LONDON ¿ Xenova Group plc¿s treatment for genital herpes, TA-HSV, will be dropped after failing in a Phase II efficacy trial, and the development agreement with partner GlaxoSmithKline will be terminated in January.
CEO David Oxlade told BioWorld International he was disappointed. ¿But we have been signaling to the market for some time that the clinical challenge to [developing] a therapeutic product was acknowledged to be a very tough hurdle to overcome. Most analysts had a very modest amount in the share price for TA-HSV.¿
Despite its failure as an immunotherapeutic, Xenova will take TA-HSV forward as a vaccine.
The share price fell by almost 20 percent to end the week at 26.5 pence after the news was announced.
Xenova, based in Slough, UK, acquired TA-HSV when it purchased Cantab Pharmaceuticals plc earlier this year. It was the Phase II failure of a related product, TH-GW for the treatment of genital warts, being developed in partnership with then-SmithKline Beecham plc, which forced down Cantab¿s share price and made it an acquisition target.
The multicenter, placebo-controlled trial of TA-HSV involved 483 people infected with the herpes simplex virus and suffering from recurrent outbreaks. No significant difference was seen between the treatment arm and the control group in terms of time to first recurrence, the total number of recurrences or other clinical outcomes assessed during the course of the study.
¿Glaxo thought the preclinical and Phase I data gave very good grounds for taking the product into an extensive Phase II study. They were surprised and disappointed that it didn¿t show benefit,¿ Oxlade said.
The expectation was based on TA-HSV¿s ability to elicit an immune response. Although this failed to prevent outbreaks in people infected with herpes, Oxlade said the evidence is that it would prevent infection in people who are seronegative. ¿Hence, the vaccine program goes forward.¿
The Phase I trial of the vaccine, DISC-HSV, which reported in September 1999, showed a significant immune response in previously uninfected subjects. The magnitude of the response was similar to that seen in naturally infected subjects who are able to control their disease and therefore show no symptoms, and is believed to be appropriate for the prevention of both genital and oral herpes. Glaxo had rights to the vaccine but was forced by the U.S. Federal Trade Commission to return them as a condition of its merger with SmithKline Beecham.
Oxlade said the decision to carry DISC-HSV forward was supported by the failed Phase II TA-HSV trial, which ¿provided very valuable additional safety data in 480 more patients.¿ The only drug-related side effect was swelling at the site of the injection, in one subject. In addition, work carried out by Glaxo on manufacturing and scale-up will revert to Xenova.
Xenova will now do further work on the formulation and scaling up manufacturing before looking for a partner for DISC-PRO. Oxlade expects it to be ready for partnering in the next 18 months.
Despite the demise of TA-HSV and the previous failure of the genital warts treatment, which was based on the same construct, Oxlade said it should be possible to develop immunotherapeutics against viral diseases. ¿Although the field has not gone very well, things are often stated to be impossible until they are achieved. The data still gives reason to believe it will work. Otherwise [how do you explain] why some people are naturally immune?¿