By Kim Coghill
A delayed side effect in cancer patients participating in clinical trials of Skeletal Targeted Radiotherapy prompted NeoRx Corp. to suspend its Phase III studies.
Seattle-based NeoRx, makers of Skeletal Targeted Radiotherapy (STR) for the treatment of multiple myeloma, stopped its Phase III clinical trials when four patients treated at one of the major Phase I/II study sites developed delayed toxicity referred to as TTP/HUS, or thrombotic thrombocytopenic purpura/hemolytic uremic syndrome.
"We have suspended patient accrual and treatment on all STR studies until we resolve these matters with the FDA," said Paul Abrams, NeoRx's CEO.
NeoRx received a letter Monday from the FDA suspending the STR trials until further information is supplied and evaluated by the FDA.
NeoRx's stock (NASDAQ:NERX) closed Wednesday at $9.375, down $8.062, or 46 percent.
STR delivers high-dose radiation directly to the tumor and bone with minimal exposure to other drugs.
An independent Data Safety Monitoring Board (DSMB) investigated the side effect and unanimously recommended that the Phase III study proceed, but with additional monitoring and standardization of study methods.
"The next step is to respond to the questions and requests that the FDA stated in their letter to us. We are collecting data and we believe we can respond to the FDA next week," Abrams said. "We believe that we can conduct the trial in such a way that it will be safe for the patients. But until we get permission to do so, we obviously are not going forward."
The Phase I/II trials were conducted at three sites, with two sites entering an overwhelming majority of patients, Abrams said. About 80 patients participated and the four affected were treated at the same site, leading investigators to believe that differences in procedure may have been a contributing factor.
According to a statement released by NeoRx, the method of STR administration at the only site reporting the syndrome differs from that used at the other major Phase I/II site and from the current Phase III protocol in several ways: the drug was infused more rapidly, the calculated dose to be received by the patients was somewhat higher, and the patients did not receive bladder irrigation during the procedure.
The company said that lack of bladder irrigation can result in a dose of radiation to the bladder wall that is threefold higher than in the irrigated patients. A large fraction of the patients who did not receive bladder irrigation developed blood in the urine, whereas to date, no patients who have had bladder irrigation had blood in the urine attributable to STR, according to a statement released by the company.
Bladder irrigation is required by the current Phase III protocol.
"Without knowing that a problem existed, we wrote the Phase III protocol in the way that the protocol [for Phase I/II] was written at a site that didn't have this problem," Abrams said. "But we can't tell what the impact will be on the Phase III protocol until we resolve all the issues that we need to resolve with the FDA and agree on how we will go forward."
Abrams said each of the four affected patients had at least two known potential triggers of TTP/HUS. Some triggers can include food contamination, toxic shock syndrome, post-viral infection, bone marrow transplantation and drug effects. TTP/HUS involves a combination of symptoms, including abnormal clotting of blood in small blood vessels. This can lead to anemia, a low platelet count that can result in bleeding, and potential damage to organs.
"We can't be certain that there's a relationship between our drug and this problem," Abrams said. "But when you are studying a new drug, you have to take the conservative view and raise the question about whether a problem may be due to your agent."
Abrams said TTP/HUS is a serious adverse event and "it needs to be regarded as life threatening."
About 10 to 15 years ago the treatments for TTP/HUS were ineffective, he said. "Today the treatments are much more effective and our patients to date have been improving and that's good news. The only patient who hasn't been improving is a patient who has progressive cancer, and that's a different issue."
The Phase III trials began in early October and approximately 20 cancer centers in the U.S. were expected to participate. The study was expected to enroll between 250 and 300 patients.