By Jim Shrine
Oxigene Inc. discontinued development of its lead drug, Neu-Sensamide, because the radiation sensitizer in a Phase III study caused too many side effects to make it commercially viable.
The company, based in Stockholm, Sweden, and Boston, already has a next-generation product in Phase I trials, one it believes will be better than the first and second versions, Sensamide and Neu-Sensamide.
Those two drugs and the third-generation agent, Declopramide (formerly Oxi-104), are from a class of N-substituted benzamides that inhibit a DNA repair enzyme. They are designed to make cancer cells more sensitive to destruction by radiation and chemotherapy.
¿Of course, it¿s always a disappointment when you have to close development of a drug,¿ Oxigene President and CEO Bjorn Nordenvall told BioWorld Today. ¿However, our disappointment around Sensamide and Neu-Sensamide happened more than a year ago, when we identified significant problems with [central nervous system] side effects.
¿For me, it¿s a little bit of relief,¿ he continued. ¿Now, we can focus on drugs with better commercial potential, and we do it with good financial strength.¿
Oxigene had been in Phase III trials for about one year, testing Neu-Sensamide in combination with radiation therapy in patients with non-small-cell lung cancer. Nordenvall said about 25 percent of patients had dropped out of the study due to anxiety, depression, restlessness and similar central nervous system-related side effects.
Discontinuation of the study had nothing to do with the product¿s effectiveness, Nordenvall said, since it still is too early to gauge any effect on survival.
¿It is not about a lack of efficacy,¿ he said. ¿It¿s only because of the fact we have these side effects in a high percentage.¿
The product includes a highly concentrated formulation of the generic drug metoclopramide, which is known to cause such side effects. They result from binding to dopamine receptors in the brain, Nordenvall said. The company expected Neu-Sensamide to have addressed that problem much better than it did, he added.
Third-Generation Drug Initially Aimed At Colon Cancer
Declopramide, however, is a new chemical entity designed not to bind to dopamine receptors ¿ a quality documented in animals and patients, he said.
¿We feel we have eliminated the side effects with the third generation, Declopramide,¿ he said. ¿We are dosing patients significantly higher than the second generation. We see no side effects at all.¿
Initial studies of Declopramide are in combination with chemotherapeutics in colon cancer. Those studies should be completed by summer, Nordenvall said, with Phase II trials expected to get under way by the end of the year.
The news, while sending Oxigene¿s stock down, didn¿t cause the company to lose half its value or more, as has happened to several other biotechnology companies reporting failures of their lead drug candidates in recent months. Oxigene¿s shares (NASDAQ:OXGN) fell $1.125 Tuesday, or 12.5 percent, to close at $7.875.
Nordenvall said Oxigene will use the $6 million saved by stopping development of Neu-Sensamide to further three other drug candidates: Declopramide; Combrestatin A-4 Prodrug, an anti-tumor vascular targeting agent in three Phase I studies; and Cordycepin, a nucleoside analogue in Phase I trials in patients with acute lymphoblastic lymphoma.
¿We have $30 million in the bank today,¿ and the estimated annual burn rate of $10 million will fall because of stopping Neu-Sensamide development, Nordenvall said. ¿We will have all the money we need to develop the third generation [Declopramide] and the vascular targeting agent [Combrestatin], which we believe is at least as interesting as the third-generation product.
¿Our major aim this year,¿ he added, ¿is to sign the first major corporate deal around Combrestatin. We are in very serious discussions with leading companies in this sector. The second priority is to start discussions with the same companies around Declopramide when we finalize Phase I trials. We believe the commercial potential for those products is much better than the drug we are now closing.¿ n