CHIRON VISION FILES U.S. FDA APPLICATION TO MARKET DRUG DELIVERY IMPLANT FOR TREATMENT OF CMV RETINITIS; Signs Supply and Co-promotion Collaboration with Roche.

EMERYVILLE, Calif. and NUTLEY, N.J.--(BUSINESS WIRE)-- July 5, 1995--Chiron Corporation (NASDAQ:CHIR) and Hoffmann-La Roche announced today that Chiron's ophthalmic business, Chiron Vision, has filed a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) to market Vitrasert(TM), its intraocular implant which delivers ganciclovir directly to the eye for treatment of cytomegalovirus (CMV) retinitis. CMV retinitis is the most common opportunistic infection and leading cause of blindness in people with AIDS. Currently, physicians can treat the disease with I.V. ganciclovir, foscarnet or oral ganciclovir.

The NDA filing is based on results of two independent Phase 3 clinical trials conducted by Chiron Vision and The National Eye Institute (NEI). The studies demonstrated that the Vitrasert ganciclovir implant offers a clinical improvement versus intravenous ganciclovir in further delaying progression of CMV retinitis in the treated eye.

Also today, Chiron Vision and Hoffmann-La Roche Inc., a member of the Roche Group, announced a collaboration to market and co-promote Vitrasert. Chiron Vision developed the Vitrasert implant technology and Hoffmann-La Roche currently markets Cytovene(R) (ganciclovir), the drug used in the implant. Roche will provide ganciclovir, which was discovered and developed by Roche Bioscience (formerly Syntex), another member of the Roche Group, on an exclusive, worldwide basis for use in the eye implant. Roche Bioscience also brings its substantial patent portfolio, regulatory position and technical expertise with ganciclovir to the collaboration with Chiron Vision.

In the collaboration, Chiron Vision will develop, manufacture and sell the Vitrasert for CMV retinitis. The two companies will co-promote the Vitrasert, with Chiron Vision focusing on the ophthalmic surgeon and Hoffmann-La Roche focusing on the primary care and infectious disease physicians.

"We believe that the Vitrasert implant represents a major step forward in the treatment of a tragic condition that robs many people with AIDS of vision," said William J. Link, Ph.D., Chiron Vision chairman and chief executive officer. "This filing culminates a model three-year collaboration between the NEI, community based groups representing HIV-infected people, and Chiron Vision. On behalf of all these collaborators, I want to thank the clinical investigators and study subjects whose participation and dedication made this achievement possible."

"Our agreement with the Roche Group enables us to accelerate the introduction and widespread availability of this important product," Link continued. "With the inclusion of ganciclovir NDA reference rights from Roche Bioscience, our filing contains all the information necessary for a rapid FDA review. Once Vitrasert has received market approval, Hoffmann-La Roche, in Nutley, will co-promote the product through its U.S. sales force that has supported the adoption of ganciclovir as the current standard of care for CMV retinitis; F. Hoffmann-La Roche Ltd., Basel, will market the product through its international distribution network. Physicians caring for HIV-infected patients will be essential in providing information about the benefits of this new therapy to as many potential CMV retinitis patients as possible. Chiron Vision has developed a network of ophthalmic surgeons who are experienced with the Vitrasert, and has a leading worldwide ophthalmic surgical business through which the Vitrasert will be sold."

"Clinical studies have repeatedly shown the benefit of the intravenous and oral form of Cytovene (ganciclovir) in the treatment of CMV retinitis. Our collaboration with Chiron Vision ensures that people with AIDS have an additional option for using ganciclovir in the treatment of this disease," commented Dr. Franz B. Humer, Head of the Pharma Division of the Roche Group. "Roche Bioscience is presently conducting a study to determine the importance of providing systemic coverage (oral ganciclovir) in addition to the Vitrasert to reduce the risk of development of extraocular CMV disease or CMV retinitis in the contralateral eye."

Data from a planned interim analysis of the multi-center, controlled, randomized Chiron Vision study, testing the implant in 188 AIDS patients with newly diagnosed CMV retinitis, was reported January 31 at the National Conference on Human Retroviruses and Related Infections in Washington D.C. The study demonstrated that the median time to progression of CMV retinitis was 186 days for eyes receiving Chiron Vision ganciclovir intraocular implants compared to 72 days for eyes receiving intravenous ganciclovir therapy (p less than 0.0001). The incidence of extraocular CMV disease was 12 percent in the implant arms versus 0 percent for I.V. ganciclovir. There were few serious surgical complications. The complete analysis of the data, upon which Chiron Vision's FDA submission is based, confirmed these results.

Study participants were assigned randomly to an IV ganciclovir group or one of two implant group (1 microgram/hour or 2 micrograms/hour) and were followed for eight months or until progression of retinitis or death. Progression of retinitis was determined by a central masked Fundus Photograph Reading Center at the University of Wisconsin.

Results of the NEI study, published in the December 14, 1994, issue of the Archives of Ophthalmology, showed that AIDS patients had no progression of newly diagnosed, peripheral CMV retinitis for about eight months using the ganciclovir implant. Among those who received no immediate treatment, the eye infection worsened in about 15 days. The study evaluated 26 patients, of which 30 eyes were randomly assigned to either immediate treatment (patients received an implant within 48 hours of study enrollment) or deferred treatment (patients were evaluated until progression of CMV retinitis was noted).

The study found that in people who received immediate treatment (within 48 hours of enrollment) the ganciclovir implant eliminated all signs of active infection for a median of 226 days, or about eight months. Among study participants in the deferred treatment group, the median time to CMV retinitis progression was 15 days. During the study, most participants enjoyed good vision with the implant. By the final follow-up eye examination, 34 of the 39 eyes treated with the implant had nearly perfect vision (20/25 or better). However, nearly all affected eyes had blurred vision immediately after receiving the ganciclovir implant, and 18 percent of the eyes experienced retinal detachment, a common problem for people with AIDS with CMV retinitis.

CMV retinitis affects approximately 15 to 40 percent of people with AIDS. Current approved treatment with the antiviral drugs IV ganciclovir, oral ganciclovir or I.V. foscarnet delays progression of CMV retinitis for a median range of 50 to 75 days (Fundus photographs). Treatment with these systemic therapies requires twice-daily I.V. administration initially, followed by daily I.V. or oral administration.

Chiron Vision's intraocular implant, utilizing technology developed at the University of Kentucky and licensed from Control Delivery Systems, Inc., a company founded by the implant's inventors Paul Ashton, Ph.D., and Thomas Smith, M.D., contains ganciclovir embedded in a polymer-based system that slowly releases the drug into the eye for up to eight months. The implant is placed into the posterior segment of the eye through a 5 to 6 mm incision during a one-hour surgery performed under local anesthesia. The implant can be removed and replaced when depleted of drug.

Chiron Vision is preparing applications to market Vitrasert in additional countries. It plans to file such an application in the first of these countries, Canada, in July, followed by applications in several European countries this fall.

Currently, two additional clinical trials are underway to further evaluate the ganciclovir implant for CMV retinitis. Enrollment in these studies is limited to patients who meet certain eligibility criteria. For more information on these studies, contact the Professional Services Group at Chiron Corporation. The number is 1-800-C-H-I-R-O-N-8 (1-800/244-7668), select "2."

Hoffmann-La Roche Inc. of Nutley, N.J., and Roche Bioscience of Palo Alto, Calif., are both research-based health care companies that are members of the Roche Group with headquarters in Basel, Switzerland. Roche is a leading international health care company dedicated to the research, development and delivery of diagnostic tests, treatments and services for people with life-threatening diseases.

Chiron Corporation is a biotechnology company headquartered in Emeryville, California, near San Francisco. Chiron is building a healthcare business that addresses needs in several markets: diagnostics, including immunodiagnostics and bDNA probe assays; vaccines, emphasizing adult and pediatric infectious diseases; therapeutics, with an emphasis on oncology, endocrinology and serious infectious and other diseases requiring critical care; and ophthalmic products for the surgical correction of vision.

CONTACT: Chiron Corporation, Emeryville

Larry Kurtz, 510/601-2476

or

Hoffmann-La Roche Inc., Nutley

Gail Levinson, 201/562-2218