Status: approved and marketed

Organizations involved:

Fidia Farmaceutici S.p.A. – Manuf.; R&D; Tech.;

Sanofi SA – World mark.

OrthoLogic Corp. – Former

Description: Hyalgan is a viscous solution consisting of a high molecular weight (500—730 kDa) fraction of purified sodium hyaluronate derived from male chicken (rooster) combs in buffered physiological sodium chloride sollution having a pH of 6.8—7.5. Hyalgan is packaged in 2 mL vials or 2 mL pre-filled syringes. Each vial or syringe contains: sodium hyaluronate, 20.0 mg (10.0 mg/1.0 mL); sodium chloride, 17.0 mg; monobasic sodium phosphate.2H2O, 0.1 mg; dibasic sodium phosphate. 12H2O, 1.2 mg; and Water for injection (fill up to 2.0 mL).

Nomenclature: Hyaluronic acid/Sanofi [BIO]; Hyalgan [TR]; Hyaluronan injection [FDA]; sodium glucuronate-N-acetylglucosamine polymer [SY]; sodium hyaluronate [SY]

Companies.: Hyalgan was developed and is manufactured by Fidia Farmaceutici SpA.

U.S. marketing rights were originally held by OrthoLogic Corp. until assumed by Sanofi-Synthelabo Inc. in Oct. 1997, shortly after the product’s original U.S. approval and launch by OthoLogic. Hyalgan was then marketed in the U.S. by Sanofi Aventis Pharmaceuticals, Inc., a subsidiary of Sanofi Aventis S.A. (formed in early 2005 from the merger of Aventis S.A. and Sanofi-Synthelabo S.A.), with Fidia handling interational marketing. In Sept. 2011, Fidia assumed U.S. marketing from Sanofi, effectively assuming worldwide marketing.

FDA class: Medical Device PMA

Approvals: Date = 19970528; PMA (original medical device approval; P950027); Indication = for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy, and to simple analgesics, e.g., acetaminophen

Date = 19991218; PMA supplement; Indication = approval for labeling to be modified and to add information about the current clinical experience

Date = 20000830; PMA supplement; Indication = approval for labeling to be modified and to add information about the current clinical experience

Indications: [full text of the "Indications” section of product insert/labeling]:

Hyalgan is indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy, and to simple analgesics, e.g., acetaminophen.

Status: Fidia filed the PMA (medical device application) for Hyalgan for osteoarthritis of the knee on July 28, 1995, and FDA granted original approval on May 28, 1997. Hyalgan was the first FDA-approved hyaluronan therapy to treat osteoarthritis knee pain.

On Sept. 20, 2005, FDA accepted a PMA supplement to expand the indication of Hyalgan to include treatment of shoulder pain due to osteoarthritis or osteoarthritis in association with rotator cuff tears and/or adhesive capsulitis in patients who have failed to respond adequately to conservative nonpharmacologic therapy, and to simple analgesics, e.g., acetaminophen. Hyalgan had previously been approved for the treatment of pain in osteoarthritis of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy, and to simple analgesics, e.g., acetaminophen.

Hyalgan is marketed in various European and other countries. It has not received centralized European Union approval.

Medical: Hyalgan, like other hyaluronic acid knee viscosuppplementation products, is administered by intra-articular injection. A treatment cycle consists of five injections given at weekly intervals. Some patients may experience benefit with three injections given at weekly intervals. This has been noted in studies reported in the literature in which patients treated with three injections were followed for 60 days. Most people get months of pain relief from one course (3-5 weekly injections). The length of pain relief may vary based on your individual response. If pain returns, another course of treatment may be appropriate.

Marketing: The 2007 Average Wholesale Price (AWP) is $146.01 for either 2 mL prefilled syringes or vials.

Like similar hyaluronic acid products used for knee viscosupplementation, Hyalgan is reimbursable under Medicare., and is also reimbursed by a majority of private insurers and health plans.

In Sept. 2011, Fidia reported "More than 38 million doses of HYALGAN have been administered worldwide since its introduction."

In Dec. 2012, Sanofi agreed to pay $109 million to resolve kickback charges that free units of Hyalgan were used to induce physicians to purchase and prescribe the treatment. Sanofi was also accused of submitting false average sales price reports that failed to account for the free units, which caused federal healthcare programs to overpay for the product.