Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. IPF appears to be heterogeneous in pathobiology with ∼40% of IPF patients found to have elevated levels of circulating antibodies to the autoantigen type V collagen (col(V)).Following a targeted, precision medicine approach, we conducted a phase 1 study to test the safety and explore potential efficacy of IW001, a col(V) oral immunotherapeutic developed to treat antibody-positive IPF patients. We divided 30 antibody-positive IPF patients into three cohorts for daily dosing over a 24-week period.All patients completed treatment without serious adverse events, acute exacerbations or IPF-related hospitalisations. A decline in lung function occurred in the lowest-dose cohort that was comparable to that reported in placebo arms of published IPF trials. In contrast, the highest-dose cohort showed a trend toward stabilisation of forced vital capacity and matrix metalloproteinase 7, and a reduction in binding of C1q to anti-col(V) antibodies.IW001 may modulate the immune response to col(V) and may represent a new therapeutic for col(V)-reactive IPF patients. @ERSpublications IW001 is safe, and improves biomarkers and lung function in IPF patients with type V collagen antibodies http://ow.ly/LirbO

Where do we go from here? Clinical drug development in idiopathic pulmonary fibrosis

“…Indeed, it was the mechanistic marker anti-collagen V antibody-bound C1q that showed the most consistent results. Although not statistically significant, C1q binding appeared to be reduced by oral immunotherapy in a dose-dependent manner, and 24-week change in C1q binding appeared correlated with 24-week change in FVC [4].…”

“…All of these areas represent potential upstream targets for novel therapeutics. WILKES et al [4] demonstrate that clinical research using cohorts of carefully phenotyped patients with accompanying biological samples can identify a plausible target, in this case autoimmunity against collagen V, with a potential therapeutic intervention. We need more of these types of programmes that use clinical and biological data from patients with IPF to identify potential aetiological pathways and test compounds that may modify them.…”

“…WILKES et al [4] use a precision medicine approach to identify a sizable subgroup of IPF patients with elevated autoantibody levels to collagen V and hypothesise that therapy directed at modulating the immune response to collagen V will preferentially benefit these patients. Importantly, this early stage study provides no proof of this hypothesis, and there is a danger of false dichotomisation in precision medicine that deserves careful consideration.…”

“…WILKES et al [4] incorporate molecular biomarkers into their study, including matrix metalloproteinase 7, serum albumin, and anti-collagen V antibody-bound C1q, a mechanistic biomarker. The more effective oral immunotherapy with type V collagen is in reducing anti-collagen V antibody activity, the less C1q should be bound by anti-collagen V antibodies in the serum.…”

“…The innovative study by WILKES et al [4], published in this issue of the European Respiratory Journal, describing the phase 1 results of oral immunotherapy with type V collagen in patients with IPF illustrates one such approach. This study is worth careful consideration, both for the novelty of its potential therapy and for the approach it takes to three core study design issues.…”