Following up on the spring news that the FDA had lifted its clinical hold on the company's Skeletal Targeted Radiotherapy program - news that sent NeoRx Corp.'s stock skyrocketing - the firm said it has reached an agreement with the agency for a Phase III trial protocol.
Jack Bowman, chairman and CEO of Seattle-based NeoRx, said in a conference call that getting STR to market is the company's "No. 1 priority," and a partner is being sought to help pay for the Phase III trials and assist in marketing. Enrollment in the trial testing STR against multiple myeloma is expected to begin in next year's first quarter.
Development is forging ahead with or without a partner, Bowman told BioWorld Today.
"We're not slowing down at all," he said.
Karen Auditore-Hargreaves, chief operating officer, said the company had $18.6 million at the end of the second quarter, with a burn rate "quite low" for 2003, between $3 million and $4 million per quarter.
"We know we need to raise money," she said, and the company is exploring several options for doing so.
NeoRx's shares (NASDAQ:NERX) fell 80 cents Wednesday, or 12.9 percent, to close at $5.39, still a major improvement over the $3.10 price after April's news that the FDA - which delayed the drug because of side effects in some patients - had lifted the hold. (See BioWorld Today, April 25, 2003.)
NeoRx had submitted results from a dosimetry study to the FDA in February, met with the agency in March and had been waiting.
STR delivers high doses of radiation to tumor sites in the skeleton with minimal damage to organs outside the bone, targeting bone and adjacent marrow with a small-molecule agent, known as DOTMP, combined with the radionuclide holmium-166.
Now, having gone through the agency's special protocol assessment procedure, NeoRx has reached a binding written agreement with the FDA under which, if the guidelines for trial design are followed and the results sought are gained, the company can claim approval-worthy efficacy in its new drug application.
NeoRx is aiming to conduct a randomized, controlled study of STR in patients with the primary, refractory form of bone-marrow cancer, enrolling about 240 evaluable subjects, half in the experimental arm and half as controls.
Auditore-Hargreaves said about one-third of patients with multiple myeloma have the primary, refractory form of the disease, with about 5,000 diagnosed each year in the U.S.
Patients in the experimental arm will get STR plus the chemotherapy drug melphalan, followed by autologous stem cell transplantation, and the control patients will get melphalan only, followed by transplantation.
The trial will be conducted at about 40 sites, Auditore-Hargreaves said.
As a surrogate endpoint, the FDA accepted complete response at six months, thus placing STR on the path to accelerated approval, although fast-track status and priority review are yet to be discussed.
The alternative to that endpoint is survival, "the gold standard for assessing drug efficacy," Auditore-Hargreaves said. "Obviously, the better your drug is, the longer your patients will live, and hence, ironically, the longer the period of follow-up before you can submit your NDA."
Fewer than 5 percent of multiple myeloma patients survive more than 10 years after diagnosis. Primary, refractory patients die in less than a year, she said.
Using the six-month, complete-response surrogate endpoint "potentially saves you several years in follow-up time," she said, adding the company "will, of course, follow all the patients in the trial for progression-free survival and overall survival," which the FDA has agreed is adequate to satisfy the Phase IV follow-up and gain full approval for STR in the sought indication.
Multiple myeloma has been much in the news with approval won in May for the proteasome inhibitor Velcade by Millennium Pharmaceuticals Inc., of Cambridge, Mass., which entered a $500 million deal for the product in July with Ortho Biotech Products LP, of Raritan, N.J., a unit of Johnson & Johnson. (See BioWorld Today, July 2, 2003.)
"We see Velcade and STR as being complementary," Auditore-Hargreaves told BioWorld Today, noting that Velcade "does not produce many complete responses - certainly in the single-digit range," whereas STR has been shown to yield a 25 percent to 40 percent complete response "depending on how you slice and dice the data."
Also, Velcade is indicated for end-stage patients with no other options, including stem cell transplant.
"Those aren't the patients we'd expect to get in any case," Auditore-Hargreaves said. Velcade might be used for earlier disease, she said, but "it's a stem cell-sparing agent. You can treat patients with a couple of courses and still be able to harvest their stem cells for transplants. They will eventually relapse and we'll get them at that point."