BioWorld International Correspondent
PARIS - The Strasbourg-based gene therapy company Transgene SA is refocusing its clinical development program in light of the mixed interim results obtained from Phase II clinical trials of its two cancer vaccine candidates, while expanding ongoing Phase I trials of two immunotherapy products.
As CEO Jean-François Carmier explained, "Each of our four cancer product candidates has generated clinical data supporting further specific development. We intend to pursue the development of MVA-HPV-IL2 and Ad-IFNgin monotherapy settings for early stage diseases, and MVA-Muc1-IL2 and Ad-IL2 in combination with chemotherapy for advanced cancers."
The cancer vaccine MVA-Muc1-IL2, which uses the MVA vaccinia virus vector to express the Muc1 tumor-associated antigen found in most adenocarcinomas, is being evaluated in four Phase II clinical trials to assess different doses (breast cancer), dosing schedules (prostate cancer) and treatment modalities, such as in combination with standard chemotherapy (lung cancer), and in combination with standard immunotherapy (renal cell carcinoma).
The lung cancer trial, being tested on patients suffering from advanced non-small-cell lung cancer, yielded a favorable rate of clinical response when used in combination with standard chemotherapy, both complete and partial. As a result, Transgene said it will continue with the second stage of the trial, which is expected to be completed in the first half of 2004.
In the breast cancer trial, on the other hand, the clinical response was not deemed sufficient to proceed to the second phase. Meanwhile, patients are being enrolled for trials of MVA-Muc1-IL2 in prostate and kidney cancer, with enrollment expected to be completed by the end of 2003.
A second cancer vaccine candidate, MVA-HPV-IL2, which uses the MVA vector to express the E6 and E7 antigens of human papillomavirus 16, an agent causally linked to cancer and precancerous lesions of the cervix, is being evaluated in three Phase II clinical trials.
One trial testing the product in stage 2-3 cervical intra-epithelial neoplasia yielded promising data on the first 15 patients in terms of clinical and histological responses and viral clearance. Final results are expected by year-end. Interim results from a trial involving women with HPV 16 cervical cancer resistant to, or recurrent after, radiotherapy did not produce a sufficiently positive clinical response for monotherapy to be pursued. Meanwhile, patients are being enrolled for a trial of MVA-HPV-IL2 in the indication of vulvar intra-epithelial neoplasia.
Transgene's two immunotherapy product candidates, Ad-IFNg and Ad-IL2, are based on its improved adenoviral vector and carry the interleukin-2 gene and the interferon gamma gene, respectively. Two Phase I trials - the first in the indication of cutaneous lymphoma and the second for the treatment of metastatic melanoma and other solid tumors - showed positive results in terms of efficient gene transfer and cytokine expression, with excellent tolerance up to the highest dose.
On the strength of those results, the trials are being extended into a Phase I/II phase. Transgene's medical and regulatory affairs director, Patrick Squiban, said 10 more patients are being enrolled for the Ad-IFNg trial in addition to the nine who participated in the original trial, while for Ad-IL2 another 12 patients are being added to the 20 original ones. In the new trials, the treatment period is to be extended (up to 12 months) and patients will be monitored up to time to relapse.
Moreover, since one of the virtues of these therapies is that they can be used to treat several tumors at once, Squiban said that up to three tumors will be injected simultaneously in the next trials. In the new patients, the two products also are to be tested in combination with chemotherapy.
Transgene's future plans call for Ad-IL2 to be tested in the indication of soft tissue sarcomas and renal cancer and Ad-IFNg in cellular hepato-carcinoma. A Phase II trial of Ad-IFNg in this indication is due to start in China in the third quarter. The company has applied for orphan drug status for that product in Europe and is planning to file a similar application in the U.S.
Transgene has a fifth product in clinical development, which is a gene therapy for Duchenne's disease, a form of muscular dystrophy. A Phase I trial that started in September 2000 was completed in December, with no adverse events recorded. A shorter Phase I trial is planned to test intra-arterial administration of the therapy. The program is being entirely financed by the French Muscular Dystrophy Association under an agreement for it to provide Transgene with funding of €4 million over the three years from mid-2001 to mid-2004.
Transgene's strategy is to negotiate co-development agreements for taking products into Phase III and beyond. "Phase III trials will cost millions and millions of euros and there is no question of Transgene doing that by itself," Carmier said.