2 Biotech Firms in Race to Market High-Precision Lymphoma Drugs
Imagine an anti-cancer drug that acts like a guided missile, seeking out a patient’s malignant cells and then destroying them with microscopic radioactive warheads, while sparing the surrounding healthy tissue.
Such an approach to battling cancer was first envisioned a quarter of a century ago with the discovery of a way to make large amounts of highly specific antibodies, natural substances that travel through the bloodstream and can seek out targets on the surface of tumors.
It seemed a simple matter to attach atoms of radioactive isotopes or toxins to the antibodies and create potent tumor killers, but the dream of using antibodies to deliver a radioactive particle to a tumor has proved elusive.
Now, however, two California biotechnology companies are racing to get the first such drug to market for the treatment of non-Hodgkin’s lymphoma, a surprisingly common form of cancer.
If they are successful--and early results show that both will be--they will usher in a new era in cancer treatment, eventually replacing radiation and chemotherapy in at least some cases with a more efficient approach that kills tumors but minimizes side effects.
One of those companies, Coulter Pharmaceutical Inc. of South San Francisco, once held a commanding lead in this biotechnology arms race, only to suffer a setback in August when the Food and Drug Administration asked for the company to resubmit data from crucial clinical trials of its atomic antibody, Bexxar.
The company’s shares fell off immediately and have lost about 50% of their value, closing Friday at $16.56 on Nasdaq.
Coulter’s stumble has allowed IDEC Pharmaceuticals Corp. of San Diego to close the gap, and IDEC officials think they have a chance next year to get their drug, Zevalin, before the FDA for review within a few months of Coulter’s Bexxar, if not at the same time.
“Six months ago, we were about 12 months behind,” said IDEC’s chairman and chief executive, William H. Rastetter. “It would appear we are maybe three months behind now.”
And that deficit could vanish, he said, if the FDA decides to take both drugs to its advisory committee at the same time, allowing “a side-by-side comparison.”
Coulter’s executives declined to comment, but a spokeswoman acknowledged the sense of competition and expressed confidence that Coulter’s antibody would be superior to IDEC’s.
The company and its partner in developing Bexxar, pharmaceutical giant SmithKline Beecham, announced in the summer that the FDA asked that Coulter resubmit the results of its Bexxar trials in a different computerized format but that the agency was not requiring any additional tests of the experimental drug in patients.
Coulter was spun off from a company now known as Beckman Coulter in 1995, specifically to develop Bexxar. The company, which has 200 employees, reported a net loss of $11.3 million in the third quarter as it beefed up its sales force operation and prepared to bring Bexxar to market. It has reported no revenue yet.
IDEC’s Rastetter said he has called for a head-to-head test of the two drugs, which are similar in approach but still distinctly different compounds and could have different effects, but he acknowledges that’s unlikely to happen any time soon.
A summary of IDEC’s results in advanced-lymphoma patients--individuals whose tumors don’t respond to standard treatment--was published last week. It showed that 80% of those who received IDEC’s experimental drug along with Rituxan, IDEC’s FDA-approved nonradioactive antibody treatment, showed improvement, compared with 44% of those patients receiving Rituxan alone.
IDEC’s share price rose sharply on Nasdaq to end the week at $125 after release of the summary.
Coulter, which like IDEC tested its drug at university cancer centers, also reported positive results for its drug. More than half of 49 patients with advanced cases of lymphoma showed improvement following treatment with Bexxar, and a third of the patients went into complete remission.
But the summaries made available by the American Society of Hematology do not allow easy comparisons of the two drugs. Scientists who tested one or the other of the drugs will make more complete and updated reports on their results at the society’s annual meeting next month.
Both companies boast of the advantages of their different approaches. Coulter attaches radioactive iodine to its antibody; IDEC uses a radioactive form of the metal yttrium. There are differences in how the drugs are administered--patients who receive Bexxar will have to be isolated in many cases, even hospitalized briefly; patients getting Zevalin generally will not have to be.
But for patients in the late, desperate stages of the disease, what matters most is which one works best. And it is possible that each drug will find its own niche.
Analysts agree that there may be room for both Zevalin and Bexxar in extending life for advanced lymphoma patients. But it is the FDA that will decide which of the drugs gets to market first--or if the drugs get to market at all.
The drugs could establish either company as a pioneer in developing this new class of drugs, so long in development.
IDEC was the first company to have a cancer-fighting antibody on the market--one without an attached radioactive isotope. The drug Rituxan is fast becoming standard treatment for certain lymphoma patients.
It’s proved a financial success as well, boosting revenues for IDEC and its partner, Genentech, and adding IDEC to the ranks of the few independent biotech companies that are making a profit.
IDEC was founded in 1986 and went public five years later. It now has 400 employees and reported net income of $10.7 million last quarter on revenue of $30 million.
Rastetter realizes there could be an advantage to winning approval ahead of Coulter but that any lead could be only temporary.
“At this point, either one could get to market first,” he said. “It is a horse race. I think ultimately that doctors are going to pick the agent that is easier to use and that has the best safety profile for patients and for themselves.”
In 1975, two European scientists, Georges J.F. Kohler and Cesar Milstein, reported that they had found a way to use antibody-producing cells with tumor cells. The resulting cells were called “hybridomas”--immortal cells that could produce unlimited amounts of highly specific antibodies. For the discovery, which they shared freely with other scientists and did not patent, they received the 1984 Nobel Prize in medicine.
Despite the initial excitement about using antibodies as medicines, there were unforeseen difficulties. The antibodies were from mouse cells, and the human body rejected them as foreign. And it was difficult to obtain enough of an antibody to have a meaningful effect. For decades there was “a litany of negative results,” recalled Dr. Antonio J. Grillo-Lopez, IDEC’s chief medical officer.
But slowly, scientists learned to grow pure antibodies in large quantities in hamster tumor cells and, when necessary, to “humanize” them--to make them chemically similar enough to human antibodies that the body would not reject them.
Today, IDEC’s manufacturing facility can produce these purified antibodies by the pound instead of by the fraction of an ounce.
The technique led to Rituxan, which was approved by the FDA in late 1997. IDEC has been profitable every quarter since. The drug is intended for patients with non-Hodgkin’s lymphoma who are relapsed or whose tumor does not respond to conventional therapy. But as the disease progresses, the cycles between treatment and relapse shorten and patients soon run out of options.
Zevalin and Bexxar are aimed at these advanced cancers.
About 300,000 Americans suffer from non-Hodgkin’s lymphoma, a cancer of the immune system that affects a certain class of white blood cells. It is the sixth-leading cause of cancer death in the U.S., and as the population ages, the number of cases is rising quickly.
Analysts agree that the new radioactive therapies will not replace IDEC’s Rituxan but will supplement it.
“If people think a radioactive antibody will replace Rituxan, they are sorely misguided,” said Hambrecht & Quist analyst Richard A. van den Broek. With the new products, “you would expect higher efficacy, but also higher toxicity and also greater complexity in ease of use,” he said.
