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New Prostate Cancer Drugs
  Bayer/Algeta's prostate 'alpha-pharmaceutical' improves survival
World News | June 06, 2011
Kevin Grogan
Bayer and Norwegian partner Algeta are celebrating after a late-stage trial of their prostate cancer drug Alpharadin was stopped early due to impressive overall survival data.
Bayer says the Phase III trial evaluating Alpharadin, the first in a new class of 'alpha-pharmaceuticals' which is based on radium-223, in patients with castration-resistant prostate cancer and symptomatic bone metastases met its primary endpoint by significantly improving overall survival - 14.0 months versus 11.2 months for placebo. The complete results from the study, which also revealed that the safety and tolerability of Alpharadin were consistent with previous Phase I and II findings, will be presented at an upcoming scientific meeting.
Based on a recommendation from the independent data monitoring committee, the study will be stopped and patients on the placebo arm will be offered treatment with Alpharadin. Noting that around 90% of men with advanced prostate cancer have bone metastases, "the main cause of disability and death in this disease," Chris Parker of the Institute of Cancer Research and Royal Marsden Hospital (and principal investigator for the trial), noted that the disease has a poor prognosis and treatment options are limited.
He added that based on the "observed survival benefit and its safety profile, Alpharadin may become an important treatment". The drug was expected to be submitted to regulators next year but Bayer said it is evaluating the filing strategy for the treatment based on the IDMC's recommendation.
Investors in Algeta, a Norwegian biotech, are particularly pleased with the news and its shares shot up this morning. At about 9.35 am (UK time), they were worth 54 Norwegian kroner, up 37%.
Study Shows Benefit of J&J Prostate Cancer Drug
CHICAGO--Johnson & Johnson's prostate cancer drug Zytiga showed a slightly improved survival benefit in updated data from a late-stage study that also revealed the potential for a new way to measure the common disease.
The data, presented at the annual meeting of the American Society of Clinical Oncology, reveal that measuring circulating tumor cells--cancer cells that have fallen off a tumor into the bloodstream--correlates with patient survival. The measuring of such cells could effect the development of future medicines because it may be used instead of measuring overall patient survival in a clinical trial, making such studies shorter, smaller and cheaper.
In the study, the median overall survival of patient on Zytiga rose to 4.6 months, compared to the previously reported benefit of 3.9 months. The measurement came after 20.2 months on treatment, showing that patients on the drug lived for 15.8 months compared to 11.2 months on a placebo.
Zytiga targets a protein that plays an important role in the production of testosterone, which stimulates cancer cells to continue growing.
The drug received Food and Drug Administration approval in April in combination with prednisone for patients with a certain type of late-stage prostate cancer previously treated with chemotherapy. The drug was given a shorten review and the decision came ahead of its June 20 regulatory goal date.
Prostate cancer is very common in older men, who are screened with a test for prostate-specific antigen, or PSA. But that measure can be deceiving, sometimes rising even when a patient is benefiting from a treatment, and vice versa, according to Howard Scher, chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center in New York.
The Zytiga trial found that measuring the circulating cells predicted a better prognosis and improved survival as early as four weeks after taking the drug.
The measurement of the cells in relation to patient survival was part of a formal collaboration with the FDA. The cells represent about one cell in a billion in the blood stream, according Dr. Scher.
While the data are encouraging, Dr. Scher said the finding will be tested in subsequent studies that may eventually determine if the measure could help guide treatment decisions for individual patients.
J&J's Prostate Drug Extends Life as Spur to $5 Billion Market
By Rob Waters - Jun 2, 2011
June 2 (Bloomberg) -- Bloomberg's Shannon Pettypiece reports on Johnson & Johnson's Zytiga, the first prostate cancer pill to win U.S. marketing approval in a family of treatments that offer new ways to stymie the male hormones that fuel tumor growth. Similar medicines from Medivation Inc. and Takeda Pharmaceutical Co. will report study results this weekend at the American Society of Clinical Oncology meeting in Chicago. Pettypiece speaks with Betty Liu on Bloomberg Television's "In the Loop." (Source: Bloomberg)
Dennis Prestholdt credits the past three years of his life to Johnson & Johnson (JNJ)'s Zytiga, the first prostate cancer pill to win U.S. marketing approval in a family of treatments that offer new ways to stymie the male hormones that fuel tumor growth.
Prestholdt, 67, a retired engineer at Honeywell International Inc., began taking Zytiga in 2008 as part of a clinical trial. On April 28, the drug was cleared for sale and, within five years, may generate $2.1 billion a year, said Jami Rubin, a Goldman Sachs Group Inc. analyst in New York.
The J&J drug may be a harbinger, said Eric Schmidt, a Cowen & Co. analyst. Similar medicines from Medivation Inc. (MDVN) and Takeda Pharmaceutical Co. will report study results this weekend at the American Society of Clinical Oncology meeting in Chicago. If approved, they would combine with Zytiga and other treatments to boost the market for prostate cancer therapies to $5 billion by 2015 from less than $1 billion now, Schmidt said.
"It's stunning how much innovation has taken place in the last five to six years," Schmidt said in a telephone interview. "It is never a great time to be a prostate cancer patient, but it sure beats a few years ago when the pipeline was barren."
While these drugs don't cure the disease, the therapies give doctors options to help patients live longer, said Charles Ryan, a medical oncologist and prostate cancer researcher at the University of California, San Francisco.
Tripling Survival Time
"If you go back to 1985 and ask what happened to a guy with advanced prostate cancer who went on hormone therapy, the answer is he lived about 12 months," said Ryan, who is treating Prestholdt. Using treatments approved in the past year, "you can probably triple that," he said in an interview.
Medivation's drug, called MDV3100, "has the potential to really add to the mix," Ryan said.
The medicine from the San Francisco-based company, developed with Astellas Pharma Inc. (4503) of Tokyo, may win U.S. approval by 2013 and reach annual sales of $1.7 billion by 2017, said Howard Liang, a Leerink Swann & Co. analyst in Boston.
The Millennium unit of Osaka, Japan-based Takeda is testing TAK700, a product similar to Zytiga, in late-stage trials that may be completed by 2013 or 2014, Nancy Simonian, Millenium's chief medical officer, said in a telephone interview.
About 218,000 U.S. men are diagnosed with prostate cancer and 32,000 die each year from the disease, according to the American Cancer Society. If a tumor is confined to the prostate, the walnut-sized gland between the bladder and urethra, patients may seek surgery or radiation to eliminate it. Or they may do nothing because a slow-growing prostate tumor may not alter an older man's life expectancy.
Cancer Spread
In about 15 percent of men with prostate tumors, the cancer will spread, according to the National Cancer Institute. For these patients, no cure exists. Treatments aim to keep the testicles from producing testosterone and other male hormones known as androgens, which prostate cancer cells use to grow.
One way is to surgically remove the testicles. Another treatment is a form of chemical castration called androgen deprivation using drugs such as Abbott Laboratories' Lupron or AstraZeneca Plc's Casodex.
These drugs "always work, but over time the treatment fails, usually after two years or sometimes longer," said Matthew Smith, an oncologist and prostate cancer specialist at Harvard Medical School in Boston.
The effort to block testosterone fails when the adrenal gland or the tumor begins making small amounts of androgen that kick-start new cancer growth, Ryan said. In the past, there was no way to stop that androgen.
New Theory
Zytiga from New Brunswick, New Jersey-based J&J changed the thinking by targeting an enzyme called CYP17 that helps make androgens outside the testicles. Stop it and you cut off a tumor's androgen "fuel supply," Ryan said.
Hormone therapy kept Prestholdt's illness in check for 10 years before his levels of PSA, a protein associated with prostate cancer, began to climb, signaling the disease was again on the march. He conducted research on the Internet and learned about Ryan's clinical trial of Zytiga, then known as abiraterone acetate. He e-mailed the doctor, visited, and in early 2008 began taking the pill as part of the study.
Given to patients with advanced prostate cancer who had stopped responding to standard hormone treatments and chemotherapy, Zytiga boosted survival from 11 months to 15 months, a study found.
PSA Levels Plunge
Prestholdt and patients in a smaller trial received the pill before getting chemotherapy and many got more benefit. Within two months of starting treatment, Prestholdt's PSA level plunged to zero, where it remains 40 months later, Ryan said.
Medivation's drug was discovered by researcher Charles Sawyers at the University of California, Los Angeles. He found what he calls the chief culprit in prostate cancer -- proteins known as androgen receptors that sit on the surface of tumor cells and act to switch on cancer-promoting processes.
"The androgen receptor is the business end of this whole pathway," Sawyers, who now works at Memorial Sloan-Kettering Cancer Center in New York, said in a telephone interview. "It's an oncogene" -- a cancer-promoting gene -- "for prostate cancer that turns on a whole repertoire of other genes."
Sawyers and his team looked for a compound to block the receptor. The result was the drug now known as MDV3100. Sawyers told David Hung, Medivation's chief executive officer and an old medical school classmate, about his findings, and Hung licensed the rights and put the medicine into clinical trials.
Early Studies
An early stage trial of 140 men showed that after 12 weeks on the drug, PSA levels were cut in half in 62 percent of those who hadn't been treated with chemotherapy and 51 percent of those who had, according to a company presentation in April. Takeda's experimental medicine reduced PSA levels by half or more in as many as 63 percent of 96 men who hadn't previously received chemotherapy, according to an early study to be presented at the cancer meeting.
MDV3100 acts on the most important driver of prostate cancer growth, while Zytiga exercises an indirect effect, knocking down testosterone levels to keep the androgen receptor from turning on, Hung and Sawyers said. Having multiple treatments may provide alternatives when tumors become resistant to one drug and stop responding, Ryan said.
"If you have drugs that work on different mechanisms, you can go from mechanism A to B to C and hit the cancer at three different weak points, from different angles," Ryan said.
J&J's drug may boost blood pressure, lower potassium and increase fluid retention, raising the risk of heart disease. To reduce these risks, patients take it with steroids.
Prestholdt also manages side effects such as fatigue and regular hot flashes normally associated with female menopause. A thick, absorbent T-shirt and a sense of humor help, he said. So does staying active.
"I'm basically enjoying my life at this point and hoping I can keep going as long as I can," Prestholdt said.
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