalvular atrial fibrillation.
The ROCKET-AF trial was a randomized, double-blind, event-driven, confirmatory study of rivaroxaban (n = 7,081) versus dose-adjusted warfarin (n = 7,090) in patients with nonvalvular atrial fibrillation. The study’s primary objective was to demonstrate that the efficacy of rivaroxaban for the intended indication––a reduction in the rate of stroke and systemic embolism––was noninferior to that of dose-adjusted warfarin. The proposed primary efficacy endpoint was the time to the first occurrence of stroke (any type) or non-CNS systemic embolism. The dosage of rivaroxaban was 20 mg once daily for most patients. The dosage was adjusted to 15 mg daily for patients with creatinine clearance (CrCL) of 30 mL/min to 50 mL/min; those with CrCL of less than 30 mL/min were excluded.
All study sites were instructed to use only the INRatio device to adjust the warfarin dose. Approximately 87% of patients in the warfarin arm had at least one same-day pair of international normalized ratio (INR) assays read with the INRatio device at the study site (point-of-care) as well as with a laboratory-based device at Duke University near the end of the trial. Most of these patients had two such pairs of INR readings.
The study’s primary endpoint was achieved in 3.8% of the rivaroxaban group and in 4.3% of the warfarin group (hazard ratio [HR], 0.88). The rates of all-cause mortality were 8.8% and 9.4% in the two groups, respectively. Major bleeding occurred in 3.6% of rivaroxaban-treated patients and in 3.5% of warfarin-treated patients (HR, 1.04).
After the INRatio device was recalled, the FDA modeled the affect of the device on clinical outcomes in the ROCKET-AF trial. The agency estimated that if a more-accurate device had been used, the rate of major bleeding in the warfarin arm might have been 7% to 10% less than observed, with correspondingly small changes in the rivaroxaban-versus-warfarin HR that would disfavor rivaroxaban. In addition, it was estimated that the HRs for life-threatening or fatal bleeding and hemorrhagic stroke, which both favored rivaroxaban numerically, would be minimally increased, but both would still favor rivaroxaban. In addition, the HR for ischemic stroke would be moderately changed in favor of rivaroxaban.
Sources: FDA(link is external); October 11, 2016; and ROCKET-AF Reanalysis(link is external); September 26, 2016.
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FDA review confirms rivaroxaban’s safety, efficacy in patients with atrial fibrillation
Oct 12, 2016 | Cardiovascular Business
By Tim Casey
After a thorough review, the FDA has concluded that rivaroxaban (Xarelto) is a safe and effective alternative to warfarin in patients with atrial fibrillation.
The FDA’s Oct. 11 announcement came three months after Alere voluntarily recalled its INRatio and INRatio 2 devices, which were used to monitor warfarin in the ROCKET-AF trial. Results of that study, which compared warfarin and rivaroxaban, supported the FDA approval of rivaroxaban in 2011.
When Alere acknowledged that the INRatio devices could lead to inaccurate results, the FDA performed several analyses to determine if the devices affected the findings of the ROCKET-AF study. The FDA said in a news release that “effects on strokes or bleeding, including bleeding in the head, were minimal.”
The FDA has approved rivaroxaban to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The agency said no labeling changes would be needed due to issues with the INRatio devices.
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FDA: ROCKET AF results not affected by faulty INR monitoring device
Oct 12, 2016 | Healio
The FDA announced that its analysis of the impact of a faulty INR monitoring device on the outcomes of the ROCKET AF trial of rivaroxaban concluded that the effects of the device on outcomes were minimal and that rivaroxaban remains safe and effective.
The point-of-care monitoring device (INRatio, Alere) was used in ROCKET AF, the pivotal trial of rivaroxaban (Xarelto, Janssen Pharmaceuticals) vs. warfarin for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. INR monitoring is necessary in patients assigned warfarin.
Alere had announced in December 2014 that INRatio and another of its monitoring systems should not be used by patients with characteristics such as abnormal hematocrit levels; raised fibrinogen levels and related conditions; and bleeding or bruising. Shortly afterward, the company reported the concerns to the FDA and began an investigation.
Post hoc analyses published in a letter to The New England Journal of Medicine determined that use of the Alere device did not affect the safety and efficacy outcomes of ROCKET AF. In July, Alere announced it waswithdrawing the monitoring systems from the market.
In its announcement, the FDA stated that “effects on strokes or bleeding, including bleeding in the head, were minimal. The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with [AF].”
Although analyses by the FDA and Janssen concluded that a lower bleeding rate would have been seen in patients from ROCKET AF assigned warfarin had a properly working monitoring device been used, “these estimated reductions in the rates of bleeding events in the warfarin arm were small enough so that the benefits of rivaroxaban would still outweigh the risks if efficacy were not affected,” Martin Rose, MD, JD, a reviewer for the FDA, wrote in the analysis.
In addition, he wrote, had the device worked correctly, more ischemic stroke events would have been reported in the warfarin arm, further confirming that the benefits of rivaroxaban outweigh its risks compared with warfarin.
Disclosure : Rose is an employee of the FDA.
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No Change to Rivaroxaban's Label Despite Faulty Monitoring Device
Oct 12, 2016 | NEJM
By Kelly Young
An FDA analysis has found that a faulty, point-of-care device used to monitor international normalized ratio did not substantially alter the results of the ROCKET AF trial, which led to the 2011 approval of the anticoagulant rivaroxaban (Xarelto).
The device was recalled because it gave falsely low readings. This raised concern that patients in the warfarin arm of the trial may have been over-anticoagulated and subject to increased bleeding risk.
The FDA analysis, announced on Tuesday, determined that "the effects on strokes or bleeding, including bleeding in the head, were minimal. The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation."
The agency did not recommend any changes to rivaroxaban's label.
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US FDA Declares Xarelto Blood Thinner Safe Despite Lawsuits
Oct 12, 2016 | iTechPost
By Rodney Rafols
Xarelto is a blood thinner used for patients with the heart condition atrial fibrillation. The treatment is used to prevent strokes among patients who have the condition, as they have five times the risk of having a stroke without treatment. However, manufacturers of the treatment also face lawsuits after patients experienced side effects from its use.
Despite the lawsuits, the U.S. Food and Drug Administration (FDA) has said that Xarelto is safe to use, according to Reuters. Xarelto has been made as a replacement for warfarin since the latter has since become ineffective.
Xarelto, however, isn't without any problems, since its manufacturers are currently facing lawsuits. The lawsuits stem from two cases. The first one is a man who has suffered gastrointestinal bleeding after taking Xarelto. The other case is that of a woman who had a fatal cerebral hemorrhage just one month after taking the medicine,Consumer Advocacy News stated in its report.
The two trials have been postponed, however, with the first one starting on March 13, 2017 from its original date of February 6, 2017. The other trial has also been delayed to April 24, 2017 from its March 13, 2017 date.
Xarelto also has controversy surrounding it due to false claims in advertising. The FDA said that advertisement about it is false or misleading since it has not noted the risk associated with its use. Use of Xarelto could lead to internal bleeding and there is no medical method said to reverse this effect.
Internationally, Xarelto is manufactured by Bayer A.G. while in the U.S. it is made by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson. Chemically, Xarelto is known as rivaroxaban. Both companies are faced with 7,200 lawsuits in the U.S., including the two mentioned lawsuits.
In other news, a breakthrough in the fight against Alzheimer's disease might have been reached with a new gene treatment being developed.
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Countering Xarelto critics, FDA backs clot-buster's benefits despite study's faulty device
Oct 11, 2016 | FiercePharma
By Carly Helfand
Johnson & Johnson and Bayer can breathe easy: The FDA declared Wednesday that a faulty device didn't distort the results of a key Xarelto trial.
In the wake of questions about Xarelto's crucial atrial fibrillation trial, the agency said it’s “quite likely” that the later-recalled monitoring device prompted higher-than-usual doses of the old-guard therapy warfarin in the trial. That's the treatment Xarelto topped in the Phase III study, ROCKET AF.
But the increased doses “were likely to have [a] quite modest” effect on clinical results, the agency said. It's “very unlikely” that, if the device had been up to snuff, Xarelto’s risk/benefit profile--compared with warfarin’s--would have come out looking much different, the regulators wrote.
The FDA isn’t the first regulatory agency to come to that conclusion. After launching its own probe last December, the European Medicines Agency in February said the now-recalled Alere device hadn’t distorted ROCKET’s main findings, which established Xarelto’s superiority over warfarin.
Meanwhile, it’s great news for the two companies, both of which count on big sales from the standout med. Bayer, for one, recently hiked peak sales estimates for the drug, taking the company's forecast to more than €5 billion from €3.5 billion.
But they’re not totally in the clear. In September, an investigation by the BMJ faulted the pair for knowing about device-related concerns while the trial was ongoing--and failing to notify trial monitors or regulators about it.
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FDA Lifts Cloud Over J&J’s Xarelto With ROCKET-AF Re-Analysis
Oct 11, 2016 | Pink Sheet
By Sue Sutter
An FDA re-analysis of the ROCKET-AF trial of Janssen Pharmaceutical Cos.’s Xarelto (rivaroxaban) appears to close the books on the troubled, Robert Califf-led study by recommending against any labeling changes for the anticoagulant.
On Oct. 11, FDA announced the Division of Cardiovascular and Renal Products had reaffirmed the safety and efficacy of rivaroxaban as an alternative to warfarin in atrial fibrillation patients after completing a variety of analyses to assess the impact of a faulty coagulation monitoring device used in ROCKET-AF.
The 14,000-patient study served as the basis for the Factor Xa inhibitor’s November 2011 approval for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. (Also see "Xarelto Approval For Stroke Prevention Sets Up Marketing Battle With Pradaxa" - Pink Sheet, 7 Nov, 2011.)
“The rationale for the recall raised the possibility that patients in the warfarin arm of ROCKET were over-anticoagulated as a result of use of the INRatio device,” Rose said.
Califf, a cardiologist and the agency’s current commissioner, was co-principal investigator of the trial while he was at Duke University. Califf played a prominent role in securing a positive advisory committee recommendation for the anticoagulant (Also see "J&J Saves Xarelto; But Faces tough Label" - Pink Sheet, 1 Oct, 2011.). In the process, he staunchly defended the trial’s design. (Also see "ROCKET AF’s Design Causes Headaches For XareltoSponsors" - Pink Sheet, 19 Sep, 2011.)Monitoring Device Recall
However, the trial’s results have been called into question over reliability issues with the point-of-care International Normalized Ratio (INR) monitoring device used in the study.
“In July 2016, the Alere INRatio device was recalled due to the potential to generate inaccurate results,” FDA said. “This device was used to monitor warfarin therapy in the control group of the ROCKET-AF clinical trial.”
In Sept. 26 memo, cardio-renal team leader Martin Rose said the agency received information from Janssen in September 2015 that the INRatio device used at all study sites to monitor INR and adjust warfarin dose in ROCKET had been subject to a Class 1 recall event involving a “voluntary correction” of its labeling in December 2014.
The recall was based on post-marketing information indicating that INR values reported by the device were lower than near-contemporaneous readings from a laboratory-based device in certain patient groups.
However, excessive anticoagulation in the warfarin arm might have reduced the rate of ischemic stroke, which also was a component of the primary endpoint. “This might have distorted the study efficacy results in the opposite direction, i.e., against rivaroxaban,” Rose said.
“The rationale for the recall raised the possibility that patients in the warfarin arm of ROCKET were over-anticoagulated as a result of use of the INRatio device, potentially distorting the results of the study by increasing the rate of bleeding in the warfarin arm,” Rose said.
“This might include an increased rate of hemorrhagic stroke, a component of the primary efficacy endpoint,” Rose said. “These distortions would tend to bias the results in favor of rivaroxaban in comparisons of bleeding rates vs. warfarin, and possibly also bias the primary endpoint in favor of rivaroxaban.”
However, excessive anticoagulation in the warfarin arm might have reduced the rate of ischemic stroke, which also was a component of the primary endpoint. “This might have distorted the study efficacy results in the opposite direction, i.e., against rivaroxaban,” Rose said.
FDA and Janssen performed a variety of analyses to characterize the impact of the INRatio device on the ROCKET efficacy and safety results.
Most of the analyses involved data from a large pharmacokinetic/pharmacodynamic substudy embedded in ROCKET and that involved INR sampling at 12 and 24 weeks of treatment. About 87% of the 7,125 warfarin patients in the study had at least one pair of same-day INR samples that were run using the INRatio device at each patient’s study site (POC INR) and a lab-based device at Duke (LAB INR).
“The matched pairs of INR values enabled comparative analyses by FDA and Janssen of the performance of the two devices, and also analyses of the effects of differences between POC INR and LAB INR on rates of important outcomes in ROCKET,” Rose said. “FDA and Janssen also built mathematical models of INR vs. outcomes that generated expected bleeding and ischemic stroke rates in the two study arms and rivaroxaban vs. warfarin comparisons for these endpoints.”More Intensive Anticoagulation Had ‘Modest’ Effects
It is likely patients in the warfarin arm received higher doses of warfarin than they would have if the INRatio device produced results similar to those of the lab-based device at Duke, FDA concluded.
“However, the effects of this increased intensity of anticoagulation on clinical outcomes were likely to have been quite modest,” Rose said.
Estimated reductions in the rates of bleeding events with warfarin were small enough that rivaroxaban’s benefits would still outweigh its risks, the review found. In addition, two of the analyses predicted that the ischemic stroke rate would be increased in the warfarin arm, which would have resulted in improved efficacy for rivaroxaban relative to warfarin.
“It seems very unlikely that if the device had performed similarly to the INR assessment device at Duke, the benefit/risk profile of rivaroxaban compared to warfarin would have been notably different from the profile based on the observed results of ROCKET,” Rose said. “Accordingly, the conclusion we made in 2011 that the benefits of rivaroxaban in patients with non-valvular atrial fibrillation outweigh its risks should not be changed.”Labeling Untouched
Rose further concluded that no labeling changes were warranted to reflect the impact of the INRatio device’s use in ROCKET.
“No other major regulatory action should be taken with respect to rivaroxaban,” Rose said. “Our conclusions regarding the issues addressed by this review should be communicated to the public in a suitable manner, but not through any changes in labeling.”
FDA said Califf, who joined the agency in February 2015 and took the helm a year later, was not involved in the agency’s re-analysis of the ROCKET data.
“Dr. Califf was recused from the matter,” an agency spokeswoman said. “We have no comment beyond what is in the posted materials.”
The European Medicines Agency reached a similar conclusion affirming the results from the ROCKET-AF trial in February. (Also see "Bayer's Xarelto 'Safe' Despite ROCKET Device Defect" - Scrip, 8 Feb, 2016.)
Janssen markets the drug in the US under an agreement with Bayer AG. "We’re pleased to see that the FDA’s reanalysis of the ROCKET-AF trial data confirms that the benefit-risk profile of Xarelto remains positive for reducing the risk of stroke in patients with non-valvular atrial fibrillation," Janssen said. "This conclusion comes directly after, and is in line with, the European Medicines Agency’s (EMA) recent review, which confirmed their original assessment, and with the independent reanalysis published in the New England Journal of Medicine.
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FDA Says Faulty Device Didn't Affect Xarelto Trial Results
Oct 11, 2016 | Law360
By Shayna Possess
Blood thinner Xarelto is a safe and effective treatment for patients with a type of irregular heartbeat called atrial fibrillation despite recent concerns regarding the clinical trial that was key to securing the medication’s approval, the U.S. Food and Drug Administration said Tuesday.
Xarelto, marketed in the United States by Johnson & Johnson unit Janssen Pharmaceuticals Inc. and outside the country by Bayer AG, scored FDA approval in November 2011 for reducing the rates of stroke and blood clots in people with atrial fibrillation. The disorder is a quivering or irregular heartbeat that doubles the risk of heart-related deaths and increases stroke risk fivefold if left untreated, according to the American Heart Association.
But the July recall of a monitoring device used in the clinical trial of more than 14,000 people that provided the primary data to support the agency’s blessing raised doubts. In response, the agency said Tuesday, it conducted a variety of analyses to determine the impact of Alere Inc.’s INRatio anti-coagulation monitoring device on the study results, concluding that, “effects on strokes or bleeding, including bleeding in the head, were minimal.”
The FDA first approved Xarelto in July 2011 for reducing the risk of blood clots, deep vein thrombosis and pulmonary embolism after knee or hip replacement surgery. But J&J and Bayer sought further approval for use with patients with nonvalvular atrial fibrillation and won it in November 2011, drawing on data from a clinical trial called Rocket-AF.
The trial enrolled thousands of patients to compare the efficacy of rivaroxaban, the generic name for Xarelto, to popular anticoagulant warfarin for reducing strokes in patients with atrial fibrillation, according to the agency.
Warfarin dosage has to be adjusted based on the observed international normalized ratio, a measure of the clotting tendency of a patient’s blood, according to one of the agency’s analyses. If the ratio is too high, blood can’t clot and potentially fatal bleeding events occur more frequently, but if the measure is too low, blood clots too quickly and ischemic strokes will happen more often, the analysis explained.
In the Rocket trial, INRatio was used to monitor warfarin therapy in the control group, raising concerns when the device was voluntarily recalled in July based on the potential to generate inaccurate results, according to the FDA. As a result, there were concerns that patients might have received more warfarin than they would have if the readings had been accurate, which could increase their bleeding rate and make Xarelto seem safer by comparison, according to the analyses.
The FDA determined, however, that the faulty device likely didn’t have substantial effects on the Rocket trial’s results, concluding that Xarelto is still a safe and effective alternative to warfarin in patients with atrial fibrillation.
Xarelto has also been the subject of numerous consumer suits, leading the U.S. Judicial Panel on Multidistrict Litigation to consolidate a slew in Louisiana federal court in December 2014. The panel concluded that plaintiffs posed common factual issues, including whether the drug's label sufficiently warned about its alleged risk of severe bleeding, as well as issues surrounding certain clinical trial results.
Four bellwether trials have been slated for 2017, according to court filings.
The Philadelphia County Court of Common Pleas also consolidated a number of product liability cases over the drug in January 2015 under a mass tort program. -
FDA: ROCKET AF Results Not Affected by Faulty INR Testing in Warfarin Arm
Oct 11, 2016 | TCTMD
By Michael O'Riordan
The US Food and Drug Administration (FDA) has concluded that inaccurate results from the point-of-care device used to measure international normalized ratio (INR) values in warfarin-treated patients as part of the ROCKET AF clinical trial did not materially affect the study’s findings.
The FDA’s Center for Drug Evaluation and Research (CDER), which today published the results of the latest review of data from the ROCKET AF clinical trial, states that while “it is quite likely” that patients treated with warfarin in the clinical trial received unintentionally higher doses of the anticoagulant, “the effects of this increased intensity of anticoagulation on clinical outcomes were likely to be quite modest.”
European regulators, conducting a similar review, reached similar conclusions last February.
First presented in 2010, ROCKET AF, a randomized clinical trial testing rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals) in patients with nonvalvular atrial fibrillation, showed the factor Xa inhibitor was noninferior to warfarin for preventing stroke or systemic embolism without increasing the risk of major or clinically relevant bleeding.
The results of the study have come under fire, however, mainly because of concerns about what went on with INR testing in the warfarin arm of the randomized trial. As reported by TCTMD, the study investigators have performed multiple analyses of the trial, including one in February 2016 and another in July 2016, given fears the INR values might have distorted the study’s findings.
The devices in question—the INRatio and the INRatio2 PT/INR Monitor System (Alere)—were voluntarily withdrawn from the US market this summer after discussions between the FDA and Alere. Issues with INRatio were raised as early as early as 2005, according to one report, but mainly gained traction in late 2014 when Alere issued a medical device correction—through a class I FDA recall notice—warning that the devices should not be used in patients with certain conditions because of the possibility INR results would be lower than expected with laboratory testing.
This raised the possibility that patients in the warfarin arm of ROCKET AF might have been overanticoagulated and led to an excess of bleeding events in the warfarin arm, including an increase in hemorrhagic stroke, which was a component of the primary endpoint. “These distortions would tend to bias the results in favor of rivaroxaban in comparisons of bleeding rates versus warfarin, and possibly also bias the primary endpoint in favor of rivaroxaban,” according to CDER reviewers.
Running the INR Results Against Lab-Based Testing
In a review of 7,125 warfarin-treated patients who had same-day samples tested using the point-of-care INR device and a laboratory-based device at Duke University, the FDA found the INR values were, on average, 13% lower than when tested in the laboratory. Other analyses also assessed the risk of bleeding in patients with varying degrees of discordancy based on the point-of-care and laboratory INR values. The agency then performed mathematical modeling to estimate clinical outcomes that might have occurred had ROCKET AF used a more accurate INR assay to guide warfarin dosing.
The analyses predicted a small decrease in the expected rate of major bleeding in the warfarin-treated patients compared with the actual rate of 3.45 events per 100 patient-years in the trial. Using different models, the reduction ranged anywhere from 7% to 10% of the observed rate. “Overall, these estimated reductions in the rates of bleeding events in the warfarin arm were small enough so that the benefits of rivaroxaban would still outweigh its risks if efficacy were not affected,” the CDER report says.
Based on their review, the FDA believes that if the INR devices had performed as well as the laboratory-based assessments, it is unlikely that the “benefit/risk profile of rivaroxaban compared to warfarin would have been notably different from the profile based on the observed results of ROCKET AF.” Given that, there is no need to change the label to reflect the impact of the INRatio device in the trial, and no other regulatory action is needed, says the FDA.
Two weeks ago, the controversy surrounding the INR values took yet another twist when the BMJ reported that, because of concerns about inaccurate reading, Janssen initiated a safety program shortly after the ROCKET AF trial began. The journal stated that Janssen did not reveal the results of their program—known as the Covance recheck program—to the trial’s data and safety monitoring board, Bayer, or the FDA before rivaroxaban was approved in 2011. Janssen denied the “central premise” of the journal’s report.
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FDA Reaffirms Safety And Efficacy Of Rivaroxaban
Oct 11, 2016 | CardioBrief
By Larry Husten
Following a year of controversy and uncertainty relating to the anticoagulant drug rivaroxaban (Xarelto, Johnson & Johnson), the FDA has reaffirmed the drug’s safety and efficacy.
Rivaroxaban is approved for stroke reduction in patients with atrial fibrillation. The indication is based on results of the ROCKET-AF trial, which compared rivaroxaban to warfarin. New questions about the trial emerged last year when it became known that the portable device used to adjust warfarin usage in the trial had been recalled due to unreliability in some patient populations.
On Tuesday the FDA said that it had concluded “that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation.” The review statement echoes previous reviews from the European Medicines Authority, Johnson & Johnson (and its partner, Bayer), and the ROCKET AF investigators.
The FDA conducted three separate reviews (clinical, statistical, and clinical pharmacology) of the problem. The FDA concluded that the point of care device in the trial produced INR values that averaged 13% lower than laboratory INR values obtained from stored samples during the trial. The FDA concluded that the “estimated reductions in the rates of bleeding events in the warfarin arm were small enough so that the benefits of rivaroxaban would still outweigh its risks if efficacy were not affected.” This finding was “directionally consistent” with the earlier studies.
The clinical reviewers said there was no need to change the rivaroxaban label and that “no other major regulatory action” needed to be taken.
Asked to comment on the FDA statement, Sanjay Kaul(Cedars Sinai) said that “the results of the FDA analysis are aligned with those conducted by the EMA, sponsor and the Duke investigators. It is an inference I personally concur with. I hope the BMJ investigative reporters and the skeptical external experts are satisfied by this report.”
But the BMJ investigator, Deborah Cohen, said she still has concerns about the drug and thinks that the “whole saga raises ethical issues” that still need to be addressed. Here is her full comment:
“I’m not totally convinced this is a clean bill of health. The FDA confirmed that the device malfunctioned. They confirmed that the malfunction resulted in warfarin patients experiencing additional bleeds – the modified event rate went down. Finally, the FDA calculated that the hazard ratio for major bleeds could be as high as 1.16. (Up from 1.05 (CI: 0.91, 1.20) in ROCKET-AF).
“Although not the highest level of evidence, this finding seems to be supported in observational studies by the FDA (Graham et al).
“The FDA actually said the reason for no label change is because ‘we think that a labeling change to describe the modeling results would be very difficult to write in a concise manner…’
“But while the FDA might say that the benefit/harm ratio is acceptable, the whole saga raises ethical issues. Given Janssen knew that the device was malfunctioning – were trial participants put at unnecessary risk of major bleeds? And that surely is something that can’t be ignored.”
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FDA finds study data supporting Xarelto approval OK despite recalled Alere INRatio device
Oct 11, 2016 | Seeking Alpha
In a statement, the FDA reports that it has concluded that Johnson & Johnson's (JNJ -1.6%) blood thinner XARELTO (rivaroxaban) is a safe and effective alternative to warfarin in patients with atrial fibrillation. The agency conducted a variety of analyses on a Phase 3 study, ROCKET-AF, that supported the company's marketing application and 2011 approval.
The FDA reexamined the data because Alere's (ALR -1.6%) INRatio device was used to monitor warfarin therapy in the control group. Alere recalled the device in July of this year due to the risk of inaccurate results.
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FDA sounds the all-clear for J&J blood thinner
Oct 13, 2016 | NJ.com
By Kathleen O'Brien
Johnson & Johnson's popular blood-thinning medication, Xarelto, is safe and effective despite earlier concerns about the research behind it, the U.S. Food and Drug Administration has ruled.
The drug had come under a cloud after the FDA recalled a device that was used to measure the effectiveness of blood thinners in Xarelto's clinical trial. That trial showed the J&J drug to be better at preventing ischemic attacks than the more commonly prescibed drug, warfarin.
The device's recall raised the possibility that research result was so flawed it was invalid.
However, the FDA announced earlier this week that its analysis of the faulty device's measurements indicated little impact on the validity of the clinical trial's outcome.
"The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation," the agency stated.
Both drugs are used to prevent strokes in patients with atrial fibrillation.
Xarelto is sold by Janssen Pharmaceutical Companies, a division of Johnson & Johnson.
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FDA reaffirms anticoagulant drug rivaroxaban’s safety and efficacy
Oct 12, 2016 | News Tonight Africa
By Kehumile Mazibuko
Following an extended trial and uncertainty, the U.S. Food & Drug Administration (FDA) on Tuesday reaffirmed the anticoagulant drug rivaroxaban’s safety and efficacy.
Rivaroxaban has been approved for reducing odds of stroke in patients with atrial fibrillation. The federal agency reaffirmed the drug’s safety and efficacy after the ROCKET-AF trial, which compared the controversial drug to warfarin.
The drug trigged safety concerns last year when it was learnt that the portable device used to adjust warfarin usage had been recalled because of unreliability in some patients. A subsequent probe by BMJ suggested that Johnson & Johnson (J&J) was aware of the issue and looked into it without informing relevant regulatory bodies.
While the FDA reaffirmed the drug’s safety and efficacy, BMJ investigator Deborah Cohen argued that she still has concerns about its use.
Cohen said in a statement, “I’m not totally convinced this is a clean bill of health. The FDA confirmed that the device malfunctioned. They confirmed that the malfunction resulted in warfarin patients experiencing additional bleeds -- the modified event rate went down.”
However, the FDA claims that it reaffirmed the drug’s safety after conducting three separate reviews. It concluded that the estimated decreases in the rates of bleeding events in the warfarin arm were quite enough and the drug’s benefits outweighed its risks. The finding was directionally consistent with the pervious reviews.
Read more: http://newstonight.co.za/content/fda-reaffirms-anticoagulant-drug-rivaroxaban-s-safety-and-efficacy#ixzz4Mtg2i011
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