RECOTHROM Becomes the First and Only Topical Thrombin Indicated for Use in Children Greater Than or Equal to One Month of Age

PARSIPPANY, NJ--(Marketwired - May 9, 2013) -  The Medicines Company (NASDAQ: MDCO) today announced that the U.S. Food and Drug Administration (FDA) has expanded the indication for RECOTHROM®, Thrombin topical (Recombinant) to include use in pediatric patients, following completion of a post-approval pediatric clinical trial commitment. RECOTHROM is a recombinant topical thrombin now indicated to aid hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature, or cautery) is ineffective or impractical in adult and pediatric populations greater than or equal to one month of age. RECOTHROM provides patients greater than one month of age an alternative to bovine or human plasma derived thrombin. 

"Pediatric patients, in various surgical settings, have an increased chance of repeat surgeries. RECOTHROM has been studied in pediatric patients and shown to have a low rate of immunogenicity, and offers an important tool for use in this patient population," said Kevin N. Foster, MD, MBA, FACS, Chief, Burn Services, The Arizona Burn Center at Maricopa Medical Center.

The recent FDA approval is based, in part, on data from a completed Phase 4, open-label, single-group safety and immunogenicity study. This study was conducted in 30 pediatric patients greater than one month of age undergoing synchronous burn wound excision and skin grafting. The safety of RECOTHROM in pediatric patients greater than or equal to one month of age is supported by these data and by extrapolation of efficacy from adequate and well-controlled studies of RECOTHROM in adults. Safety and efficacy has not been established in neonates.

"Our purpose is to save lives, alleviate suffering and improve the economic efficiency of the approximately 2,500 leading hospitals in the world," said Brent Furse, Senior Vice President and Chief Customer Officer of The Medicines Company. "There are several hundred leading hospitals in the United States that conduct thousands of surgical procedures in pediatric patients each year. We believe the expanded pediatric indication for RECOTHROM provides an opportunity to make this topical hemostat available to a broader range of surgical patients."

About The Medicines CompanyThe Medicines Company (NASDAQ: MDCO) provides medical solutions to improve health outcomes for patients in acute and intensive care hospitals worldwide. These solutions comprise medicines and knowledge that directly impact the survival and well-being of critically ill patients. The Medicines Company's website is www.themedicinescompany.com.

King Pharma Disappoints

King Pharma's branded Pharmaceuticals segment declined 43.3% with revenues coming in at $160.8 million. Revenues of almost all key products declined from the year-ago period.
Thrombin-JMI sales declined 25.9% to $32.2 million. We expect Thrombin-JMI sales to continue declining due to tough competition in the form of Bristol-Myers Squibbs’ Recothrom and Johnson & Johnson’s Evithrom.

Pathogen Safety of Evithrom

Omrix Q3

Robert Taub
Thank you, Asaf. As Asaf mentioned, this quarter was another record quarter for biosurgery product sales – $9.5 million. Evicel is continuing to be a strong performer. The number of total accounts continues to increase steadily, and in quarter three, end user sales by our partner, Ethicon, once again included a very significant amount of repeat business. By year-end, we believe that total sales of Evicel will be approximately the same as our competitor.
Additionally, as mentioned in a recent press release, we announced that the EMEA approved Evicel in Europe. Evicel is now licensed for marketing in 27 plus three countries – the 27 countries of the European Union plus another three in Europe, and Ethicon will begin to sell Evicel on a country-by-country basis as Quixil is gradually phased out.
Next, Evithrom, our human-based thrombin standalone product continues to experience moderate dollar sales growth in this market. In quarter three, the total number of accounts purchasing Evithrom, however, increased by 50%, with new customers comprising 52%. As you're probably aware, however, there is currently fierce price competition in the thrombin standalone market, and as we have predicted, the market is moving toward thrombin enhanced hemostats, and we are currently developing two such products.
I would now like to update you on our Fibrin Pad. As you may recall, we have two trials, one in the U.S. in mild-to-moderate bleeding and a second one in Israel in severe bleeding.
With respect to the U.S. trial, we completed enrollment of the 90 patients needed to conduct interim analysis. We were pleased to report that the analysis showed superiority of the Fibrin Pad over Surgicel. Having demonstrated superiority, we are now able to continue with open-label enrollment. The trial will continue to enroll patients only to the Fibrin Pad arm, and according to the study design, we are required to treat at least 100 total patients for safety, which means another additional 40 patients with the Fibrin Pad.
Shortly after we announced that we had achieved superiority we were informed that the U.S. Phase II study had been suspended after a patient had experienced postoperative bleeding. This patient was not among the first 90 enrolled, but part of the subsequent 40 already. Many of you have asked why the trial was suspended if rebleeding is an expected event in surgery and in this protocol. The reason is simple. The protocol is written so that if there is a case of postoperative bleeding the trial must be suspended and an investigation must be conducted. Therefore, the decision to suspend the trial was an administrative one.
A Data Safety Monitoring Board, or DSMB, conducts the investigation and then provides a recommendation on how the trial is to proceed or if it is to be modified or even discontinued. We have now reported that the DSMB concluded their investigation and recommended that the clinical trial resume without any modifications, which it did.
I want to clarify that the DSMB's role is not to determine the relationship between the adverse event and the product. We, however, conducted a thorough product investigation and concluded that there is no issue with the clinical material.
I would still like to emphasize that a trial continuation with no modification is the absolute best case outcome. Therefore, we remain on target to complete enrollment of the 130 patients by the end of '08 or early '09. Although we still expect to be within the window of prior timeline guidance, due to the two-week investigation we are now more comfortable with an early '09 time frame. Once we complete the two-month follow-up and finish analyzing the data, we expect to file the BLA with the FDA in the first half of '09 and then assuming a standard 10-month review, we expect the approval in the first half of 2010.
Now, regarding the severe bleeding indication, I am pleased to inform you that we now have the approval from the British MHRA on behalf of the European Union to conduct a study in soft tissue severe bleeding.
I draw your attention to the fact that the indication and protocol are quite similar to the mild-to-moderate study which is ongoing in the United States. This EU severe bleeding study will be a pivotal study leading to an indication for the use of the Fibrin Pad in severe bleeding in soft tissue surgery. This kind of bleeding is different from the target bleeding in the exploratory Phase II study which we started some time ago in Israel.
Indeed, the Israeli study was purposefully designed to be the most challenging as it addresses the control of severe bleeding when the product is applied directly onto the resected solid organ, such as a kidney, a prostate, a liver or highly vascularized organs, and these organs are not soft tissues.
As you know, we reported a postoperative bleeding event in the Israeli trial. We are conducting an investigation, and pending the conclusion of the investigation of the rebleeding case we have decided to discontinue enrollment of additional patients in that Israeli trial and are focusing on initiating the European trial. But you should understand that the clinical development plan of the Fibrin Pad is proceeding well with a mild-to-moderate study in the United States and a severe bleeding study which will be initiated in Europe in the first half of '09.
Let me give you some details on the European study design. As I mentioned, it is a pivotal clinical study evaluating the safety and efficacy of our Fibrin Pad in soft tissue severe bleeding in abdominal, pelvic, retroperitoneal and noncardiac thoracic surgery. The study is a randomized multicenter clinical study evaluating the superiority of Fibrin Pad versus the standard treatment in controlling challenging severe bleeding in soft tissue for which standard methods of achieving hemostasis are ineffective or impractical.
Alright. Now, moving on to our passive immunotherapy business. Immunotherapy product and byproduct sales amounted to $10.1 million in the third quarter of 2008. And regarding our Phase III clinical trial in the United States for IVIG, the trial is proceeding according to expectations, and we are on track to file the BLA in the third quarter of 2009.
Erik Schneider – UBS
Okay. Great. Evithrom in the U.S., you previously said that it was – had higher sales than Zymo's Recothrom. Both are now in IMS. What is it – what's different about that channel that the IMS data show Evithrom with smaller dollars, but you're confident that they're actually larger?
Robert Taub
No, we don't know what ZymoGenetics sales are other than what we read in a press release from analysts or from their own public statement, so all I can say is that we definitely are way ahead of ZymoGenetics in terms of sales.
Erik Schneider – UBS
Okay. And what we've heard from them is that they're having trouble selling the product and in fact they're seeing pricing pressure in that market, particularly, with hospitals focused on saving money where they can. Have you seen anything like that with either Evithrom or that could be affecting Evicel going forward?
Robert Taub
No, I think that I mentioned in my script that there is a fierce price competition in the thrombin area, and I think ZymoGenetics itself is triggering that. So yes, there's tremendous competition in pricing currently ongoing, but we haven't seen anything in Evicel or in the (inaudible) area. So I don't think it's an overall statement here that has to be made about the Zymo stats in the United States, but rather a very specific thrombin related situation with Kings, ZymoGenetics, Ethicon and Omrix.
Source - seekingalpha

Omrix Ethicon - We're number 2 in Thrombin

During Omrix Q2 discussion was made on Evicel, Quixil, Evithrom, the Fibrin pad and a mystery bonus product that was just icing on the earnings cake. Revenue was up 72% year over year, led by Johnson & Johnson's Ethicon's 155% jump in sales of Omrix's biosurgical products. Most of that likely came from improved sales of Evicel -- its fibrin sealant used to stop surgical bleeding. The product was approved for use in all surgeries earlier. CEO Taub stated the obvious for the thrombin market "I'll rank the three competitors, King one, Ethicon/Omrix two and ZymoGenetics three."
On Ethicon intiatives with Evicel:
“a focus on burns and orthopedics and plastic surgery”
“an updated evicel website”

On Quixil:
“growing nicely” in Europe especially in Orthopedics.

On Evithrom:
continued “moderate growth” approx. 40% of purchasers were first time buyers.

On Fibrin Pad trials in Israel and USA:
ongoing but on target
anticipating approval first half 2010

On major costs:
Plasma costs expected to rise

On the “mystery” $ 1.9 million contributing by-product of Omrix plasma preparation:
It is an imuno-therapy product not a biosurgical
A 3 year contract is in place to continue selling these previously discarded by-products
The product is used on humans
Contractually unable to release name or country of partner

Consultancy hired by Omrix to Assess Fibrin Patch

Omrix, as you know are conducting a trial for a fibrin pad, which at a selling point of $500 will enter the market 2008 with US unit sales of 20,853 capturing 20% of the market share (according to the 2005 un-updated report at Omrix website, link below). This is expected to grow to a peak of 70% of the market by 2013.
While EMS and military use is apparently not the main focus for sales, it appears the US market is the main target further aimed at "less price sensitive" surgeons.
I am sure Ethicon must be preparing for a mighty unveiling and market entry, still one wonders whats going on with this talk of J&J woundcare sale? For Ethicon the Fibrin pad is probably a good strategy for moving some of that human sourced Evithrom (another Omrix thrombin product). As the recently funded $100 million for Zymogenetics with their recombinant product recothrom hits the stage.
Patch revenues are estimated to total over half a billion dollars within 10 years of launch. Further figures mentioned estimate the European market at 50% of the US and the ROW at 45% of the US market. Similar growth is anticipated in Europe and ROW as Stateside.
The full Pdf is available at the Omrix site or HERE is a link.

Johnson & Johnson is considering selling its wound-care business

Johnson & Johnson is considering selling its wound-care business to a private equity group, One Equity Partners. I don't think Johnson & Johnson's investors should really care one way or another; the unit's $270 million in sales last year made up less than 1% of Johnson & Johnson's revenue. But investors in picking Omrix Biopharmaceuticals should pay very close attention to the deal.
Johnson & Johnson's wound-management division markets all of Omrix's biosurgical products, and the two are also working together to develop a fibrin patch that combines a physical barrier with a biologically active component to stop bleeding.
The health-care conglomerate has until Aug. 22 to decide whether it will accept the offer for an undisclosed amount of money. (You can get away with these types of vague press releases when you're as large as Johnson & Johnson.)
Unsurprisingly, there's not quite enough information in the press releases and 10-Ks to know exactly what will happen, but let's check out the possibilities:

• Johnson & Johnson retains the right to sell Omrix's products, even though it's selling off its wound management business. That doesn't sound like the best option for Omrix, since having the sales reps hocking related wares likely helps move Omrix's own products.
• The partnership transfers to the new owners unchanged. This would be a big unknown for Omrix; One Equity could provide additional support for Omrix's products, but the backing of Johnson & Johnson sure sounds a lot better.
• A change in ownership allows Omrix to break out of the partnership. This could be an advantage to Omrix, if it can get a better deal from another company that sells wound management products, like Kinetic Concepts or Covidien.

Johnson & Johnson hasn't been doing terribly well against ZymoGenetics and King Pharmaceuticals in the battle of the thrombins since Omrix's version came on the market last year. But it has been doing a good job pushing Omrix's Evicel -- its fibrin sealant used to stop surgical bleeding. If J&J does decide to bid Omrix adieu, it'll likely do so with mixed feelings.

Source: Motley Fool

Plasma Derived Products:Pathogen Safety of EVITHROM™

Here is a link through to a presentation by Bernard Horowitz, Ph.D. discussing the safety of (Omrix manufactured) J&J's Evithrom, you have to register first.

Omrix do concede that "Our products are derived from human plasma, and are therefore subject to the risk of biological contamination inherent in plasma-derived products. This risk could adversely affect our ability to obtain raw materials and market our products. " In THIS document

Info from Omrix Biopharmaceuticals tells us Bernard Horowitz, Ph.D. has served as a member of our Board since February 2006. Since January 2000, he has been a principal of Horowitz Consultants, LLC, a company providing assistance in strategic planning, process development, viral safety, clinical trial design and new product regulatory compliance. From 1995 to 1999, Dr. Horowitz served as chief scientific officer, executive vice president and director of V.I. Technologies, Inc., now Panacos Pharmaceuticals, Inc., a now publicly held company he helped found as a spin-out from the New York Blood Center. Dr. Horowitz has served as a scientific consultant to the National Institutes of Health, the Food and Drug Administration, the National Hemophilia Foundation, the International Association of Biological Standardization, and the World Health Organization. Dr. Horowitz is a co-inventor of over 25 issued U.S. patents. Dr. Horowitz received his B.S. in biology from the University of Chicago and his Ph.D. in biochemistry from Cornell University Medical College. He is a director of Protein Therapeutics, Inc.

Recothrom, Evithrom, Thrombin JMI

Anyone interested in Thrombin, Zymogenetics, King and J&J should follow this blog by Joe Tartakoff.
During last week's ZymoGenetics conference call, Ed Tenthoff of Piper Jaffray asked ZymoGenetics CEO Bruce Carter if he was noticing any moves by Johnson & Johnson.
Here's the exchange:
Tenthoff: Can you just update us on where pricing is for RECOTHROM and how some of the competitors have responded, and there's, you know, we've noticed very little in terms of noise from Evithrom ...
Carter: With the bovine thrombin, we are seeing a limited discounting... And like your search for J & J (Johnson & Johnson), I guess it's fair to say they are out there, but perhaps not as much as one might have expected from the name Johnson & Johnson. In fact, I could go stronger, surprisingly little considering it's Johnson & Johnson.
Omrix Biopharmaceuticals, which sells Evithrom along with Johnson & Johnson, begs to disagree.
During Omrix's conference call to report its results, CEO Robert Taub was asked how he would characterize "your market share for thrombin versus competitors, including both King and ZymoGenetics."
His response:
"I think we -- well we'll put it this way. Obviously our market share of thrombin is lower than King and it is higher than ZymoGenetics."
Then, another analyst pressed him on why that was the case, considering that the conceptual risks associated with cow-derived thrombin (that patients would develop antibodies against the product) would probably be the same with a human-derived one.
Taub's response:
Bovine thrombin has been around for so many years, and the arguments about antibody formation, it's not very convincing and you have to be very careful. I heard that the FDA gave a warning just two or three days ago to some very aggressive promotional literature by ZymoGenetics on that. So the need, if you want, to change is not very high. So I think what's really driving it is contracts, introduction in the hospitals, bundling, and sales mention and service at this stage.
Still, Taub conceded that the thrombin market was a difficult one to break.
In a release last week announcing its first-quarter results, the company said Evithrom sales "continue moderate growth." Read the release here.
And during the call, Taub used the word "slow" twice to refer to the market for thrombin:
... As we have expected the stand-alone thrombin market is and will change slowly. It's a slow process. While stand-alone thrombin will continue to to be an important product, we also continue to believe that long-term thrombin growth will ultimately be driven by thrombin-based enhanced hemostats, where thrombin is combined with other agents such as various forms of gelatin and which will be easier to use.
Overall, it seems that Evithrom is running into many of the same hurdles as ZymoGenetics, which is having to wait for hospitals that have used the King product for years to vote to allow the use of Recothrom.
Taub:
... There seem to be very low awareness of any risks related to bovine thrombin. And the manufacture of bovine thrombin has been sitting on their market position for a long time and the ramp up is slow, because of the P&T (hospital) committees, and these contracts that have to be done... There is also less way to innovate unless you develop, which we are planning and doing with J & J.
Source: SeattlePI

Recothrom's April sales

Kevin DeGeeter, an analyst at Oppenheimer & Co., put out a report today saying that Recothrom, ZymoGenetics' treatment to stop bleeding during surgery, had $92,589 in April sales, substantially below his estimate of $750,000 for the month. He cited IMS, the market research firm.
By contrast, April sales of King Pharmaceuticals' Thrombin-JMI, which directly competes with Recothrom, jumped 11.5 percent to $23 million, according to IMS.
King has dominated the market for more than a decade and is now facing competition from both Recothrom (which was approved by the FDA in January) and Johnson & Johnson's Evithrom (which went on the market last year).
DeGeeter -- who has been bearish on Recothrom's prospects since its launch -- says:
"While we acknowledge the limitations of monthly sales data, the IMS numbers are not consistent with the upbeat comments from ZGEN management on the pace of product adoption.
ZymoGenetics has said that most of Recothrom's sales will take place during the second half of the year. Because Recothrom is bought by hospitals, committees at those institutions have to meet in order to decide whether to add the treatment to the selection of products that doctors can choose from to use. The process can take six months or more."
I e-mailed ZymoGenetics spokeswoman Susan Specht and asked whether the April sales numbers were in line with the company's expectations.
She said:
"The selling process is a long one and could take six months or more to work through with each hospital. We're making progress and expect that work to pay off in the second half of the year."
Source: The Life Sciences Blog