GAITHERSBURG, Md. _ An FDA advisory panel recommendedWednesday that Biomatrix Inc.'s treatment for osteoarthritis of theknee, be approved under the condition that post-marketing studies arecarried out to establish long-term safety and effectiveness.
In a 7-2 vote the Orthopedic and Rehabilitation Devices Panel of theMedical Devices Advisory Committee recommended that the FDAapprove the Ridgefield, NJ company's viscoelastic support product,Synvisc.
Biomatrix CEO Endre Balazs told BioWorld Today, "This is a newmedical paradigm: using viscoelastic supplementation in humans."
Synvisc is a highly viscous material made from hyaluron _ a naturallubricant, shock absorber and tissue stabilizer that the companypurifies from rooster combs. Synvisc is comprised of two differenttypes of hyaluron: a fluid type called hyaluron A and a very viscouscrosslinked type called hyaluron B.
Because osteoarthritis significantly decreases the amount of hyaluronin the synovial fluid of the knee, the disease decreases the joint'sability to absorb the impact of daily activities such as walking.Synvisc is designed to be injected once a week for three weeks intodiseased knees and serve as a fluid prosthesis for the synovial fluid.The viscosity provides protection for the joint.
Biomatrix presented animal data and data from five clinical studiesfrom Germany, Canada and the U.S. that showed that the product hadno significant long term adverse effects and that the only initial sideeffects were redness and swelling at the injection site. The companyalso showed that of patients who underwent the Synvisc injections 56percent were pain free at the end of 12 weeks whereas only 12percent of those who received saline injections had no pain. TheSynvisc patients did at least as well as patients who were onnonsteroidal anti-inflammatory drugs (NSAID) _ typically thesecond line of treatment for osteoarthritis.
Statistical Analysis Questioned
And, the effect remained out to 26 weeks even though the productwas shown to be very short lived in the joint: 39 percent of thetreated patients had no pain and only 13 percent of the controlpatients had such relief.
While the FDA agreed that the product was safe, in its presentationFDA reviewers questioned Biomatrix's statistics showing thatSynvisc benefited patients above the placebo effect. Panel memberM.Clinton Miller III, professor emeritus of biometry andepidemiology at the Medical University of South Carolina, told thecompany that he "had a lot of problems with the statistical analysis.You have demonstrated safety without question; efficacy is not nearlyas clear."
However, later in the discussion the question of long term safetycame to the forefront. Because the treatment effect inexplicablylasted for 26 weeks, some panel members brought up the possibilityof a delayed hypersensitivity to the treatment. Biomatrix counteredthat animal studies of Synvisc showed no hypersensitivity or jointdamage in monkeys that had received the equivalent of 8 cycles ofSynvisc treatment.
At the end of the discussion, panel member Harvinder Luthra, chairof the department of rheumatology at the Mayo Clinic, in Rochester,Minn., proposed that the panel recommend approval to the FDA withthe conditions that the company carry out postmarket studies todetermine long term effects, an assessment of quality of life benefitsof the treatment, to determine the effect of multiple courses oftreatment and that the labeling be limited to one course of therapy.The motion passed 7-2.
Lee Simon, a rheumatologist at Harvard Medical School, votedagainst the measure on the grounds that such studies represented thetype of data that should be prepared for approval in the first place.
Barbara Boyan, professor of orthopedic research at the University ofTexas Health Sciences Center, in San Antonio, on the other hand,voted against the measure because, she said, "the conditions are tooharsh considering the fact that the company has proven the product tobe safe and at least as effective as NSAIDs."
On Thursday, the committee also unanimously recommended a lessviscous hyaluron product produced by Fidia Pharmaceuticals, Inc., inWashington, for approval. Like Biomatrix, the recommendation camewith conditions for postmarket studies that included determining thenumber of injections necessary to have an effect. Company presidentRoberto Fiorentini noted that Hyalgan "will be our first U.S. productand should help us overcome some of the financial difficulties wehave experienced."
Synvisc has approval in several European countries and carries 50percent of the market for this type of treatment according to Balazs.
Biomatrix (NASDAQ:BIOX) closed at $15.25 down $0.25 onThursday. Fidia is privately held. n
-- Lisa Seachrist Washington Editor
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