[Updated: 2:30 pm Pacific] ZymoGenetics just can’t seem to catch a break.
The Seattle-based biotech company has some positive, albeit preliminary, data out today on its experimental treatment for melanoma that has spread throughout the body—one of the toughest forms of cancer to treat. But ZymoGenetics (NASDAQ: ZGEN) had the misfortune to be upstaged big-time by Bristol-Myers Squibb, which dominated the news with its promising results for a melanoma drug called ipilimumab, or “ipi” for short. One researcher at the American Society of Clinical Oncology, quoted in the New York Times, said the Bristol drug was a “historic” advance. The detailed results were published online today in the New England Journal of Medicine.
Any drug with promise against melanoma that has spread, or metastatic melanoma, to use the clinical term, is bound to be big news. This is a relatively rare form of skin cancer that is diagnosed in about 68,000 people in the U.S. each year—but it kills an estimated 8,600 people a year nationwide, according to the American Cancer Society. The most commonly used drug, a chemotherapy called dacarbazine or DTIC, has historically only helped shrink tumors in about 15 percent of patients, and only keeps them from spreading for a median time of about six weeks.
The ZymoGenetics product, called IL-21, is designed to work differently, as a genetically engineered protein drug that stimulates a variety of cells from the immune system to attack the cancer. The drug showed in a mid-stage trial of 40 patients that it could at least partially shrink tumors about 23 percent of the time, and keep the cancer from spreading for a median period of 4.3 months. This study didn’t randomly assign patients to the Zymo drug or a comparison group, so it’s impossible to say for sure how much of an advantage the new drug might offer. But patients are being followed up to measure survival times, ZymoGenetics said.
Still, the lead researcher on the study, Teresa Petrella, had an optimistic comment to make today in a ZymoGenetics statement. The results are good enough for researchers to take the next step, and push IL-21 along to the next phase of more rigorous study, she said.
“The progression-free survival and response rate with IL-21 in patients with advanced melanoma are promising and warrant further investigation,” said Petrella, a researcher with the National Cancer Institute of Canada’s Clinical Trials Group. “Metastatic melanoma is difficult to treat and has no effective standard of care. We look forward to extending these observations in a randomized Phase 2 study.”
Intriguing as the ZymoGenetics results are, they didn’t measure the drug’s ability to prolong life—the gold standard measurement for cancer drugs. That’s what got researchers so pumped about Bristol-Myers’ ipilimumab. The study of 676 patients found that those who got the Bristol treatment lived a median time of about 10 months, compared with 6.4 months for those in a control group. After two years, about one out of four people who got the drug (23 percent) were alive, compared with one out of seven (14 percent) on the comparison treatment.
With that said, here’s what ZymoGenetics and its collaborators learned about IL-21. Patients got one of three different doses through a daily intravenous injection, although they had periods in which they could go off the drug. The most common side effects were fatigue, rash, and fever.
Researchers saw more serious side effects in patients on a high dose. Four out of 10 patients who got a dose of 50 micrograms per kilogram of body weight ended up with a serious rash, termed as “grade 3″ on a scale of 1 to 4, with four being the most severe. Only three of 30 patients on the lower, 30 microgram dose, had that same kind of serious rash, researchers said. A total of nine serious adverse events were reported—including one patient who had a severe depletion of white blood cells and suffered an infection, and two patients who had significant elevation of liver enzymes in the blood, which can be a sign of liver damage.
Based on the findings, researchers are planning to go forward with the lower of the two doses, Petrella said in a statement.
[Updated with comments from Eleanor Ramos, ZymoGenetics’ chief medical officer.] ZymoGenetics’ next clinical trial will randomly assign about 80 patients to its new drug or DTIC, says Eleanor Ramos, the company’s chief medical officer. The trial is on track to start within a couple months. And it should offer an alternative to the Bristol drug, because that product was tested as a second-round therapy for melanoma patients, while the ZymoGenetics drug is a first-round therapy for patients with the worst prognosis, Stage 4 disease, she says.
“Clearly, not every patient responds to the other therapies,” Ramos says. “And a 23 percent response rate is quite good in this patient population, with a single-agent treatment, and with the safety profile we have. There’s room for different therapies, and different combinations.” She added that the ZymoGenetics drug could be combined over time with oral pills in cocktail treatments that may be able to boost the tumor shrinkage rates.
The ZymoGenetics data being presented today is encouraging, says David Miller, an analyst with Seattle-based Biotech Stock Research. But clinical trial plan might need to be re-assessed based on the changing competitive landscape with Bristol-Myers.
“The data look good in this patient population, though ZymoGenetics did exclude patients with larger lesions,” Miller says. “A Phase 2b trial against DTIC might not be the right trial given the ipi data.”
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