NEWS

License to Test Cancer Vaccines in U.S. a Victory for Cuban Biotechnology

Judith Randal

Although the International Symposia on Coma and Death, a quadrennial event in Havana since 1992, is always held during a U.S. presidential election year, American scientists and clinicians have always been able to attend—until this year. U.S. citizens must have a license from the Office of Foreign Assets Control (OFAC, a part of the Treasury Department) to legally travel to Cuba, and all of the Americans who had hoped to go to the March 2004 meeting had their applications turned down.

Despite that and further measures tightening the decades-old U.S. trade embargo against Cuba, CancerVax, a Carlsbad, Calif., biotechnology firm, fared better with the OFAC. It had long sought the agency's permission to license three experimental cancer vaccines from the Cuban research institute that developed and patented them, and permission was granted in July. Cuban president Fidel Castro himself was there when executives from CancerVax and officials of the Center for Molecular Biology (Spanish acronym CIM) signed the deal in Havana.

CancerVax became interested in these genetically engineered therapeutic vaccines when David F. Hale, its president and chief executive officer, ran across a poster from CIM researchers at the 2001 annual meeting of the American Society of Clinical Oncology. "Much of the focus at ASCO that year was on Imclone Systems' [then still investigational] monoclonal antibody [cetuximab, now marketed as Erbitux by Merck KGa in Europe and Bristol-Myers Squibb in the United States]... and its targeting of epidermal growth factor receptors," Hale recently recalled. "So when I saw this poster [about a novel approach to the EGF pathway], it stopped me in my tracks."



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David Hale

 

More serendipity followed, much of it because of Donald L. Morton, M.D., medical director and surgeon-in-chief at the John Wayne Cancer Institute in Santa Monica, Calif. While perhaps better known as the originator of the sentinel node concept, Morton also pioneered a therapeutic vaccine for melanoma during the 1960s, and when CancerVax was started in 2000, the firm's primary purpose was to ready his vaccine for commercialization. (It is now in phase III trials.)

In short, as an elder statesman of tumor immunology, he was well positioned to help the young company assess prospects for the Cuban vaccines. In addition, a CIM oncology vaccine researcher—Adriana Carr-Perez, Ph.D.—had been a visiting scientist at the John Wayne Cancer Institute, so Morton was somewhat familiar with CIM's work. He had also heard Tania Crombet-Ramos, M.D.,—also a CIM oncology vaccine researcher—speak at the 2001 ASCO meeting.

Still, it was a trip to Havana (with an OFAC permit) that really sold Morton on the professionalism of Cuban scientists. As he put it in a Congressional hearing upon his return home, "I was impressed by the depth and sophistication of their research, especially as it relates to tumor immunology."

That, of course, did not guarantee the success of CancerVax's quest to license the CIM vaccines. At one point, the Bush administration alleged that Cuba was using its research facilities to develop biological weapons, and, although the charge was never substantiated, it was also never retracted. In addition, Carr-Perez and Crombet-Ramos, key players in developing the vaccines, were caught up in the fallout. Until 2002, they had regularly gone to ASCO meetings, but they have been unable to get the requisite U.S. visas since then.

On the other hand, there was some bipartisan support in Congress for the permission CancerVax sought and a precedent for it as well. In 1999, the Clinton administration allowed SmithKlineBeecham (now GlaxoSmithKline) to license the world's only meningitis B vaccine from the Carlos J. Finlay Institute in Havana for eventual sale in the United States. (Although the vaccine is available in Latin America, it is still not available in the United States.)

Richard Popkin, a partner in the Washington law office of Swidler Berlin Shereff Friedman, played a major role in getting SmithKlineBeecham that license. As such, CancerVax sought his assistance.

Under the terms of the consequent agreement, CIM and the Castro government will earn no money from CancerVax until and unless one or more of the Cuban vaccines is approved by the U.S. Food and Drug Administration and is marketed in the United States. For now, payments—a total of $2 million a year—will be made in barter instead of cash. As Hale explained it, the Cubans will decide from a U.S.-approved list of food, medicines, and medical supplies which of them they want, and CancerVax will arrange for their delivery.

A Canadian venture capital firm based in Mississauga, Ontario, is also poised to profit. Formerly called York Medical, YM Biosciences partnered with CIM in 1995 to work toward commercializing the vaccines. Although YM had returned its interest in one of them to CIM by the time CancerVax entered the picture, it had kept its rights in the other two.

Accordingly, CancerVax will make so-called "milestone payments" to YM as studies move the two products closer to FDA approval and, should the vaccines be marketed, will pay YM royalties. The Bush administration has agreed to this arrangement.

The three Cuban vaccines are based on the idea that an excess of molecules in the EGF pathway fuels the growth and spread of many solid tumors. Ordinarily, a patient's immune system is blind to the excess because the body makes these EGF molecules anyway (albeit in smaller amounts). So the vaccines are designed to target one or another of them (there are several kinds) by coupling it to a foreign protein that the immune system will detect. In principle, an antibody response should follow that slows tumor growth.

Two of the vaccines, called SAI-TGF-alpha and SAI-EGFR-ECD, are still in preclinical development. But a third, SAI-EGF, has 5 years of phase I/II trials in advanced non–small-cell lung cancer (NSCLC) behind it. The trials have been done in Cuba, Canada, and England and have consistently shown the vaccine to be well tolerated. CancerVax's immediate plans for it include more extensive phase II trials in non–small-cell lung cancer—some of them, perhaps, in conjunction with chemotherapy.

Meanwhile, the question is whether the United States will see its way to clear other potential cancer treatments for testing in the United States.

"This is a unique case in that there is the potential to successfully treat a deadly disease using technology not otherwise available," U.S. State Department spokeswoman Darla Jordan said in July when CancerVax got its OFAC permit. But she added that "as a matter of policy, the United States will continue to consider license requests (involving Cuban products) when there is the potential to benefit public health."

Assuming that policy holds, the next logical candidate to fill that bill could well be TheraCIM, a humanized monoclonal antibody that is partly owned by YM and, as its name suggests, was created at CIM. Like Erbitux, TheraCIM targets EGF receptors on the surface of cancer cells to block tumor growth.

After showing early promise in combination with radiation therapy for inoperable head and neck cancers in several clinical trials, this drug is now under further study. A phase I/II trial of it for pediatric gliomas (a type of brain cancer) accrued its first patients in June. And both a phase III trial of TheraCIM for adult gliomas and a phase II trial for metastatic pancreatic cancer are now being launched under the auspices of CIM-YM's European licensee, a German firm called Oncoscience AG.

A further wrinkle is that the European Medicines Agency, a part of the European Union's regulatory structure, has assured Oncoscience that it can count on orphan drug status for TheraCIM if it is approved for the treatment of adult gliomas as the result of that phase III trial. That designation could give the German firm the exclusive right to sell the Cuban drug in the European Union's member countries for as long as a decade.

For previous articles on biotechnology in Cuba, see News, Vol. 92, No. 12, p. 962, and Vol. 92, No. 13, p. 1034.



             
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