Staff Writer

Cancer vaccines are back in fashion, thanks to Dendreon Corp.'s recent Phase III success with Provenge (sipuleucel-T) in prostate cancer, and encouraging data presented this weekend at the American Society of Clinical Oncology's annual meeting sent shares of several other cancer vaccine players skyrocketing.

Antigenics Inc. garnered plenty of attention from analysts and doctors with a presentation showing that kidney cancer vaccine Oncophage (vitespen) reduced the risk of death by 46 percent (p = 0.036) in a follow-up subset analysis from its failed Phase III trial. The Phase III study missed its primary endpoint of improving progression-free survival and secondary endpoint of improving overall survival in adjuvant kidney cancer patients at risk for remission. (See BioWorld Today, March 27, 2006.)

Sunny Uberoi, a spokesperson for Antigenics, explained that the company had initially "assumed all patients in the adjuvant setting would be optimal because these patients were considered free of disease." But subsequent analyses indicated that the vaccine didn't work as well in patients at a high risk of disease recurrence. So Antigenics focused on analyzing and following the "intermediate risk" patients - about 60 percent of the overall trial population.

Data presented at ASCO represented an average of 4.5 years of follow-up on 604 patients. In the overall trial population, there have been 44 deaths in the Oncophage arm compared to 51 deaths in the control arm. But a subgroup of 362 intermediate-risk patients showed 18 deaths (9.8 percent) in the Oncophage arm compared to 32 deaths (18 percent) in the control arm (p = 0.036, HR = 0.54).

Ren Benjamin, analyst at Rodman & Renshaw, wrote in a research note that the "overall survival curves are consistent with the trends seen earlier for recurrence-free survival and support the idea that earlier-stage patients have more to gain from treatment with a cancer vaccine."

Oncophage is approved for intermediate-risk adjuvant kidney cancer in Russia, and the drug is under review by the European Medicines Agency with a decision expected by the end of the year. Uberoi noted that Antigenics has not yet submitted data to the FDA but may evaluate its options if Oncophage gains European approval. Yet the FDA is not fond of subgroup analyses or secondary endpoint data. The agency made Dendreon go back and run a confirmatory Phase III trial when it found itself in a similar situation. Uberoi said a confirmatory trial for Antigenics would take 10 years and cost $500 million. (See BioWorld Today, May 10, 2007, and April 29, 2009.)

The competitive treatment landscape also may present complications for Antigenics. Dendreon's Provenge was being studied in late-stage prostate cancer patients with no options except chemotherapy, and while there are no drugs approved specifically for adjuvant kidney cancer, there are late-stage treatment options like Nexavar (sorafenib, Onyx Pharmaceuticals Inc. and Bayer Pharmaceuticals Corp.) and Sutent (sunitinib, Pfizer Inc.). Shares of Lexington, Mass.-based Antigenics (NASDAQ:AGEN) rose 16 cents, or 22 percent, to close at 89 cents on Monday. Oncophage also is being studied in a Phase II brain cancer trial with data expected later this year.

Celldex Pops on Phase II GBM Data

Celldex Therapeutics Inc. and partner Pfizer Inc. presented updated data from two single-arm Phase II studies of cancer vaccine CDX-110 (PF-04948568) in newly diagnosed glioblastoma multiforme (GBM). In the first study, which included 18 patients receiving the vaccine as a monotherapy, median overall survival was 26 months and median time to progression was 14.2 months. In the second study, which included 22 patients receiving CDX-110 plus maintenance temozolomide, median time to progression was 15.2 months and overall survival was estimated to be 23.6 months. (See BioWorld Today, June 4, 2008). Shares of Celldex (NASDAQ:CLDX) gained $2.20, or 24.4 percent, to close at $11.22 on Monday.

Pfizer paid Celldex $50 million up front in a potential $440 million deal for rights to CDX-110 last year. The partners are planning a randomized Phase II trial for the drug, which targets epidermal growth factor receptor variant III, a mutated form of EGFR found in cancer cells. (See BioWorld Today, April 18, 2008.)

Biovest Shares Soar, but Questions Remain

Despite the fact that its parent company Accentia Biopharmaceuticals Inc. is in bankruptcy, Biovest International Inc. got a nice stock bump from its presentation of Phase III data with cancer vaccine BiovaxID (personalized anti-idiotype vaccine) in non-Hodgkin's lymphoma (NHL). Shares of Tampa, Fla.-based Biovest (Pink Sheets:BVTI) popped 39 cents, or 80 percent, to close at 88 cents on Monday. Biovest said patients who received BiovaxID in the Phase III NHL trial achieved median progression-free survival of 44.2 months compared to 30.6 months for those who received a control vaccine (p = 0.045). The risk of disease recurrence was 38 percent lower with BiovaxID. (See BioWorld Today, July 18, 2008.)

Yet analysts have raised doubts about how receptive the FDA will be to Biovest's analysis. Although the trial randomized 177 patients, the data presented include only 117 patients from a prospectively identified subset who maintained a complete response to chemotherapy for at least six months and who received active or control vaccine. Additionally, while a "p" value of less than 0.05 normally would be sufficient for statistical significance, the "p" value specified in Biovest's statistical analysis plan was 0.01.

In other ASCO cancer vaccine news:

• Generex Biotechnology Corp., of Worcester, Mass., presented data from a Phase I trial of AE37 showing the vaccine is well tolerated and induces immune responses in prostate cancer. A Phase II breast cancer study is ongoing. Shares of Generex (NASDAQ:GNBT) rose 6 cents, or 16 percent, to close at 43 cents on Monday.

• Oncothyreon Inc., of Seattle, and partner Merck KGaA, of Darmstadt, Germany, presented data showing that Stimuvax (BLP25 liposomal vaccine) was well-tolerated in non-small-cell lung cancer patients after up to eight years of follow-up from a Phase II trial. Merck is conducting a Phase III study. (See BioWorld Today, May 4, 2001.)

• Oxford BioMedica plc, of Oxford, UK, presented updated results from open-label trials of Trovac in colorectal and renal cancer. An analysis of four colorectal trials showed that 59 of 73 patients had an antibody response, which correlated to survival. An analysis of two renal cancer trials showed median progression-free survival of 3.6 months and overall survival of 13.2 months. TroVax targets the 5T4 tumor antigen; it also is being studied in a Phase III renal cancer trial. (See BioWorld Today, Oct. 8, 2008.)

Published  June 2, 2009