Basilea's FGFR inhibitor derazantinib has taken another important step in the right direction with the publication of positive topline results from the FIDES-01 study.
These results after 12 months confirm and complement the 6 month data previously reported in patients with advanced or inoperable bile duct (biliary) cancer (intrahepatic cholangiocarcinoma) who have been selected because they harbour an FGFR2 gene fusion (cohort 1 in FIDES-01). After treatment with derazantinib for 12 months, the overall response rate (ORR), which was the primary endpoint for the study, was 20.4% (21% previously), while the disease control rate (DCR) was 72.8% (83% previously). The median progression-free survival (PFS) in patients was 6.6 months. It is important to note that the data are not fully mature, with12 patients still ongoing, including 3 patients with a partial response. The safety profile of derazantinib continues to look manageable with hyperphosphataemia, weakness, and raised liver enzymes the main issues; derazantinib continues to harbour a low level of nail toxicities and retinopathy suggesting some differentiation in the increasingly competitive FGFR class.
We also await the data from cohort 2 in iCCA patients with FGFR2 gene mutations or amplification, however, we believe the result to have been de-risked following a previous positive post hoc analysis of a Phase 1/2 study in 44 patients with locally advanced, inoperable or metastatic iCCA. The DCR was 67% compared to 83% for gene fusions, and success here would be another important differentiating feature for derazantinib versus other FGFR inhibitors.
The FGFR class is becoming more competitive, with others ahead of derazantinib in the two lead indications of biliary cancer (iCCA) and urothelial cancer. However, the prospects for derazantinib are linked to its ability to boost the effectiveness of checkpoint inhibitors, such as Roche's Tecentriq, particularly in those indications where activity in monotherapy is lacking (e.g. urothelial cancer). There are several reasons to believe that the result should be supportive; this includes the observation that 25% of patients in the successful Balversa pivotal study in urothelial cancer had previously received checkpoint inhibitor therapy. We have previously suggested that much now depends on Basilea's ability to prove that the additional capability of derazantinib to inhibit the CSF-1/CSF1R pathway can augment the checkpoint inhibitor class. We believe that there are reasons to be encouraged given that the CSF1R inhibitor class has been validated with the approval of Turalio. Importantly, although this remains a novel class, the potential to combine with checkpoint inhibitor is ongoing with emerging data providing support and manageable toxicities. Adding coverage of another pathway could provide relief from tumour escape mechanisms and emerging resistance. We believe that the addition of an FGFR inhibitor like derazantinib can only be helpful in this regard. The data today are important confirming the activity of derazantinib in a patient population that we know are already tractable to this approach. With the intensifying competitive noise, we suspect it will be the interim result of FIDES-02 in 2021, evaluating the checkpoint inhibitor combination in urothelial cancer, which will drive appreciation of derazantinib's broader potential. Should these data prove positive, there will be greater expectations for the combination in the larger and more needy gastric cancer setting.
We have calculated a discounted cash flow fair value of CHF 120 for Basilea.
IMPORTANT:
Basilea Pharmaceutica is a client of Calvine Partners and as such, this publication is not independent and should be considered a marketing communication under FCA Rules. None of the information contained in this publication should be considered as any form of advice.