By Jennifer Van Brunt
The excitement at this year's annual meeting of the American Society of Clinical Oncology (ASCO) must have been palpable. Report after report crossed the news wires and hit the morning editions of national newspapers about new results in cancer therapy emanating from the meeting's Los Angeles venue. For biotechnology companies, this event was especially meaningful: For the first time, the experimental results coming from biologically based therapies and potential vaccines were center stage.
The biotech industry's first public company stood squarely in the spotlight at the beginning of the week. Research physicians, oncologists and other attendees apparently packed the lecture hall when the final Phase III clinical trial results of Genentech Inc.'s humanized monoclonal antibody for treating metastatic breast cancer were presented May 17. The antibody, named Herceptin (trastuzumab), targets breast cancer cells that overexpress the growth factor receptor HER2; these cancers, which occur in about one-third of all cases, are particularly aggressive in nature.
The results showed that when the monoclonal antibody is used in combination with chemotherapy, it not only slows the progression of the cancer, but increases tumor shrinkage. Even when the antibody was given as a monotherapy to patients who had relapsed after one or two chemotherapy cycles, it was able to elicit an overall response rate of 16 percent, with 4 percent of those women experiencing a complete response.
Genentech already has submitted a biologics license application (BLA) to the FDA for Herceptin, which the agency has designated a fast-track product. This means it could be approved within six months once the FDA has accepted the BLA as complete for filing.
This exceptionally positive news gave a nice boost to Genentech's stock (NYSE:GNE), which gained 3.4 percent on May 18 to close at $72.375. If that doesn't look like much of a response on the part of investors — and compared to many other biotech stocks, the reaction was, to say the least, modest — one has to remember that Genentech's stock has a ceiling of $82.50 and a floor of $60.00. As part of Genentech's May 1995 revised agreement with majority owner Roche Holding Ltd., of Switzerland, the pharmaceutical giant has until June 30, 1999, to exercise its buyout option at a price escalating from $61.25 per share to $82.50. If Roche doesn't exercise this option, Genentech stockholders can sell their shares to Roche for $60.00 each. With little room to move, then, the stock normally responds only slightly to news — good or bad. Still, it's up 19.4 percent year-to-date, having closed 1997 at $60.625 per share.
If the clinical results on Herceptin titillated investors, then they lit a fire under the conference attendees. "The reception to the Genentech data by the oncology community was overwhelming," explained Samuel Waksal, president and CEO of New York-based ImClone Systems Inc. "For the first time, the oncologists are seeing that there's a future for the combination of biologics and chemotherapy, in doses that can be tolerated . . . and that the outcome is good for the patient." Waksal, whose own company is also developing biologically based cancer therapies, added that "biologics are really going to change cancer therapy."
Waksal has every reason to be enthusiastic, for ImClone Systems (NASDAQ:IMCL) also is developing a cancer therapy based on a monoclonal antibody that targets a growth factor receptor. This product, C225, is a chimeric monoclonal antibody that blocks the epidermal growth factor receptor (EGFr) associated with cancers of the head and neck and kidney, among others. And the product also is being studied in combination with standard cancer therapy. In data from Phase Ib/IIa clinical trials in head and neck cancer presented at ASCO, the researchers reported that C225 treatment together with radiation therapy was able to elicit a major response rate of 100 percent in all 12 evaluable patients. According to the literature, the major (complete or partial) response rate due to radiotherapy alone is 30 to 40 percent. ImClone's also testing the combination of C225 and platinum, Waksal said.
Many biotech companies developing various cancer therapies and vaccines are aiming at head and neck cancer. According to Waksal, there are several reasons why this particular type of cancer makes a compelling target. For one thing, it has a poor prognosis; patients relapse and die, even after treatments with chemotherapy and radiation. "Head and neck cancer needs new therapies," he said. As well, the cancer can be seen, it's accessible and can thus be injected directly with a drug, it's radiation-sensitive and it can be treated before it metastasizes.
Given data like these — early as they are — it's no surprise that ImClone Systems plans to bring the head and neck cancer trials forward to Phase III. The company also is conducting a Phase II/III trial of C225 (as a monotherapy) in patients with metastatic renal cell carcinoma.
ImClone's other major approach to treating cancer is through the use of vaccines, which in general are intended to stimulate the patient's own immune system to attack the murderous cells that are growing within. ImClone's drug candidate BEC2 is a genetically engineered molecule — an anti-idiotypic monoclonal antibody — designed to mimic the shape of the structural tumor antigen GD3, which is overexpressed on small cell lung carcinoma, melanoma and various soft-tissue sarcomas.
ImClone and its corporate collaborator Merck KGaA presented data at the ASCO meeting from a pilot study on BEC2 treatment of 15 patients with small cell lung cancer. Encouraged by the results, which demonstrated that BEC2 significantly increased survival for this patient population, the collaborators also announced that they have just started international Phase III trials of the vaccine. Merck KGaA, which is located in Darmstadt, Germany, is footing the bill for the clinical trials and is responsible for clinical development outside the United States.
Again, ImClone is not alone in its attempts to refine this tactic. In fact, there is more effort expended by the biotech sector to develop new therapies for treating cancer than in any other broad disease category. According to the Spring 1998 edition of the BioWorld Phase III Report, for instance, there are currently 89 late-stage clinical trials (out of a total of 231) being conducted on new treatments for cancer.
And according to the Washington-based Pharmaceutical Research and Manufacturers of America's latest report on biotech drugs in development, issued in March 1998, nearly half the drugs in all phases of development (151 out of 350 in the survey) are meant to fight cancer. That's way and above the next most frequent disease category, which is infectious diseases (with 36 products).
Many of those same cancer vaccines and monoclonal antibody-based therapies were also featured in presentations at ASCO last week. They are too numerous to summarize here, but synopses of the many clinical trial results can be found in the May 19, May 20 and May 21 issues of BioWorld Today.
The take-home message, according to ImClone's Waksal, is this: With the advent of biologically based therapies, whose side effect profiles are often tolerable (especially compared to heavy-dose radiation or chemotherapy), cancer will become a chronic, treatable disease — although not necessarily curable. Biologics will forever change the way we treat cancer, he said.