By Frances Bishopp
Neurobiological Technologies Inc. will not push Corticotropin-Releasing Factor (CRF) as a high priority for development as a treatment for rheumatoid arthritis, after the primary endpoint of a Phase II clinical trial did not show statistically significant activity.
Neurobiological stock (NASDAQ:NTII) closed down $1.25 Friday to $2.375.
Jeffrey Price, president and CEO of Neurobiological, told BioWorld Today, "We decided without the collaboration of a major corporate partner, we would not go forward and develop the drug on our own. We will be analyzing all the different parts of the trial, which will take us several weeks. What we have reported on is the primary endpoint of the trial which is an American College of Rheumatology [ACR] definition of an improvement for rheumatoid arthritis," Price said, "but there are a lot of things we are measuring in the trial and we will look at this data in great detail and we will present this final data to potential corporate partners to see if there is interest in pursuing CRF."
Neurobiological, of Richmond, Calif., has no partnering arrangements for any indications for CRF, a natural neuroendocrine peptide hormone, which, the company believes to have broad, anti-inflammatory activity, based on pharmacologic studies in animals. Due to its mechanism of inhibiting leakage from small blood vessels and capillaries, the company believes it has the potential to be applicable in a variety of serious conditions.
Neurobiological's stock fell $1.25 Friday on the news of the Phase II results for CRF. "They swung for the fence and struck out on this one," John Wong, an analyst with Van Kasper & Co., in Los Angeles, said. "But rheumatoid arthritis is a chronic disease and a lot of companies have failed in this area."
The trial probably should have been longer, Wong said, to see some real results.
Wong downgraded the stock from a buy to a long-term buy because "of other Neurobiological products that do extremely well in the clinic."
Patients enrolled in the study self-administered CRF or placebo by subcutaneous injection once a day for 14 days and were evaluated for an additional six weeks on the basis of improvements in tender joint counts, swollen joint counts and several other criteria defined by the ACR.
In the primary trial endpoint, 20 percent of patients receiving CRF experienced ACR-defined improvement in RA vs. 15 percent of patients receiving placebo.
The study enrolled 113 patients, including both patients who were receiving concomitant steroidal therapy and those who were not.
For most efficacy parameters, both CRF and placebo treatments resulted in statistically significant improvements from baseline. However, major differences between placebo and CRF treatments were generally not observed.
Based upon the Modified Health Assessment Questionnaire results, CRF-treated patients had statistically significant improvement in activities of daily living, whereas placebo patients did not.
In patients not on steroids, there was a trend toward greater ACR-defined improvement in RA in the CRF group compared to placebo.
"CRF does have a high anti-edema activity," Price said. In June 1996, Neurobiological reported positive results from Phase I/II trials in patients with brain edema associated with brain tumors.
"We are moving very aggressively to pursue this indication with the start of a significant Phase II trial later this quarter or the first half of the year," Price said.
On Dec. 18, 1996, Neurobiological reported that the Adult AIDS Clinical Trials Group initiated a Phase II clinical trial of the company's neuroprotectant Memantine, an orally administered NMDA receptor antagonist. The basic function of the NMDA receptor is essential for movement, sensation, memory and cognition.
The trial will evaluate Memantine's ability to reduce symptoms of demential and neuropathic pain in patients with AIDS.
Memantine is the first NMDA receptor antagonist to enter clinical trials from the company's neuroprotection program and this event was hailed as "a major milestone" by Price, who said additional Phase II trials of Memantine in other chronic indications would begin during 1997.
Wong said he believes Memantine will be the high profile drug for the company and is where investors should be focused. "Memantine will bring the stock and the company forward," Wong said. *