Vicore Pharma Holding AB (publ), has announced an updated interim analysis of its AIR phase 2a trial with C21 in idiopathic pulmonary fibrosis (IPF).
With 51 patients enrolled, the data demonstrates that C21 has the potential to transform the treatment of IPF and restore lung function. The disease is currently considered to be incurable and inevitably progressive.
Vicore said the data show C21 continues to be safe and well tolerated with no treatment-related serious adverse events, and that C21 continues to demonstrate long-term efficacy. At 36 weeks the average forced vital capacity (FVC) had increased to +350 mL over baseline, which is +530 mL over the expected trajectory of untreated patients.
Vicore plans to progress clinical development of C21 through initiation of a phase 2b trial (ANDAS) and will conclude recruitment to the AIR trial.
Toby Maher, Keck School of Medicine at University of Southern California, said: “The magnitude of FVC stabilization seen with C21 in the AIR trial is very different from what we normally see in clinical practice and certainly gives hope for patients. If data are replicated in the ANDAS trial, there will be a fundamental change in how IPF is treated with an opportunity to stop progression and restore lung function.”
The AIR trial, a multi-center, open label, single arm 24-week trial with a 12-week extension studying the safety and efficacy of the angiotensin II type 2 receptor agonist (ATRAG) C21 in patients with IPF, has now enrolled 51 patients. At the time of analysis, 27 patients had completed 24 weeks of treatment with an average increase in FVC of +50mL and a 3-visit average increase of +110 mL, and 19 patients had completed 36 weeks of treatment with an average increase in FVC of +350 mL and a 3-visit average increase of +220 mL.
Of the 19 patients that had completed 36 weeks of treatment, 17 presented an FVC value that was better than what would have been expected of an untreated population. The new dataset shows a stabilization of lung capacity already at week 6 and, in line with previous interim analysis, a subsequent increase of FVC from weeks 16 to 36. Now, with twice the number of patients versus the interim analysis announced in November 2022, the previously reported early stabilization followed by an increase in lung function is confirmed, suggesting that C21 has the potential to transform the treatment of IPF.
Carl-Johan Dalsgaard, CEO of the Swedish biotech company, said: “The long-term stabilization and increase in FVC is unique for patients treated with C21 and consistent with the mechanism of action of an ATRAG. Restoring alveolar integrity is key in treating IPF and that is what C21 is doing.”
C21 continued to be safe and well tolerated with no treatment-related serious adverse events; there was a low rate of disease progression or worsening of cough and no gastrointestinal tolerability issues. 94% and 96% of patients at week 12 and 24, respectively, showed a positive benefit/risk, according to a joint benefit/risk assessment by the patients and principal investigator.
Recruitment to the AIR trial will be concluded to fully focus on the next step of development, the phase 2b ANDAS trial.
Rohit Batta, CMO of Vicore said: “We are thrilled to see that the previously reported long-term stabilization and increase in FVC holds through with now double the number of patients in the AIR trial. These results are truly encouraging with regard to the future clinical development of C21 and our ambition to provide a treatment for IPF patients as soon as possible.”
Biomarkers further validate C21 results
The clinical findings with FVC have been confirmed with relevant biomarkers, increasing the confidence in C21. FVC correlated strongly with lung volume as measured in 3D reconstructions of CT scans, reinforcing the accuracy of the FVC measurements.
Patients with early IPF disease showed significantly less end-terminal fibrosis in the scans and a higher degree of FVC increase 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 biomarker TGFb1 was reduced from baseline by 57% at 24 weeks, suggesting a reduced fibrosis drive. TGFb1 is a key mediator of fibrosis and its reduction has consistently been seen in cell cultures, animal models as well as in slices of human IPF lung tissue exposed to C21.
Other companies working on IPF include Redx, a clinical-stage biotech company, which last year announced it is trialing RXC007. RXC007 is a rho associated coiled-coil containing protein kinase 2 (ROCK2) selective inhibitor as a potential treatment for IPF.