Vicore Pharma Holding AB (publ), has announced a recent interim analysis of a phase 2a trial of AIR with C21 in idiopathic pulmonary fibrosis (IPF).
With 51 patients enrolled, the data suggest that C21 has the potential to transform IPF treatment and restore lung function. This disease is currently considered incurable and definitely progressive.
Vicore says data shows C21 continues to be safe and well tolerated without serious treatment-related side effects, and that C21 continues to demonstrate long-term efficacy. At 36 weeks the mean forced vital capacity (FVC) had increased to +350 mL from baseline, which was +530 mL over the trajectory expected in untreated patients.
Vicore plans to advance C21 clinical development through the initiation of a phase 2b trial (ANDAS) and will conclude recruiting for the AIR trial.
Toby Maher, Keck School of Medicine at the University of Southern California, said: “The magnitude of FVC stabilization seen with C21 in the AIR trial is very different from what we usually see in clinical practice and is certainly encouraging for patients. If the data is replicated in the ANDAS trial, there will be a fundamental change in the way IPF is treated with the opportunity to arrest progression and restore lung function.”
The AIR trial, a 24-week multi-center, open-label, single-arm trial with a 12-week extension studying the safety and efficacy of C21 angiotensin II type 2 receptor (ATRAG) agonists in patients with IPF, has now enrolled 51 patients. At the time of analysis, 27 patients completed 24 weeks of treatment with an average increase in FVC +50 mL and a mean increase of 3 visits +110 mL, and 19 patients completed 36 weeks of treatment with an increase in average FVC. +350 mL and an average increase of 3 visits of +220 mL.
Of the 19 patients who had completed 36 weeks of treatment, 17 displayed FVC values that were better than would be expected from the untreated population. The new data set shows stabilization of lung capacity at week 6 and, in line with the previous interim analysis, a subsequent increase in FVC from week 16 to 36. Now, with double the number of patients compared to the provisional analysis announced in November 2022, The previously reported initial stabilization followed by improvement in lung function was confirmed, indicating that C21 has the potential to transform IPF treatment.
Carl-Johan Dalsgaard, CEO of the Swedish biotechnology company, said: “The long-term stabilization and improvement of FVC is unique to patients treated with C21 and is consistent with the mechanism of action of ATRAG. Restoring alveolar integrity is key in treating IPF and that is exactly what C21 does.”
C21 continues to be safe and well tolerated without serious treatment-related side effects; there is a low rate of disease progression or worsening cough and no gastrointestinal tolerance problems. 94% and 96% of patients at weeks 12 and 24, respectively, demonstrated a positive benefit/risk, according to a joint benefit/risk assessment by the patient and the primary investigator.
Recruitment for the AIR pilot will be closed to fully focus on the next development step, the ANDAS phase 2b pilot.
Rohit Batta, CMO of Vicore said: “We are pleased to see that the previously reported long-term stabilization and improvement in FVC holds by now doubling the number of patients in the AIR trial. These results are really encouraging with respect to the future clinical development of C21 and our ambition to make treatment available to IPF patients as soon as possible.”
The biomarker further validated the C21 results
Clinical findings with FVC have been confirmed with relevant biomarkers, increasing confidence in C21. FVC correlates strongly with lung volumes measured in 3D CT scan reconstructions, strengthening the accuracy of FVC measurements.
Patients with early IPF disease showed significantly less late terminal fibrosis on scans and a higher rate of FVC elevation after 36 weeks of treatment compared to patients with established IPF. This is in line with the C21 mechanism of action, promoting alveolar repair.
The TGFb1 biomarker was reduced from baseline by 57% at 24 weeks, indicating decreased fibrosis drive. TGFb1 is a major mediator of fibrosis and its reduction has been consistently seen in cell cultures, animal models, and human IPF lung tissue slices exposed to C21.
Other companies working on IPF include Redx, a clinical-stage biotech company, which announced last year it was trialling RXC007. RXC007 is a related coiled-coil containing selective protein kinase 2 (ROCK2) inhibitor as a potential treatment for IPF.