Neocartilage Clinical Trial

[knee deep in Goo]

Zimmer Holdings and ISTO Technologies Announce Start of Neocartilage Clinical Trial

(WARSAW, IN and ST. LOUIS, MO) February 15, 2007—Zimmer Holdings, Inc. (NYSE and SWX: ZMH), a leader in the orthopaedics industry, and ISTO Technologies, Inc., an innovative orthobiologic company, today announced that the clinical trial is now underway for Neocartilage, a living tissue-engineered graft under investigation for the restoration of cartilage defects, reestablishment of joint function and relief of pain in the knee. Zimmer plans to market the product as DeNovo® ET Engineered Tissue Graft.

In June 2006, the U.S. Food and Drug Administration (FDA) approved ISTO’s Investigational New Drug (IND) application, allowing the companies to move forward with human clinical trials of the novel cartilage regeneration treatment.

Jack Farr II, M.D., an orthopaedic surgeon with OrthoIndy, Indianapolis, performed the surgery on the first patient in November 2006.  “I have participated in a variety of projects involving cartilage repair and regeneration, and I find the science behind DeNovo ET very compelling,” said Dr. Farr.  “The initial surgery went as we had hoped, and we look forward to enrolling more patients into the study and serially assessing their progress with the implant.”

Kevin F. Bonner, M.D., an orthopaedic surgeon with Jordan-Young Institute in Virginia Beach, Virginia, has also enrolled patients into the study.  “In pre-clinical studies, DeNovo ET has demonstrated the ability to resurface cartilage defects,” said Dr. Bonner.  “The procedure is straightforward and builds on earlier cartilage repair techniques.”

Additional study sites for the clinical trial are being added.  Recently, Rush University Medical Center in Chicago was added; Dr. Brian Cole, the head of Rush’s Cartilage Restoration Center, will serve as the principal investigator for the Rush location.

Zimmer and ISTO entered into a co-development agreement in 2002 granting Zimmer exclusive worldwide commercial distribution rights to the Neocartilage technology.  The two companies have since collaborated on further development and pre-clinical testing. The potential market for DeNovo ET is large, as each year in the United States alone approximately 500,000 cartilage lesions are treated in knee joints.

“We are delighted both to advance the Neocartilage technology into human clinical trials, and to be collaborating with the world’s leading orthopaedic company to achieve this significant milestone,” said Mitchell Seyedin Ph.D., President and Chief Executive Officer of ISTO.

“Zimmer has made biologics the centerpiece of our innovative investment strategy and we are pleased to have reached this very concrete milestone in the development of our plans,” said Ray Elliott, Chairman, President and Chief Executive Officer of Zimmer Holdings.  “With our investments in other biologic repair and regeneration technologies, we intend to play a leadership role in the next generation of treatments to address the needs of patients with arthritis and other orthopaedic issues.”

DeNovo ET is a living tissue graft grown from juvenile chondrocytes (cartilage cells) using ISTO’s proprietary cell-based platform technology.  Studies have demonstrated that juvenile chondrocytes produce cartilage significantly better than their adult counterparts.  Cartilage works as a low friction articulating surface to protect joints from wear and tear experienced during motion.  Articular cartilage can be damaged as a result of injury, or can simply deteriorate over time leading to osteoarthritis.  Cartilage is known to have limited capacity to heal on its own.  Most joint replacements are performed as a result of the effects of osteoarthritis.

Zimmer is also developing another cartilage repair product in conjunction with ISTO.  The DeNovo NT Natural Tissue Graft also consists of juvenile chondrocytes in the form of minced cartilage tissue.  This living tissue graft is also intended to support the surgical repair of damaged articular cartilage.

. http://www.zimmer.com/z/ctl/op/global/action/1/id/9707/template/CP

[Jo-knee]

Wow, Can't wait to read more details of this.  Thanks Annie.

[oldfogy]

Hi ladies just to let you know i am apart of the program am having the surgery on June 6th with Dr Bonner.  Will keep you posted on all the stuff. There is alot involved  in the program. Nemerous MRIs and bloodwork. If you want any question asked just let me know.

[oldfogy]

hi guys

Just to let you know have done all the required stuff. First was the MRI not to bad. Then to the Red Cross to get a pint of blood drawn,they need that to make the fibrin glue. Then more bloodwork today for the rest of the stuff. They had to send some off to other labs.   Did find out 6 week NWB then 6 more weeks PWB. Thats a long time will be on here alot.  Mary

[skb]

hi guys

Just to let you know have done all the required stuff. First was the MRI not to bad. Then to the Red Cross to get a pint of blood drawn,they need that to make the fibrin glue. Then more bloodwork today for the rest of the stuff. They had to send some off to other labs.   Did find out 6 week NWB then 6 more weeks PWB. Thats a long time will be on here alot.  Mary

I posted this elsewhere, but again, good luck and keep us posted!

[pfokus]

Hi Mary,

How did everything turn out for you?  I hope it went well.  I have the option of getting the DeNovo ET procedure and interested in learning about any successes and failures.

Thanks,

Paul

[oldfogy]

 :'(Not well pfokus, did not work for me. I believe i was the only one that it did not work on. Have since had a tranplantation from a donar.  Still not sure how that is working. My patella is not very stable and does not hold in the groove well. Havew been in a unloader brace and patella brace. Wish they made one for both

[lizlove2110]

How long ago did you have the procedure?  Did you elect DeNovo NT or ET?

I'm planning on having the DeNovo NT procedure in April 2010.  Any advice?
Thanks.

[oldfogy]

The best advice I can give you is to do exactly as they tell you with the nwb and pwb. Be prepared to not do a whole lot. Therphy is a must and they must know what they are doing or  it will mess the whole thing up. Mine was the only one that was not sucessful. I am now waiting on a date and time for a total knee replacement.  It has been almost three years now. I   did not elect  to have they decided since it was a trial.

[skierboy]

Oldfogy--

Did the doctor(s) give you any explanation or indications as to why your participation in the clinical trial was not successful?  Given your "handle", are you over 50 or under 50 years of age?  I have heard that any clinical trials like this are done with people no older than 50.  But in this case, given the juvenile age of the materials being inserted, I would think (and certainly hope) that the DeNovo materials would be usable by patients of almost any age--assuming they can handle and do follow the rigorous post-op requirements of NWB and PWB for several months.