BioWorld International Correspondent
LONDON - Maxim Pharmaceuticals Inc. became the first to make an all-electronic submission in Europe last week, when it filed for Ceplene in combination with interleukin-2 for the treatment of advanced malignant melanoma.
Larry Stambaugh, Maxim CEO, said: "Pieces of [marketing authorization applications] have been made by various companies electronically, but nobody has put an all-electronic submission together before. This is a wave of the future, and it is a very, very, positive move."
The European Agency for the Evaluation of Medicinal Products (EMEA) asked San Diego-based Maxim to pilot an all-electronic submission, and Stambaugh said the company has worked closely with the agency to achieve the milestone.
The Ceplene (histamine dihydrochloride) application is being filed as an Electronic Common Technical Dossier, an international standard that the EMEA formally agreed to in July.
But Stambaugh said the move to electronic submission had not made filing any less onerous, in this case.
"We still had to file paper as well, but when [the process] is fully electronic, it will be different," he said.
EMEA has not given Maxim any sign that the electronic submission will speed the review process. However, reviewers will have the option of viewing the dossier online.
"At this stage, I think the great benefit will come when there are references to data, publications, or tables elsewhere, and you can easily jump from section to section," Stambaugh said.
The paper file for Ceplene runs to 146 volumes, each about five inches thick. "I don't know how many pages that is, but it is a lot," he said. "[The paper version] is very, very cumbersome, and it is difficult to look up cross references, compared to being on the website."
Ceplene was ruled not approvable by the FDA in January 2001. The European application is based on the same Phase III trial, but Stambaugh said the data has now matured, with 36-month follow-up data showing statistically significant improvements in survival rates.
Two-year survival rates for patients with liver metastases were 18.2 percent for the group treated with Ceplene and IL-2, vs. 2.7 percent for the group treated with IL-2 alone.
Also, a Phase II trial reported earlier this year confirmed the survival advantage.
"We discussed this with the EMEA, and the conclusion was the data could be sufficient in Europe," Stambaugh said.
If approved, Ceplene will be the first treatment for advanced malignant melanoma. Melanoma is reported to be the fastest-growing cancer in the developed world, with an estimated 200,000 cases diagnosed in the U.S. and 150,000 in Europe in 2002.
Maxim has begun the search for a European marketing partner. The company held a seminar in Copenhagen a few weeks ago, which was attended by 17 pharmaceutical companies. "We are now in the process of following up individually, and I will be making visits to some companies this week, " Stambaugh said.
Maxim intends to market the product itself in the U.S. It has just reached the stage of fully enrolling a second Phase III trial to support an amended new drug application.
However, the company will not be able to draw on the electronic EMEA filing when it resubmits Ceplene to the FDA.
"We have an initial FDA filing under an old format, and we will have to stay in that format," Stambaugh said.
Companies and regulators are just beginning to appreciate the advantages that electronic submissions will bring, Stambaugh said. In the future, all communication, beginning with submitting the investigational new drug application, will be electronic, and companies will keep adding to the file as products progress in the clinic.
"Making the first all-electronic submission is an important milestone, but we are just at the beginning, and there will be some pain in the transition," Stambaugh said.