By Randall Osborne

With plans to file a biologics license application (BLA) for its melanoma vaccine as a monotherapy later this year, Ribi ImmunoChem Research Inc. has sold worldwide marketing rights, except in Canada, to Schering-Plough Corp., in a deal valued at up to $30 million in signing fees and milestone payments.

The agreement could lead to Hamilton, Mont.-based Ribi making its vaccine, Melacine, available for use with Intron A (interferon alfa-2b), which already is marketed by Schering-Plough, of Madison, N.J.

Under terms of the agreement, Ribi gets an undisclosed signing fee plus milestone payments as Melacine gains marketing approvals in the U.S. and Europe. Ribi also will receive transfer payments for supplies of Melacine, and royalties on sales.

Biomira Inc., of Edmonton, Alberta, has licensed exclusive marketing rights for the vaccine in Canada.

Melacine consists of lysed, purified cells from two human melanoma cell lines with a broad array of melanoma antigens, combined with Ribi's proprietary Detox adjuvant, which contains monophosphoryl lipid A and mycobacterial wall skeleton to stimulate the immune system.

In a Phase III study, Ribi found Melacine improved the quality of life — though not survival — for Stage IV (metastasized) melanoma patients treated with the vaccine as compared with those treated with chemotherapy. (See BioWorld Today, May 21, 1997, p. 1.)

A subset analysis, however, showed an increase in median survival among those Melacine patients who exhibited clinical responses to the vaccine, said Kris Dyszynski, director of licensing activities for Ribi.

In the subset analysis, the median survival rate for those who responded was 18.2 months, compared with an 11-month median survival rate for all patients given Melacine. The rate for chemotherapy patients was 15.2 months for those who responded, compared with 12.4 months for all chemotherapy patients.

"We think that's very important," Dyszynski said. "Should the product be approved, patients are evaluated for clinical response 14 weeks after Melacine initiation. It's early enough that they can be switched to an alternative modality if they don't respond."

In a clinical research collaboration with Schering-Plough, Ribi is conducting a Phase III trial of Melacine with Schering-Plough's Intron A for Stage IV melanoma. That trial is expected to be analyzed late next year, with a potential filing for regulatory approval in mid-2000, which would trigger a milestone payment under the marketing deal.

"[Schering-Plough] is currently marketing Intron A for earlier-stage melanoma," Dyszynski said. "We believe the two products will complement each other, and this is the best possible marketing partner for Melacine."

In 1995, the FDA approved Intron A as an adjuvant treatment to surgery for melanoma patients with a risk for recurrence. (See BioWorld Today, Dec. 7, 1995, p. 1.)

Melacine also is being studied as a monotherapy in a Phase III trial with Stage II melanoma patients who have had primary tumors surgically removed. Data will be analyzed late this year. Assuming favorable results, regulatory submission would come in the middle of next year, triggering a milestone payment from Schering-Plough.

"There is a variety of other approaches, but Melacine is much farther along in development than any other melanoma vaccines," Dyszynski said. "All the other results that have been made public are Phase II results."

Avax Technologies Inc., of Kansas City, Mo., began a Phase III trial last fall of its M-Vax autologous cell vaccine, which works by conjugating the patient's tumor cells to a small molecule known as a hapten (dinitro phenyl). They are then injected back into the patient along with cyclophosphamide, an agent that boosts immune response and is commonly used in chemotherapy. (See BioWorld Today, Oct. 31, 1997, p. 1.)

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