J&J's Ethicon recalls blood-stopping hemostat; FDA warns of deadly risk

Johnson & Johnson unit Ethicon is recalling its some of Surgiflo hemostatic kits, warning that a packing issue could lead to breaches in the product, and the FDA has assigned its most serious label to the recall.

Surgiflo is a topical, absorbable hemostat used to stop bleeding in surgical procedures. Ethicon became aware of the packing problem back in the spring and is urging customers to return the affected lots once they're identified. The FDA has branded the affair a Class I recall, saying the recalled products could be rendered non-sterile and their use could to lead to serious injury or death.

Ethicon says it is yet to receive any reports of adverse events from Surgiflo, but the FDA is asking customers to report any problems through its online MedWatch system.

Ethicon has a long history of regulatory dustups, including the costly and deadly vaginal mesh debacle and an October Class I over malfunctioning surgical staplers. However, the company last week won FDA approval for its Evarrest Fibrin Sealant Patch, and J&J has committed to spending $185 million to expand Ethicon's suture-making plant in Athens, GA.

- Here's the FDA's notice

The Medicines Company and Bristol-Myers Squibb Agree to Global Alliance For Recothrom

The Medicines Company builds on portfolio and capabilities in acute and intensive care hospital medicine with marketed perioperative biologic

Parsippany, NJ, and Princeton, NJ, USA I December 12, 2012 I The Medicines Company (NASDAQ:MDCO) and Bristol-Myers Squibb Company (NYSE: BMY) announced today that the companies have signed a global license and two year collaboration for Recothrom®, a recombinant thrombin approved by the U.S. Food and Drug Administration for use as a topical hemostat to control non-arterial bleeding during surgical procedures.

Clive Meanwell, M.D., Ph.D., Chairman and CEO of The Medicines Company said, “As a marketed, growing product to control blood loss in the hospital, we believe Recothrom is a strategic fit that enables operating leverage with The Medicines Company’s emerging perioperative care portfolio. The financial structures and net revenues fit well with our strategy for aggressive and sustainable growth in acute and intensive care medicine. Of course, thrombin is also a hemodynamic target we know well based on our experience with Angiomax® (bivalirudin), a thrombin inhibitor.”

“The Medicines Company’s expertise in advancing the treatment of critical care patients in hospital settings worldwide makes it the natural partner to bring Recothrom to patients and physicians,” said Giovanni Caforio, President, U.S. Pharmaceuticals of Bristol-Myers Squibb. “This agreement is part of Bristol-Myers Squibb’s ongoing efforts to simplify operations, improve our efficiency and better position ourselves to focus on our important work in areas of significant unmet medical need that are critical to our long-term success."

Recothrom net revenues in 2011 were $65 million. The product is currently commercially available in the United States and Canada. The intellectual property license agreement is global and The Medicines Company anticipates pursuing approvals in additional countries.

The transaction is expected to be accretive to earnings per share (EPS) for The Medicines Company in 2013.

Under terms of the agreement, The Medicines Company will pay Bristol-Myers Squibb an upfront collaboration payment of $105 million and an upfront option fee of $10 million. The Medicines Company has also agreed to pay Bristol-Myers Squibb a tiered royalty on annual net revenues of Recothrom during the two-year collaboration term. Bristol-Myers Squibb will retain responsibility for the manufacturing of Recothrom and will be The Medicine Company’s exclusive supplier of Recothrom during the term of the agreement. The option enables The Medicines Company to acquire the Recothrom assets for a purchase price based on average net sales during the two-year collaboration term.

The transaction is expected to be minimally accretive to EPS for Bristol-Myers Squibb in 2013 and 2014.

The transaction is subject to the satisfaction or waiver of closing conditions, including the expiration or termination of applicable waiting periods under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, and the delivery by Bristol-Myers Squibb of certain audited financial information relating to the business.

European Medicines Agency Updates Advice for Spraying Fibrin Sealants During Surgery

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued new instructions to promote safe use of the fibrin sealants Tisseel, Tissucol, Artiss, and Beriplast P during surgery. This advice follows that issued for two other fibrin sealants, Evicel and Quixil, in November 2012. Employed to help reduce local bleeding, these sealants are typically dripped or sprayed onto bleeding tissue to form a fibrin clot.

Reports of gas embolism with Evicel and Quixil in association with the use of spray devices that use a pressure regulator prompted a review of fibrin sealants. These events appear to be related to the use of the spray device at higher-than-recommended pressures and/or in closer-than-recommended proximity to the tissue surface, EMA stated in a press release.

Although EMA reports that risk of gas embolism with Tisseel, Tissucol, and Artiss when applied as spray during surgery was considered to be very low, the Committee concluded that the risk cannot be excluded. It urges that product information for these medicines be updated with new instructions to optimise their safe use. EMA stated the following: 

• The product information should be updated with clear and consistent advice for healthcare professionals regarding recommended pressure and distance to use during spraying application.
• The marketing-authorisation holders for these medicines should ensure that they are used with pressure regulators that do not exceed the maximum pressure required to deliver the fibrin sealant, and that they contain labels stating the recommended pressure and distance.
• The product information should include a warning that the risk of gas embolism appears to be higher when fibrin sealants are sprayed using air, as compared to CO2, and patients should be closely monitored for signs of gas embolism.
• Healthcare professionals in the European Union (EU) will receive a letter outlining the updated information on the safe use of these medicines.

For the fibrin sealant Beriplast P (and associated names), however, the CHMP concluded that "there is no risk associated with this product because it does not require a gas-assisted spray device during application, therefore there is no risk of gas embolism with this product when used in accordance with prescribing advice and with the recommended device."

Omrix, a Johnson & Johnson unit, obtains FDA approval for fibrin sealant

Johnson & Johnson (NYSE: JNJ) unit Omrix Biopharmaceuticals Ltd. has obtained US Food and Drug Administration (FDA) approval for its fibrin human sealant patch, one of Omrix's most interest products and the reason why Johnson and Johnson acquired it for $438 million in 2007.

The product, now called Evarrest, is based on Omrix's biological sealant for stopping problematic bleeding during surgery. "Unexpected and uncontrollable bleeding during surgery poses a significant challenge to surgeons, and in some surgical procedures can raise the patient's mortality rate to 20%," says Ethicon Biosurgery (the J&J division which includes Omrix) in its press release.

Omrix's biological sealant is currently used to stop bleeding during surgery or from wounds, but the Evarrest patch Evarrest is easier to use. To stop bleeding, the surgeon places the sealant over the wound and manually compresses it in place for three minutes. The sealant becomes part of the body, gradually degrading over several days or weeks.

The sealant is based on the production of clotting substances in human blood plasma. Ethicon Biosurgery says, "Clinical studies demonstrate that Evarrest is 98% effective in stopping bleeding and maintaining hemostasis compared to the current standard of care at 53%, potentially minimizing disruption to the surgical procedure."

The FDA approval is good news for Johnson & Johnson and for Israel's life sciences industry, and the company will produce Evarrest in Israel, at least over the next few years.

Johnson & Johnson unit Ethicon Inc., which is responsible for hemostasis and sealing solutions to which Omrix belongs, is also considering other options for producing Evarrest and other products later on. It is in talks with Swiss's Octapharma AG, founded by Omrix founder Robert Taub, for this purpose. Omrix was a spin-off of Octapharma, a producer of human plasma products.

In 2009, the State of Israel sued Omrix's founders and Johnson & Johnson for not paying royalties on the acquisition of the intellectual property of the inventor of Omrix's products, a doctor at Sheba Medical Center Tel Hashomer. Omrix and Johnson & Johnson say Omrix was responsible for most of the invention, or that which it received it from Octapharma. The case is still pending, and while it has not yet affected Ormix's thriving operations in Israel to date, it may affect them in the future.