International Adhesions Society





Adhesions: Business & Regulatory News


CoSeal® Surgical Sealant Shown to Inhibit Adhesions in Cardiac Procedures

PALO ALTO, CA -- September 20, 2001 -- Cohesion Technologies Inc., a leader in developing and commercializing BioSurgical products including surgical hemostats, sealants, adhesion prevention barriers and adhesives, today announced that CoSeal® surgical sealant was shown to significantly reduce the formation, tenacity and surface area of adhesions during cardiac surgery in preclinical models.
The results of this study were published in Heart Surgery Forum by lead author Marc Hendrikx, M.D., Ph.D., Department of Cardiothoracic and Vascular Surgery, Jesse Hospital, in Hasselt, Belgium, in an article entitled "Evaluation of a Novel Synthetic Sealant for Inhibition of Cardiac Adhesions and Clinical Experience in Cardiac Surgery Procedures."
In the study, CoSeal was compared with an approved fibrin glue and with a surgical control. Eighty-eight percent of CoSeal treated sites had no adhesions or had adhesions of low tenacity. In comparison, zero percent of the fibrin glue treated sites and 13 percent of surgical control sites had either no adhesions or adhesions of low tenacity. In addition, CoSeal significantly reduced the percentage of treatment area with adhesions as compared with the fibrin glue and the surgical control.

Commenting on the study, Dr. Hendrikx said, "We were amazed by the adhesion prevention properties exhibited by CoSeal in the study. The results were very impressive. In addition, we observed that CoSeal also sealed vascular grafts very effectively. Based on our work, CoSeal seems to have multiple important applications during cardiac surgery, addressing problems for which we currently have few therapeutic options."

Pericardial adhesions subject patients requiring re-operation to potential injuries to the heart, great vessels, and cardiac grafts during the re-sternotomy. These adhesions can severely complicate re-operations by making re-entry hazardous, impeding orientation and visibility, increasing the loss of blood, and prolonging the operating time.

"CoSeal has demonstrated significant potential in preclinical testing as an effective adhesion prevention barrier," stated Frank DeLustro, Ph.D., president and chief operating officer of Cohesion. "CoSeal's synthetic composition, quick and easy preparation and ability to adhere to tissue where it is applied and remain in place during the critical wound-healing period, could offer significant competitive advantages over the limited and cumbersome alternatives available today."

CoSeal is currently marketed as a surgical sealant in certain countries of Europe and in Australia. CoSeal is a completely synthetic, self-polymerizing liquid biomaterial that resorbs in less than 30 days. CoSeal, which can be prepared in less than two minutes, is easy to apply and adheres effectively to tissue to seal around synthetic surgical materials such as Dacron and PTFE. These product attributes are expected to provide significant competitive advantages in the crowded and hectic operating room setting.

SOURCE: Cohesion Technologies, Inc.


FDA wants new studies on surgical mesh implants

By Anna Yukhananov
WASHINGTON | Thu Jan 5, 2012 12:15pm EST
(Reuters) - U.S. health regulators ordered new safety studies for surgical mesh implants that are used to hold pelvic organs in place, citing a spike in the number of complications seen for female patients, including erosion and infection.
The Food and Drug Administration also said it may reclassify the devices in a higher-risk category that would require manufacturers, such as Boston Scientific and a unit of Johnson & Johnson, to conduct clinical trials in people before receiving approval for sale.
The companies could not be immediately reached for comment.
The devices, made of synthetic or biological material, are commonly implanted in women to repair weakened or damaged tissue and provide support in cases of pelvic organ prolapse (POP). They are also used to help those with a severe overactive bladder known as stress urinary incontinence.
The FDA said it received more than 1,500 reports of complications related to the repairs with mesh from 2008 to 2010, including cases in which the mesh eroded into the vagina or caused bleeding and infection. The rate of problems was five times the rate reported from 2005 to 2007.

The FDA sent letters this week to 35 manufacturers of transvaginal surgical mesh, requesting three-year studies of several hundred women each to study side effects, as well as the women's overall quality of life.
In July, the agency warned that complications with the mesh were "not rare" and that transvaginal organ repair using mesh may put patients at greater risk than other surgeries and treatments.
The FDA also said it was concerned about scientific studies that show a lack of clinical benefit from surgical mesh, compared to non-mesh repair.
About 75,000 women received mesh repairs for pelvic organ prolapse in 2010 and about 200,000 women received transvaginal repairs for stress urinary incontinence.
The agency is asking for more studies from companies that sell the mesh for POP surgery. In the case of mesh used to correct an overactive bladder, the FDA is seeking further study of use of a so-called "mini-sling," when strips of material are used around the bladder neck and the urethra.
During their lifetime, 30 percent to 50 percent of women may experience POP, with two percent developing symptoms. The condition happens when tissue that holds the pelvic organs in place becomes weak or stretched and bulges into the vagina.
Surgery to support prolapsing organs can be done through the abdomen or the vagina, either with stitches or also with surgical mesh for reinforcement.
Surgical mesh has been used since the 1950s to repair abdominal hernias, but doctors only started using the mesh for POP and stress urinary incontinence in the 1990s, a procedure that has grown in popularity.
Companies that wanted to make the mesh specifically for POP or urinary incontinence could submit their application under a 510(k) accelerated review application that did not require them to do clinical trials in people, as long as they could show their implants were similar to devices already on the market.
But during a panel meeting in September, outside advisers to the FDA recommended that the agency reclassify the devices for POP to require companies to submit additional studies. The FDA said it is considering their advice.
Jeffrey Grand, a lawyer at Bernstein Liebhard in New York, is representing women who are suing companies that make the transvaginal mesh, with a case going to trial later this year.
" These things were basically put on the market without any significant safety testing," Grand said. "I'm hoping that all of this brings about some regulatory changes."


Tyco International Signs Agreement to Acquire Confluent Surgical


PEMBROKE, Bermuda – July 18, 2006 – Tyco International Ltd. (NYSE: TYC, BSX: TYC) today announced that U.S. Surgical, a subsidiary of Tyco’s Healthcare segment, entered into a definitive agreement to acquire Confluent Surgical, Inc., a leading developer and supplier of polymer-based technology used in sprayable surgical sealants and anti-adhesion products. The transaction is priced at $245 million. The Boards of Tyco International and Confluent Surgical have approved the transaction, which is expected to close by the end of August. Tyco expects to incur a charge in its fiscal fourth quarter to write off in-process research and development.

Confluent Surgical, located in Waltham, Mass., markets a neurosurgical sealant that was the first product to receive Food & Drug Administration (FDA) approval for use in cranial dural repair. This sealant, along with several other products in the company’s pipeline, is intended to improve patient outcomes by reducing leaks or adhesions across various surgical specialties. Over the next six years, the biosurgery market—which is estimated at $900 million—is expected to double in size. This acquisition helps position Tyco Healthcare and U.S. Surgical to compete effectively in that growing market.


Angiotech Gets Positive Results in Study of Adhibit Spray Gel to Prevent Adhesions.

Wednesday September 28, 11:06 am ET
Angiotech Gets Positive Results in Study of Adhibit Spray Gel to Prevent Adhesions

NEW YORK (AP) -- Angiotech Pharmaceuticals Inc. said Wednesday it received positive results from a clinical study conducted to evaluate how safe and effective its Adhibit Adhesion Prevention Gel is in reducing scarring after uterine surgery.

Adhibit is a spray gel applied during surgery that binds directly to the tissue and creates a temporary barrier, preventing contact and adhesions from forming between tissue surfaces.

The company said the number of patients who suffered from adhesions in the control group was double that of the group receiving Adhibit -- 65 percent versus 33.3 percent. Safety data also indicated fewer adverse events occurring with the Adhibit group than the control group.

The study was conducted at six sites in Germany, Canada and Curacao. Patients who were scheduled to undergo myomectomy surgery were randomized to either receive Adhibit or be part of a control group. Patients then returned 8 to 10 weeks later for a second-look procedure and were evaluated for both extent and tenacity of adhesions.

Uterine fibroids are benign tumors of muscle and connective tissue that develop within, or are attached to, the uterus. Fibroids are the most common pelvic tumor and they may be present in as much as 70 percent of women, for which surgery is a common treatment.

"One of the major challenges to date has been to deliver an effective adhesion barrier through a laparoscope, a technique that requires only a very small scar as compared to the traditional and more disfiguring technique of open surgery," said Rui L. Avelar, senior vice president of medical affairs for Angiotech. "Adhibit is a sprayable and versatile adhesion barrier that can serve as a useful tool in women's health-care and gynecological surgery."

Adhesions occur when normally separate tissues scar together following surgery or tissue damage. Angiotech said the incidence of adhesions is remarkably high, particularly among patients with a history of multiple surgeries and women with previous gynecologic surgeries.

Adhesions can be life threatening and can make follow-up surgeries hazardous, and are also a leading cause of female infertility and bowel obstruction.

Currently approved in Europe to prevent or reduce post-surgical adhesions in pediatric patients undergoing cardiac surgery, Adhibit is a synthetic, self-polymerizing liquid hydrogel that is safely metabolized by the body in less than 30 days.

Adhibit is sold and marketed by Baxter Healthcare Corp., who also has an option to license Adhibit in the U.S., but it is currently not approved for sale in the United States.

Celebrex Prevents Adhesions After Surgery in Mice

Feb 4th 2005: The recent finding that Celebrex may help to reduce adhesions after surgery is a significant finding for several reasons. Although the study reported by Dr. Mark Puder and his colleagues at Children's Hospital in Boston was performed in mice there are several reasons for hope.

Principally, for the first time we have data that shows that an approved drug is active orally against adhesions. This provides important leads for future research. There is a long way to go before this drug should be used routinely in humans - there are a number of safety concerns not only related to surgery itself but also related to the ongoing controversy over the use of COX2 inhibitors, of which Celebrex is a type.

This landmark study was published in the online version of the
prestigious journal "Annals of Surgery" . Dr. David Wiseman, founder of the International Adhesions Society, had been invited along with two surgeons, to review the manuscript as part of the peer review process and was able to make some significant contributions regarding the presentation and analysis of the data obtained in the study. Somewhat unusually Dr. Wiseman was acknowledged in the paper, as "a reviewer."

"I sent the paper back about two or three times for revision because I wanted to make sure that there was nothing ambiguous about this landmark paper. I'm glad I was able to do my part to heighten the awareness about ARD and to offer hope to all of its victims."

Seprafilm® Efficacy Data Presented

Press Release Source: Genzyme Corporation

Seprafilm® Efficacy Data Presented at Surgical Meeting Shown to Reduce Incidences of Adhesive Small Bowel Obstruction Following Colorectal Surgery
Tuesday May 11, 10:34 am ET

CAMBRIDGE, Mass., May 11 /PRNewswire-FirstCall/ -- Genzyme Corporation (Nasdaq: GENZ - News) today announced clinical data were reported that show Seprafilm® Adhesion Barrier to be effective in reducing the incidence of adhesive small bowel obstruction following colorectal surgery. The data were presented at the annual meeting of the American Society of Colon and Rectal Surgeons in Dallas and come from a five-year study involving nearly 1,800 patients.

Seprafilm is a temporary, physical adhesion barrier for abdominal and pelvic adhesion prevention. Patients in this randomized, controlled, multi- center, international trial underwent one of several colorectal procedures, with the majority undergoing colon resection for inflammatory bowel disease. It is one of the largest clinical studies of its kind.

In the treatment group, Seprafilm was placed throughout the abdomen and pelvis with the intention to reduce the incidence of adhesive small bowel obstruction. The control group did not receive any anti-adhesion barrier. The incidence of bowel obstruction of any cause between the treatment and control groups did not differ. Such results were not unexpected because an obstruction can be caused by several factors, including bowel stenosis and strictures, anastomotic complications, and cancer -- conditions which would be unaffected by the placement of an adhesion barrier.

However, detailed analysis indicated that Seprafilm reduced the relative risk of a first adhesive small bowel obstruction by 47 percent (1.8% vs. 3.4%, treatment vs. control, respectively, p<0.05) in colorectal surgery patients where the outcome was verified by direct visualization. The study showed this led to fewer repeat operations for adhesive small bowel obstruction in the treatment group. There was no difference in the overall rate of adverse events between groups.

In earlier Seprafilm studies involving 342 patients, Seprafilm was proven to prevent adhesion formation following both abdominal and pelvic surgery. However, it was previously unknown if a reduction in adhesion formation would lead to a reduction in the occurrence of adhesive small bowel obstruction. These results suggest that Seprafilm successfully reduces the incidence of these events in patients undergoing colorectal surgery, leading to fewer repeat operations.

"These results are very encouraging and confirm that Seprafilm is safe to use for preventing adhesions in colorectal surgery patients," stated Lena Holmdahl, M.D., Ph.D., senior medical director, Genzyme Corporation. "We believe the data will demonstrate the link between adhesion reduction and clinical benefit that had been missing until now."

"These data confirm that prevention of adhesions with Seprafilm results in improved clinical outcomes, specifically a clinically significant reduction in the incidence of adhesive small bowel obstruction," said David E. Beck, M.D. of the Ochsner Clinic and a lead investigator in the trial. "We are encouraged by the results and are seeing increased use of Seprafilm in our institution as a result of our experience during this trial."

Questions regarding these data should be directed to Genzyme Medical Information at 1-800-745-4447.

About Seprafilm

Seprafilm Adhesion Barrier is indicated for the reduction of post-surgical adhesions in patients undergoing abdominal or pelvic laparotomy. Seprafilm currently is not labeled for use in preventing small bowel obstruction in colorectal surgeries.

Seprafilm is one of a series of hyaluronic acid-based products developed by Genzyme. The company's leadership in biomaterials is built on nearly two decades of pioneering work in the application of hyaluronic acid (HA) to medical and surgical uses. HA also is the basis of Synvisc® (hylan G-F 20) and the Hylaform® (hylan B gel) product lines. Genzyme is working to extend these products through significant development efforts and to explore areas where HA may have a medical advantage.

The most common adverse events in Seprafilm clinical trials, which were not different from untreated controls, include ileus, anastomotic leak, and abdominal abscess. Seprafilm should not be wrapped around an anastomosis, as such usage may result in increased anastomotic leak related events. Seprafilm has not been studied prospectively in pregnancies, in the presence of frank infections, or in malignancies.

About Genzyme Corporation

Genzyme Corporation is a global biotechnology company dedicated to making a major positive impact on the lives of people with serious diseases. The company's broad product portfolio is focused on rare genetic disorders, renal disease, osteoarthritis and immune-mediated diseases, and includes an industry-leading array of diagnostic products and services, and sophisticated biomaterials. Genzyme's commitment to innovation continues today with research into novel approaches to cancer, heart disease, and other areas of unmet medical need. More than 6,300 Genzyme employees in offices around the globe serve patients in over 80 countries.

This press release contains forward-looking statements, including the statements regarding the future prospects for Seprafilm and Genzyme's efforts to expand its portfolio of HA-based products to other applications through additional development work. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others, the uncertainties associated with conducting future clinical trials; the regulatory approval process for new products; competitive product development; the requirement for substantial funding to conduct additional research and development work relating to HA-based products; market acceptance of new products; the ability to obtain and maintain patent or other proprietary intellectual property protection and the actual impact of those patents and rights; and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation the information under the heading "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of the Genzyme Annual Report on Form 10-Q for the quarter ending March 31, 2004. Genzyme cautions investors not to place undue reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements.

Genzyme®, Seprafilm®, Hylaform® and Synvisc® are registered trademarks of Genzyme Corporation. All rights reserved.

Genzyme's press releases and other company information are available at and by calling Genzyme's investor information line at 1-800- 905-4369 within the United States or 1-703-797-1866 outside the United States.

Media Contact: Investor Contact:
Maria Foley Kristen Galfetti
(617) 768-6690 (617) 768-6563

Adhesions, Adhesions-Related Disorder or CAPPS – a way to think about the problem from the patient’s perspective.

Dallas TX. June 11 2010. The International Adhesions Society (IAS) is proud to post on its web site the results of groundbreaking and innovative research which will forever change the way the problem of adhesions is viewed.

The paper was published after Dr. Wiseman was invited to submit a manuscript for inclusion in a special volume of “Seminars in Reproductive Medicine” on the subject of adhesions. The paper is entitled: “Disorders of Adhesions or Adhesion-Related Disorder: Monolithic Entities or Part of Something Bigger—CAPPS? “ (click here for .pdf)

Since forming the International Adhesions Society (IAS) in 1996, it became increasingly obvious that the problems of patients suffering from adhesions were not just about adhesions. Accordingly, we were the first to coin the term “Adhesion Related Disorder” (ARD) to include the entire complex of pain, infertility, obstruction, nutrition, psychological and social issues that ARD sufferers and their families experience.

Based on formal patient surveys as well as thousands of emails and phone calls from patients, it became apparent to us that even the term ARD may be inadequate to address the problem. In reality, the ARD patient is part of a much larger group of patients who, in varying degrees, combinations and sequences experience a range of symptoms and conditions including endometriosis, interstitial cystitis (IC), irritable bowel syndrome (IBS), bowel obstruction and chronic abdominal and/or pelvic pain.

Although ‘‘adhesions’’ may start out as a single, stand-alone entity, an adhesions patient may develop a number of related conditions (ARD) which renders those patients practically indistinguishable from patients with multiple symptoms originating from other abdominal or pelvic conditions. (continued)

Click here for a pdf copy of the entire press release.

Click here for a .pdf copy of the CAPPS article

INTERGEL Withdrawn from Market by Company

GYNECARE Voluntarily Suspends Marketing and Sales of Anti-Adhesion Product Pending Evaluation of Postmarketing Events

Gynecare (division of Johnson & Johnson) have voluntarily withdrawn the anti-adhesion product - INTERGEL - from the market pending an investigation into the circumstances surrounding some adverse events including post-operative pain and inflammatory reaction. There were also two deaths where the product had been used after the accidental puncture of the bowel. The relationship between the product and these events is not certain, but the company are investigating it.


The IAS has been contacted by a number of patients who have asked us what to do if they believe they have had a reaction to Intergel. Gynecare (a division of Johnson & Johnson - the marketers of the product) have kindly provided us with the following announcement:

"If you have had Intergel used during a surgical procedure and have any questions about it or believe you have had a reaction to it, you may contact Gynecare directly by dialing 877-384-4266, option 1. This number will connect you with a Registered Nurse who is trained to respond to your call."

You may also contact your own doctor who will make a report to the company, since this information will be useful to them in determining the cause. (If you do contact the company, let your doctor know this so that s/he can inform the company). You can let us know too if you wish.

For more information you can read the following press releases (PDF), as well as a copy of the letter sent to doctors (PDF) and the FDA Safety Alert.

FzioMed's Oxiplex "Not Approvable" According to FDA Panel BY DAVID KRESSEL, JULY 16, 2008

On Tuesday, we attended the FDA's Orthopaedic & Rehabilitative Devices Panel, Oxiplex/SP was voted "Not Approvable" by a 5-2 vote, based largely on the sponsoring company's inability to definitively demonstrate product effectiveness. The two dissenters would have voted it "Approvable with Conditions".

Oxiplex is the lead product from FzioMed, a San Luis Obispo, CA-based biomaterials company. Oxiplex is used to prevent adhesions (peridural fibrosis), and is currently distributed by J&J and Medtronic outside of the US--it has been used in 100,000 surgeries to date. There is currently no FDA-approved product to treat spinal adhesions, though there are adhesion barriers that are approved for general surgery and ob-gyn indications. Oxiplex's indication would have been as a surgical adjuvant during posterior lumbar decompression surgery to improve patient outcomes by reducing post-operative pain. The pivotal study's primary efficacy endpoint was improvement in leg pain, as measured by the Lumbar Surgery Outcomes Questionnaire (LSOQ). Of note, the pilot study mentioned "reduction of adhesions" as the indication, but this was removed for the pivotal study.

FzioMed's presentation focused on a complicated "multivariate longitudinal” statistical analysis of the change in leg pain from baseline to six months by GEE (Generalized Estimating Equations)" which included ten covariates and five treatment-by-covariate two-way interactions. Their analysis showed that, in patients with more severe back pain before surgery, there was a statistically significant reduction in leg pain in the Oxiplex group.

The FDA's presentation focused on a series of simpler analyses, none of which demonstrated statistically significant reduction in pain scores. FDA's dataset was also different from FzioMed's because FDA included patients with results "out of window" for 6 month follow up (e.g. a patient who didn't visit their surgeon at 6 months after surgery, but 12 months after).

The panel sided with FDA and believed FzioMed's statistical method to be exploratory or post-hoc data mining. As one surgeon-panelist said, "I see complex data manipulation that I don't understand, and that worries me." Even the biostatisticians on the panel were skeptical of the validity of the analysis. The panel was able to unanimously concluded that Oxiplex:
-Was safe
-Addressed a significant clinical need
-Might be effective
-Did not prove effectiveness in its trial results

Disagreement surfaced over whether the product should be approved. Two panelists believed that the prospect of a potentially effective, positively harmless, product to treat an important problem with no other solution warranted approval.

Although many comments and questions from the panelists and FDA could have been judged as statistical nitpicking, the most interesting issue to arise was the fact that nobody, not even the company, had any clue as to how or why Oxiplex worked. FzioMed had a couple of unexplored hypotheses, but nothing else. Although concerning on its own, this also seriously undermined FzioMed's position regarding subgroup analysis, because if there is no understanding of the mechanism of action, there's no reason to trust post hoc analysis suggesting the product is more effective in a subgroup.

In the highly likely event FDA follows the panel's recommendation, it appears FzioMed will have to decide if it is interested in conducting a new clinical trial to prove efficacy in the subgroup of patients with worse baseline pain.




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