A week after its immuno-inflammatory disease drug fell short in a Phase II study, CombinatoRx Inc. reported some better news with its asthma candidate, CRx-170.
Although CRx-170 did not indicate a change in inflammatory marker CD163, which had been the primary endpoint of the 17-patient Phase II proof-of-concept study, results did show that patients receiving CRx-170, a combination candidate containing low doses of the drugs budesonide and nortriptyline, demonstrated a statistically significant improvement in lung function.
Following one week of dosing, patients receiving the combination drug demonstrated a mean percentage improvement in FEV1 (Forced Expiratory Volume over one second) pulmonary function test of about 6 percent, whereas neither low doses of nortriptyline or budesonide as single agents showed significant improvement.
In the late allergen response skin test, the administration of CRx-170 reduced the LAR area by more than 50 percent.
The most common adverse events were dry mouth, drowsiness, constipation and headache, all of which are known side effects of nortriptyline.
CombinatoRx did not return calls seeking comment, but the company said in its press release that the Phase II data support further clinical development of CRx-170 in asthma and chronic obstructive pulmonary disease.
The trial enrolled patients with mild allergic asthma, and each received decreasing oral doses of nortriptyline and budesonide as single agents, followed by washout periods and then a one-week treatment of nortriptyline and one-week treatment with CRx-170.
CombinatoRx's goal is to create syncretic therapies by combining a pair of existing drugs to effectively attack immuno-inflammatory diseases and cancer along multiple cellular pathways. Drug candidates are discovered using the company's combination high-throughput screening technology.
So far, clinical results from the combination products have been mixed. In February, the company abandoned work on CRx-140, comprising low doses of cyclosporine and loratadine, following a Phase II miss in psoriasis. But it reported positive Phase II data in January with CRx-102, a combination of prednisolone and dipyridamole, in patients with osteoarthritis of the hand. (See BioWorld Today, Jan. 31, 2006, and Feb. 23, 2006.)
Earlier this month, the company's CRx-119, a combination of low doses of the steroid prednisolone plus amoxapine, missed its primary endpoint, as well as a secondary endpoint, in a Phase II study in patients with chronic adult periodontitis. In that case, CombinatoRx said it plans to conduct further analysis and await results of a second Phase II trial of CRx-119 - that one in rheumatoid arthritis - before attempting to draw conclusions about the drug's efficacy in immuno-inflammatory diseases. (See BioWorld Today, April 11, 2006.)
The company's pipeline also includes CRx-139 (prednisolone plus a selective serotonin reuptake inhibitor) and CRx-150 (an antidepressant plus a cardiovascular drug) in immuno-inflammatory diseases, and CRx-026 (chlorpromazine plus pentamidine) in development against multiple tumor types.
In the fall, the firm went public through a $42 million initial offering, selling 6 million shares at $7 apiece, followed up by a $48 million private placement last month.
Shares of CombinatoRx (NASDAQ:CRXX) closed at $10.35 Tuesday, down 3 cents.