Manufacturing Capability a Factor in Success of New Biologics

NEW YORK—Many biologic therapeutic manufacturers face “critical choke-points” in the future as they attempt to satisfy market demand, according to William R. Rohn, chief operating officer of IDEC Pharmaceuticals, the San Diego-based company that produces the anti-CD20 monoclonal antibody rituximab (Rituxan) in the United States.

Although Mr. Rohn sees no problem in satisfying future demand for Rituxan, his company is planning to build a new $300 to $400 million facility to fulfill the need for future products now in their pipeline. Zevalin (ibritumomab tiuxetan, IDEC-Y2B8), an investigational radio-immunotherapy in the late stages of development as a treatment for certain non-Hodgkin’s lymphomas, will continue to be manufactured in IDEC’s current FDA-licensed facility.

Speaking at an IDEC business presentation before market analysts and others, Mr. Rohn pointed out that biologic pharmaceuticals are often used to treat chronic diseases that may require dosing over long periods of time and, therefore, significant quantities of drug. “So clearly, being able to supply commercial markets is an important issue today,” he said.

There will be choke points, he said, because hundreds of biologics are under development, and there are potential limitations on market penetration due to a shortage of contract manufacturing capability to supply the product. In IDEC’s case, building a substantial manufacturing facility will help reduce the drug development cycle time, since it will relieve the company’s reliance on contract manufacturing schedules and availability.

Another way to reduce drug development time is to manage clinical trial data better, Mr. Rohn said. His company has invested in data management systems “to squeeze that process down,” he said. IDEC is going to electronic filings of its biologic license applications (BLAs) in an attempt to shorten the FDA review time.

The Rituxan BLA was about 46,000 pages in approximately 138 volumes, Mr. Rohn said, while the Zevalin BLA is about 94,000 pages in more than 300 volumes. But the text is all contained on 12 CD-roms. “This will be one of the first fully electronic BLAs submitted to the FDA, and the feedback we have gotten from the agency is that electronic submissions do indeed reduce review time,” he said.

Next month, at the American Society of Hematology (ASH) annual meeting, IDEC will present the final results of a phase III study comparing a standard course of rituximab as the control arm with a combination of rituximab plus Zevalin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Interim analysis data have already been presented showing an 80% response rate for the rituximab/Zevalin combination vs 44% for rituximab alone.

An Oncology Franchise

Mr. Rohn, whose company focuses on the development of targeted therapies for the treatment of cancer and autoimmune diseases, was asked what it takes to develop a successful “oncology franchise.”

He answered that “the company needs to offer itself as a good partner, one that is willing to share revenues or profits with other small biotechnology companies and not just take products in exchange for royalties.”

IDEC is open to revenue and profit sharing, he said. For example, the company entered into a collaborative agreement with Genentech in 1995 for the clinical development and commercialization of Rituxan.

Building an oncology franchise also means establishing marketing expertise. In oncology, Mr. Rohn explained, smaller drug companies can compete with bigger ones.

“Oncology is not a ‘brute force marketing’ therapeutic category. With a very small group of people, 70 to 100, you can canvass all of the decision-makers—the oncologists and hematologists—who manage patients with cancer in this country. So with a good commercial infrastructure, you can be very successful going head to head with Bristol-Myers, Upjohn, SmithKline-Beecham, etc.”

In the oncology market, success is determined by marketers who understand the nuances of the therapeutic category and can talk in the language of the key clinical decision-makers. “Ultimately, success in terms of having a long-term oncology business is based on developing more products faster,” he said.