FDA Approves Zilver PTX Drug-Eluting Stent For Peripheral Arterial Disease Reply

The FDA today approved Cook Medical’s Zilver PTX stent. It is the first drug-eluting stent (DES) approved for the treatment of peripheral arterial disease (PAD) in the superficial femoral and proximal (i.e., above the knee) popliteal artery. The new stent will provide a new treatment option for treating patients with PAD. Current treatments include exercise, drug therapy, balloon angioplasty, bare-metal stents, and surgical bypass.

“The clinical study demonstrated that the Zilver is more effective than balloon angioplasty for the treatment of symptomatic peripheral artery disease in above-the-knee femoropopliteal artery,” said Christy Foreman, of the FDA’s Center for Devices and Radiological Health, in an FDA press release. “This approval expands the treatment options for patients suffering from symptomatic peripheral artery disease to include the Cook Zilver PTX drug eluting stent.”

The FDA said the Zilver PTX stent is contraindicated in people with “stenoses that cannot be dilated to permit passage of the catheter or proper placement of the stent, patients who cannot receive recommended drug therapy due to bleeding disorders, or women who are pregnant, breastfeeding, or plan to become pregnant in the next five years.” In clinical studies the most common major adverse event associated with the stent was restenosis requiring treatment to restore patency.

The FDA is requiring Cook Medical to perform a five-year post-approval study of 900 patients.

“This approval marks the start of Cook’s program to bring the benefits of drug elution to U.S. physicians treating the peripheral arteries,” said a Cook Medical executive, Rob Lyles. He said that Cook Medical intends by the end of 2013 to offer a “full suite of drug-eluting peripheral stents in the most commonly used lengths and diameters.” The Zilver PTX will be initially available in an 80 mm length in 6 mm and 7 mm diameters. The company has also received approval to market 40 and 60 mm length stents, though these will not be available until early 2013. Cook said that it expects to receive FDA approval for a 120 mm length stent next year.
Click here to read the FDA and Cook Medical press releases…

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TAVI: Belgian Researchers Slam Evidence Base And Overuse In Europe 1

The growing and enthusiastic adoption of transcatheter aortic valve implantation (TAVI) in Europe has no justification, according to three researchers who performed a health technology assessment for the Belgian government. In a paper published in BMJ, the authors from the Belgian Health Care Knowledge Centre conclude that TAVI should only be used in patients “who are deemed inoperable for technical reasons,”  which is about 10% of patients “of those currently considered for treatment.”

In their paper the writers do not identify any new concerns about TAVI, but they weave together the various threads of criticism that have been directed at the dissemination of TAVI. Hans Van Brabandt, Mattias Neyt, and Frank Hulstaert also charge that the evidence base for TAVI is deeply flawed as a result of an unpublished negative trial, serious baseline imbalances between controls and TAVI patients in the PARTNER trial, and unreported conflicts of interest by the principal investigator of PARTNER.

By the end of 2011 approximately 40,000 TAVI procedures had been performed, they write. Nearly all of the procedures were performed in Europe, where devices do not undergo the same regulatory scrutiny as drugs, needing only a CE mark to go on the market, “putting them on the same footing as domestic appliances such as toasters.” They note that TAVI was used in Europe for four years before the FDA approved its use in the US, but only for patients who were not surgical candidates and only when the transfemoral approach was used.

Despite the greater rigor of the US regulatory process, the authors write that after their careful review of all the available evidence “we remain far from convinced that it is adequate” and that “the arguments supporting the widespread use of TAVI do not stand up to scrutiny.”

Although in  the PARTNER A trial TAVI met the predefined criteria for non-inferiority when compared to surgery, the authors write that strokes, TIAs, and major vascular complications occurred more often with TAVI. TAVI performed better in the PARTNER B trial, which studied patients who were not eligible for surgery, but TAVI was still associated with a higher rate of stroke and vascular events. Results of the two trials “suggest that TAVI can be justified for inoperable patients on clinical grounds,” but, write the authors, this conclusion is weakened because the FDA, Edwards (manufacturer of the Sapien TAVI device), and trial investigators have failed to provide data to the authors, despite repeated requests, about a follow-up study comparing TAVI to standard therapy in 90 patients. The failure to share the data, they write, “is both ethically and scientifically unacceptable and should be legally regulated in future.”

The authors also maintain that  the principal investigator of the PARTNER trial, Martin Leon, did not fully disclose his financial interest in TAVI. Although it was disclosed in the NEJM papers that Leon had received $6.9 million from Edwards when it purchased Percutaneous Valve Technologies, which Leon had co-founded, the articles did not mention that Leon “was to receive three further payments on the achievement of three milestones: successful treatment of 50 patients, regulatory approval in Europe, and limited approval in the US.”
Click to continue reading, including a comment from Sanjay Kaul…

FDA Approves A New Weight Loss Drug, Breaking a 13 Year Drought Reply

The FDA announced today that it had approved its first new weight loss drug in 13 years. Lorcaserin, which will be sold under the brand name of Belviq, is manufactured by Arena Pharmaceuticals and will be distributed in the US by Eisai.

Lorcaserin is indicated for use in obese adults (BMI 30 or above) or overweight adults (BMI 27 or above) with a coexisting weight-related condition such as hypertension, diabetes, or high cholesterol.

“Obesity threatens the overall well being of patients and is a major public health concern,” said the FDA’s Janet Woodcock, in an FDA press release. “The approval of this drug, used responsibly in combination with a healthy diet and lifestyle, provides a treatment option for Americans who are obese or are overweight and have at least one weight-related comorbid condition.”

The FDA is requiring Arena to conduct six postmarketing studies, including a long-term CV outcomes trial. The label will note that the effect of lorcaserin on cardiovascular morbidity and mortality have not been established  and that its safety and efficacy when used with other weight loss drugs has not been tested.

Arena said that the FDA has recommended to the Drug Enforcement Administration (DEA) that lorcaserin be classified as a scheduled drug. The drug will not be available until after the DEA reviews the recommendation and decides whether the drug will be scheduled. During a press conference the company said that DEA scheduling normally takes from four to six months, indicating that the drug might not become available this year.

Click here to read press releases from the FDA and from Arena/Eisai…

FDA Once Again Delays Approval Of Apixaban (Eliquis) 2

The FDA has once again delayed approval of apixaban (Eliquis), the much-anticipated oral anticoagulant. Bristol-Myers Squibb and Pfizer announced today that it had received a a Complete Response Letter (CRL) to the New Drug Application (NDA) for the drug for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

The two companies reported that the FDA had asked for “additional information on data management and verification from the ARISTOTLE trial”  No new trials were requested by the FDA, according to the companies, who said they “will work closely with the FDA on the appropriate next steps” for the NDA.

Following the widely praised publication and presentation of ARISTOTLE, it was widely anticipated that apixaban would sail through the FDA approval process. This view gained early confirmation when the FDA granted priority review for the NDA last November, but the picture grew cloudier earlier this year when the FDA extended the action date by three months.

Wall Street analyst Tim Anderson speculated that apixaban might still gain FDA approval in 2012, though firm predictions are difficult since Bristol-Myers Squibb and Pfizer have not released details about the questions raised by the FDA in the CRL.

Click here to read the press release from Bristol-Myers Squibb and Pfizer

Decision on Apixaban (Eliquis) Pushed Back By Three Months 1

Update, March 1, 5 PM: Ramsay Baghadi of the RPM Report says that the Cardiorenal committee will take up the apixaban NDA on Mary 22 and the rivaroxaban supplemental NDA for the ACS indication on May 23, but this information has not been confirmed.

Confirming earlier speculation by a Wall Street analyst, Pfizer and Bristol-Myers Squibb announced on Wednesday evening that the FDA had extended by three months the action date for the new drug application (NDA) for the highly anticipated oral anticoagulant Eliquis (apixaban). The application is for their important indication of stroke prevention in atrial fibrillation. The FDA had previously granted the application a 6-month priority review, resulting in a March 28th decision date. The new decision date is June 28,2012.

Sanford Bernstein research analyst Tim Anderson first raised the idea that the decision date might be delayed back on February 10th. On Tuesday Anderson released another note with additional evidence for the delay, based on the release of the tentative FDA advisory committee calendar for 2012, suggesting that the apixaban NDA will be subject to an advisory panel meeting. According to the calendar, the Cardiovascular and Renal Drugs Advisory Committee is scheduled to meet on March 27 and May 23. The agenda for the March 27 session is already set for a discussion of Replagal for Fabry disease. Recall that yesterday the FDA granted a priority review to the NDA for rivaroxaban for ACS, resulting in a decision date of June 29. One might speculate then that another day might be added to the May 23rd meeting for consideration of the rivaroxaban and apixaban NDAs.

Anderson wonders why the FDA has suddenly put the brakes on the apixaban approval, which had heretofore seemed uncomplicated. He writes:

Our best guess remains that FDA may be seeking cover, given the safety experience following competing drug Pradaxa’s approval in 2010.  Additionally, FDA may be seeking advice on things like product labeling and what claims would be allowed.

We might also note that the approval of rivaroxaban was far more difficult than had been expected. Remember that the ROCKET AF trial had been presented and published with broad approval, but then came under heavy fire from FDA reviewers. It is possible that FDA reviewers may also raise previously unsuspected concerns about the pivotal apixaban trial, ARISTOTLE, though no serious criticisms have been publicly raised so far.
Click here to read the press release from Pfizer and Bristol-Myers Squibb…

FDA Advisory Panel Gives Green Light to Qnexa Diet Pill 2

Breaking a long streak of bad news for diet drugs, an FDA advisory panel on Wednesday voted 20-2 in favor of approval for Qnexa, the combination of  phentermine and topiramate under development by Vivus. Panel members strongly suggested that Vivus be required to perform a cardiovascular outcomes trial, though it was not immediately clear if this would have to be completed prior to approval.

Birth defects associated with Qnexa were another source of concern. The panel expressed strong support for a risk evaluation and mitigation strategy (REMS) to accompany any approval. But the panel ultimately was impressed by data showing a 10% weight loss at two years for people taking the drug.

“Of all the obesity drugs, this one has the highest efficacy in terms of weight loss, so that shifts the balance in terms of requiring a post-approval study rather than a pre- approval study,” panel member Sanjay Kaul told Bloomberg News.

Kaul told CardioBrief that the 20-2 vote appears more enthusiastic than the actual sentiment of the panel. Panel members remain concerned about the uncertainty regarding cardiovascular risk of the drug, including the possible adverse effects on blood pressure and heart rate. Kaul said the panel was impressed by the company’s proposed REMS, but that there is little evidence demonstrating that even a strong REMS can significantly reduce adverse outcomes like birth defects.

Two other diet drugs, Contrave, the combination of naltrexone and bupropion, from Orexigen, and locaserin, from Arena, have been struggling to gain FDA approval in recent years. No new diet drug has been approved for marketing in the United States since 1999.

FDA Approves Medtronic’s Resolute Drug-Eluting Stent for Treatment of CAD, Including Diabetics Reply

The FDA has approved the Medtronic Resolute zotarolimus-eluting stent for the treatment of coronary artery disease. The Resolute DES is approved for use in a wide variety of patients, including diabetics. The new stent uses the same drug-and-polymer combination as the popular Resolute Integrity DES. The Resolute clinical trial program enrolled more than 5,000 patients worldwide, a third of whom had diabetes.

“The Resolute Integrity DES offers several notable benefits, starting with outstanding deliverability, which means it’s exceptionally easy to navigate the stent on the delivery system through the coronary vasculature to the narrowed arterial segment that requires treatment,” said Martin B. Leon, a principal investigator of the RESOLUTE US clinical study, in a Medtronic press release. “Its approval by the FDA is based on the impressive performance of the Resolute DES in a wide variety of patients. With the device’s compelling combination of deliverability, efficacy and safety, not to mention that it is the first DES approved for patients with diabetes, the Resolute Integrity DES promises to gain rapid acceptance in cath labs nationwide.”
Click here to read the Medtronic press release…