Infergen

Clinical Pharmacology

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Clinical Pharmacology

Infergen

Sustained response rates by ALT normalization and HCV RNA reductions to below detectable limits are included in Table 1. Among the Infergen treatment groups in this study, the 9 mcg dosage arm demonstrated a similar efficacy profile when compared to the IFN alfa-2b dosage arm. The 3 mcg Infergen dosage arm had lesser efficacy; 3% of patients receiving 3 mcg Infergen had sustained reductions in their ALT concentrations to within the normal range and 3% had sustained reductions in HCV RNA to below detectable limits.

Table 1. Rates (95% CI^a) of ALT Normalization and HCV RNA Reductions to Below Detectable Limits in Previously Untreated Patients
	End of 24-week Treatment		End of Observation (Sustained Response Rate)
	Infergen 9 mcg n=232	IFN alfa-2b 3 MIU^b n=240	Infergen 9 mcg n=232	IFN †?-2b 3 MIU^b n=240
Normalized ALT	39% (33%, 46%)	35% (29%, 41%)	17% (12%, 22%)	17% (13%, 22%)
HCV RNA Negative	33% (27%, 39%)	25% (19%, 31%)	9% (6%, 14%)	8% (5%, 13%)
^a CI = Confidence Interval. ^b 3 MIU IFN α-2b is equivalent to approximately 15 mcg IFN α-2b.

In this study, liver biopsies were taken at baseline and at the end of post-treatment observation. Similar improvement in liver histology, assessed by HAI score,⁵ was observed in the 9 mcg Infergen (68%), 3 mcg Infergen (63%), and IFN alfa-2b (65%) dosage arms.

Subsequent Treatment

Subsequent treatment with 15 mcg of INFERGEN for 24 and 48 weeks was evaluated in an open-label clinical trial in 208 patients who had failed initial therapy for 24 weeks with either 9 mcg INFERGEN or 3 mIU (approximately 15 mcg) IFN (alpha)-2b.⁷ Of these patients, 133/208 had failed to normalize ALT during the initial treatment period. Seventy-five of 208 achieved normal ALT during initial treatment, but experienced relapse (return of abnormal ALT) during posttreatment observation. Patients were assessed for normalization of ALT (ALT response rate) and HCV RNA reduction to less than 100 copies/mL (HCV response rate) at the end of 24 weeks of observation following discontinuation of therapy. Sustained response rates measured by ALT normalization and HCV RNA reductions to below detectable limits for patients who received subsequent treatment with 15 mcg of INFERGEN are included in Table 2.

Patients who received 48 weeks of interferon therapy were more likely to experience a sustained response than were those who received 24 weeks of therapy. Similarly, patients who normalized their serum ALT but subsequently relapsed following initial therapy were more likely to experience a sustained response than those who were refractory to initial therapy.

**Table 2. Sustained Response Rates (95% CI) of ALT Normalization and HCV RNA Reductions to Below Detectable** **Limits After Subsequent Treatment ^b with 15 mcg INFERGEN**
	All Patients		Prior Nonresponders		Prior Relapsers
	24 Weeks n = 107	48 Weeks n = 101	24 Weeks n = 74	48 Weeks n = 59	24 Weeks n = 33	48 Weeks n = 42
End of Observation Normalized ALT	13%	19%	7%	7%	27%	36%
End of Observation Normalized ALT	(7.3%, 21.0%)	(11.7%, 27.8%)	(2.2%, 15.1%)	(1.9%, 16.5%)	(13.3%, 45.5%)	(21.6%, 52.0%)
End of Observation HCV RNA Negative	9%	22% ^a	4%	12%	21%	36%
End of Observation HCV RNA Negative	(4.6%, 16.7%)	(13.4%, 30.0%)	(0.9%, 11.5%)	(4.9%, 22.9%)	(9.0%, 38.9%)	(21.6%, 52.0%)
^a P value = 0.01.
^b Subsequent treatment data are presented for patients initially treated with 9 mcg INFERGEN or 3 MIU IFN (alpha)-2b in the initial treatment study; patients initially treated with 3 mcg INFERGEN were excluded from this analysis.