None expected (maybe only few) that this will work.
Press Release Source: Neurogen Corporation
Neurogen Reports Phase IIa Clinical Trial Results for Oral RA Drug
Tuesday June 15, 6:39 pm ET
BRANFORD, Conn., June 15 /PRNewswire-FirstCall/ -- Neurogen Corporation (Nasdaq: NRGN - News), a small molecule drug discovery and development company, today announced preliminary results from its Phase IIa clinical trial using NGD 2000-1, one of the first oral C5a antagonists to be tested in humans, for the treatment of rheumatoid arthritis (RA). This exploratory trial was designed to evaluate the potential benefit of blocking the C5a receptor in patients with mild to moderate RA. (see "Clinical Protocol" section below)
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In the study, NGD 2000-1 did not demonstrate an effect with respect to the trial's primary endpoint, change in C-reactive protein (CRP), a biomarker of disease activity derived from patient blood samples. Secondary clinical endpoints reflecting signs and symptoms of disease and which are components of the ACR composite index of disease severity were also examined in the trial. NGD 2000-1 demonstrated a statistically significant result (p=0.041) on a secondary responder analysis endpoint, Subject Global Assessment of Disease Activity, at a dose of 100 mg BID (twice daily). While other secondary endpoints were statistically non-significant, trends favoring NGD 2000-1 treatment groups were seen.
A post hoc analysis of the ACR 20 response derived from the primary and secondary endpoints revealed a statistically significant response (p=0.014) at the highest dose tested, 100 mg BID. While the calculation of an ACR response was not a pre-specified endpoint in the study, all components of the ACR index were included in the study as primary or secondary endpoints. A trend toward significance on the ACR 20 scale was observed at the 10 mg (p=0.093) and 60 mg (p=0.096) BID doses.
William H. Koster, PhD, President and CEO of Neurogen commented, "While data from the study are still coming in and will require further analysis, the preliminary data we have today indicates that we would need to develop NGD 2000-1 at dose levels that would not permit a sufficient therapeutic window. Given the previously reported inhibition of the CYP 3A4 enzyme, creating the potential for drug-drug interactions, and the dose levels we now expect to be required for efficacy, we currently believe it is unlikely that we will further develop NGD 2000-1 for the adult RA population.
Dr. Koster continued, "The ACR 20 results observed at the 100 mg BID dose, and activity trends seen within the trial, offer encouraging support for the potential benefit of blocking the C5a receptor. As we fully digest the results of this study over the coming months we plan to continue profiling other compounds from our C5a program with a greater potential therapeutic window -- having greater potency and reduced potential for reduced drug-drug interactions and side effects."
NGD 2000-1 Phase IIa Clinical Protocol
The safety, pharmacokinetics, and efficacy of NGD 2000-1 for the treatment of RA were assessed in a randomized, double-blind, placebo controlled study of patients with mild to moderate RA. The trial encompassed 49 patients in 8 clinical centers. Patients were dosed twice daily for 14 days with either placebo (n = 12), 10 mg (n = 12), 60 mg (n = 13), or 100 mg (n = 12) of NGD 2000-1. The treatment period was preceded by a two week screening period and followed by a two week post-treatment follow-up period. No concomitant disease modifying anti-rheumatic drugs (DMARDs) were permitted during the trial. Certain drugs which are metabolized by the liver enzyme CYP 3A4 were prohibited during the trial due to the inhibition of this enzyme by NGD 2000-1 identified during Phase I studies.
The primary endpoint for the trial measured movement of C-reactive protein (CRP), as a biomarker for disease activity derived from patient blood samples. Secondary endpoints included an assessment of disease signs and symptoms: number of swollen joints, number of painful joints, subject pain, subject global assessment of disease activity, physician global assessment of disease activity, and a health assessment questionnaire. |
