Washington Editor

Allos Therapeutics Inc.'s stock soared 61.5 percent Thursday after the company said it would file a new drug application for a synthetic small molecule shown to double median survival time in breast cancer patients.

Allos, of Westminster, Colo., intends to begin filing a rolling new drug application for the candidate, currently referred to as RSR13 (efaproxiral), in the third quarter, with an expected completion by the end of the year.

To be sure it has adequate resources to carry it through the regulatory process, Allos plans to cut its staff by 30 percent, temporarily suspend development of BGP-15 as a chemoprotectant and stop screening patients in the Phase III trial of RSR13 in primary non-small-cell lung cancer in the U.S. The company hopes to sign a partner to assume responsibilities for RSR13 in NSCLC.

Allos' stock (NASDAQ:ALTH) closed Thursday at $3.73, up $1.42.

Allos had $53 million in cash at the end of the first quarter. As a result of the revised operating plan, the company believes it will reduce its cash burn to $6 million to $7 million per quarter and expects its loss from operations for 2003 to be in the low $30 million range, including current-year restructuring charges and noncash compensation.

Under the best of circumstances, RSR13, a fast-track candidate, could make it to market next summer for patients with metastatic breast cancer who have developed metastases to the brain.

It was in the breast cancer subset of 538 brain metastases patients that the company noted a statistically significant improvement in median survival in the pivotal Phase III trial. The randomized, open-label study was designed to compare the safety and efficacy of whole-brain radiation therapy (WBRT) combined with RSR13 to WBRT alone in patients with brain metastases. Of the total population, 56 percent had NSCLC, 21 percent (or 115 patients) had breast cancer and 23 percent had other cancers. The primary endpoint was overall survival. (See BioWorld Today, April 24, 2003.)

In April, Allos' stock took a hit, falling 44.1 percent, or $1.50, to close at $1.90 when it said preliminary analysis of the Phase III trial showed it failed to meet a statistical endpoint in patients with brain metastases. Nevertheless, the company saw activity in the breast cancer patients.

Median breast cancer survival rates had increased from about 4.57 months to 8.67 months due to RSR13 (p=0.006).

When asked to describe the significance, Michael Hart, company president and CEO, told BioWorld Today, "There's never been a radiation sensitizer that has shown a survival benefit like RSR13 in a randomized Phase III trial."

Meanwhile, David Bouchey, vice president of health care equity research at CE Unterberg, Towbin in Denver, told BioWorld Today, "Survival rates in this group of patients haven't been improved in decades. Here you can double it. It may be three or four months, it may be one more Christmas or one more wedding anniversary or one more grandson's birthday, whatever it is to the individual patient, it means a lot to the oncology community."

While all that may be true, brain metastases from breast cancer were not a prespecified subset, and generally the FDA takes a dim view on that type of filing, Bouchey said. "On the other hand, you've got 115 patients in a randomized, controlled setting where you've doubled or nearly doubled survival in one of the worst cancers."

The FDA frowns upon companies filing for approval using unspecified analysis because "it is possible to pull together data and present it in such a way that it really doesn't give you a realistic picture of what the drug's benefit and safety profile is. But that's not what's happening here - this drug came close to reaching an endpoint on a Phase III, it has benefit in some cancer patients and it has no side effects," Bouchey said.

Hart said he's aware that, historically, the FDA hasn't looked fondly on this type of filing, "but at the same time, I think if the data is compelling enough and stands up to their scrutiny, then they can decide as an agency whether or not they want to file it and put it before ODAC [Oncologic Drugs Advisory Committee]."

In a conference call with analysts late Thursday afternoon, several listeners questioned Hart about the merits of an application with only 115 patients.

But Hart stood his ground, saying the Phase III was randomized, controlled and "it took 29 months to enroll 115 breast cancer patients and that is no small feat."

Bouchey estimates the U.S. patient population in the breast cancer indication at 40,000 to 60,000 annually. He wouldn't estimate future sales of RSR13, saying the company has not discussed pricing

RSR13 increases the release of oxygen from hemoglobin, which is important in treating hypoxia in connection with radiation treatments for cancerous tumors. RSR13 is designed to enhance radiation therapy by making it more effective.

In the Phase III trial, patients receiving RSR13 plus WBRT experienced a 17.6 percent improvement in median survival compared with patients receiving WBRT alone (5.26 months vs. 4.47 months; p=0.17; n=538). In the prospectively defined intent-to-treat group of patients with brain metastases from only breast cancer and NSCLC, patients receiving RSR13 had a 32.4 percent increase in median survival vs. control (5.91 vs. 4.47 months; p=0.12; n=414).

Also, the company said there was a 48 percent increase in median survival among patients in the breast and NSCLC intent-to-treat subgroup who were diagnosed with their original cancer before they were diagnosed with brain metastases and were treated with RSR13 plus WBRT (6.60 months vs. 4.47 months; p=0.003; n=273).

Allos intends to continue its Phase I/II trials of RSR13 in cervical cancer and recurrent glioblastoma. Also, Hart said the company will continue the PDX development program for NSCLC, mesothelioma and non-Hodgkin's lymphoma. PDX is a novel small-molecule, cytotoxic, injectable antifolate (DHFR inhibitor).