Cancer Vaccine THERATOPE® — Biomira

Abstract

Biomira is developing a therapeutic cancer vaccine [THERATOPE®] for treatment of breast and other cancers.¹ THERATOPE® consists of the mucin antigen, sialyl-Tn (STn), a carbohydrate located on the surface of breast, colorectal and ovarian cancer cells, conjugated to keyhole limpet haemocyanin (KLH).

Merck KGaA has acquired a worldwide licence to THERATOPE® for treatment of breast cancer. Under the terms of the licence, Biomira and Merck KGaA, via its US affiliate, EMD Pharmaceuticals, will jointly market the vaccine in the US. Merck KGaA holds exclusive marketing rights for the rest of the world, except in Canada (where Biomira retains rights), Israel and the Palestine Autonomy Area. Merck KGaA is now collaborating on phase III development for breast cancer. Biomira stands to receive $US150 million in licence, milestone payments and equity investments. The development costs will be shared between the two companies in North America but Merck KGaA will be solely responsible for these costs in countries outside the US.

Previously, Chiron Corporation had purchased a licence to THERATOPE® in 1997; however, Chiron terminated this agreement in June 2000. Under the terms of the termination, Biomira paid Chiron $US2.25 million to compensate the company for its investment in the development of THERATOPE®. In addition, Biomira will make another payment of $US3.25 million to Chiron upon FDA approval of the vaccine. No further payments or royalties will be made.

In the third quarter of 2002, an independent review of interim data from the trial was conducted. This was the fifth scheduled review of the data by the Independent Data Safety Monitoring Board (DSMB), all of which produced a positive response. Following the completion of the review, the DSMB stated that the trial should continue and that it had no safety concerns regarding this trial. Although the data, to which Biomira and Merck KgaA are blinded, did not meet the predetermined statistical significance for either endpoint at the time of the review, both companies have chosen to continue with the trial. Biomira has since announced that the p-value for the interim survival analysis was set at 0.01, while it is set at 0.03 for final survival analysis. The tighter criteria was set for the interim analysis to potentially give the companies the opportunity of applying for marketing approval earlier than expected. Final analysis of the trial will take place in mid-2003. If these analyses indicate therapeutic efficacy, Biomira will meet the FDA and Canadian regulatory officials to obtain marketing approval for the vaccine for breast cancer under the accelerated review guidelines. Assuming a best-case scenario, the vaccine could be filed for approval in 2004.

The phase III trial was initiated following positive preliminary results achieved in a bridging study in patients with metastatic breast cancer in the US and UK. Biomira announced final results of the bridging study in May 1999. The results confirmed that antibody titres against the STn antigen were significantly higher in patients treated with the improved formulation of THERATOPE®, compared with the corresponding titres of patients in the phase II trials of the old formulation of THERATOPE®.

In September 2002, the first patient was enrolled in a phase II THERATOPE® trial, which is enrolling patients with metastatic breast cancer who are taking either an aromatase inhibitor or fulvestrant. Approximately 95 patients will be enrolled in the trial at up to 12 US sites. The study is primarily designed to evaluate THERATOPE®’s ability to induce an immune response in these patients. However, the safety and tolerability of the aromatase inhibitor plus THERATOPE®, and the fulvestrant plus THERATOPE® combinations will also be evaluated. The trial has not been designed to evaluate the efficacy of the two combinations.

The US FDA has granted fast-track status to THERATOPE® for development as an adjunct to first-line combination chemotherapy in responding patients with metastatic breast cancer.[1]

A phase II trial in patients with metastatic colorectal cancer has been completed in the US; positive preliminary results from this trial were released in May 2001.[2]

On 24 November 1999, Biomira announced that it had licensed two patents covering methods of preventing growth of cancer cells expressing a mucin-type glycoprotein. The patents have been issued in the US and are pending in Japan and Canada. When issued in Japan, the patents will provide additional protection for THERATOPE® in that country. The patents were licensed from Dr Sen-itiroh Hakomori of the Biomembrane Institute in Seattle, with whom Biomira has also entered into a research collaboration.

Biomira announced in April 2003 that following examination of its re-issue application by the US Patent and Trademark Office, its patent 5 798 090 was reissued (RE 38 046) with additional claims. These additional claims represent broader patent coverage. The additional coverage will last until 2015.

Earlier, in February 2000, Biomira announced an expansion of equity line for up to $US100 million; a 3-fold rise that was done without any additional shares of Biomira stock being issued.

In June 2002, Biomira stated that it believes the market size for THERATOPE® in the US, Europe and Japan to be approximately 184 000 patients for the indication of metastatic breast cancer, of which the US would be 100 000, Europe 75 000 and Japan 9000. For the indication of colorectal cancer, the total market population for THERATOPE® is expected to be 183 000 patients, of which the US has been estimated at 100 000, Europe 75 000 and Japan 9000.