CRx-170

A combination of the known analgesic activity of tricyclic antidepressants and anti-inflammatory activity of glucocorticoid steroids for the treatment of chronic pain.

• Description: Novel selective cytokine modulator combining nortriptyline, an antidepressant, and a low dose of the steroid prednisolone.
• Data: Analgesic activity in preclinical pain models. Validation of biologic activity in a proof-of-concept asthma study.
• Formulation: Developing a once-daily capsule for nighttime administration.
• Commercial Opportunity: Convert existing tricyclic antidepressant use for chronic lower back pain and capture market share from alternate classes across all chronic pain syndromes.

Chronic lower back pain afflicts 11.7 million patients in the U.S.

Status: Currently on hold with no further development investment.

Clinical Results:

Asthma

We investigated a version of CRx-170 with the steroid budesonide in a phase 2a clinical trial in the United Kingdom in 17 asthma patients (Full News Release).

CRx-170 provided benefit on important clinical measures such as FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity) and PEF (peak expiratory flow) and demonstrated activity on immuno-modulatory markers.

• As measured by FEV1, the standard clinical measure of breathing capacity in asthma and chronic obstructive pulmonary disease (COPD), the CRx-170 combination containing budesonide, after one week of treatment, demonstrated a statistically significant 6% (p=0.045) mean percentage improvement (increase) in FEV1. Neither of the CRx-170 components alone, low-dose nortriptyline as a single agent nor low-dose budesonide as a single agent, showed significant improvement in FEV1.
• CRx-170 did not show a modulation of the inflammatory marker, CD163, the primary endpoint, although nortriptyline clearly did decrease CD163 on its own.
• CRx-170 was generally well tolerated, and there were no serious adverse events reported. The most common adverse events related to CRx-170 that occurred with a frequency of greater than 5% were dry mouth, drowsiness, constipation and headache, known effects of nortriptyline.