Basilea's FGFR inhibitor derazantinib finds itself in an intensely competitive field. However, clinical studies are ongoing to position derazantinib optimally versus its peers erdafitinib, pemigatinib and infigratinib.
We sense concerns that derazantinib, as a fast follower, would struggle to gain market share against incumbent therapies unless it offers an added benefit. Different FGFR inhibitors have subtly different kinase inhibition profiles, which should lead to varying degrees of differentiation. The safety profile is important in this regard, and derazantinib fares well with reduced retinal side effects, stomatitis, hand foot syndrome and nail toxicity compared to its peers.
Bile duct cancer has served as an important proof of concept indication for the class generally, with derazantinib’s activity at first glance perhaps deemed less potent than others. From an efficacy perspective, it is challenging to make comparisons without the benefit of direct head-to-head studies. However, comparisons will inevitably be made on published data and in this regard, we concede that on measures such as ORR and DCR, other FGFR inhibitors perhaps look more impressive. Still, from our perspective, it is important to note that on the more patient-relevant PFS endpoint, derazantinib looks highly competitive. Data reported at ESMO from a more mature dataset suggests a median PFS of 8 months in FGFR2 gene fusion iCCA patients. In the modest bile duct cancer indication, it is also important to remember that derazantinib's potential differentiation has been re-enforced with encouraging data in those patients with gene mutations and amplifications (as well as fusions).
Ultimately, the success of derazantinib will be dependent on its ability to compete in the more significant bladder cancer and gastric cancer indications, with studies ongoing (FIDES-02 and FIDES-03). For us, it is the potential activity also against CSF1R, promising to boost the activity of the checkpoint inhibitors (CKIs), which offers a key differentiator for derazantinib. While bladder cancer may be more competitive, in gastric cancer the opportunity for derazantinib is still wide open. More recently, Basilea has sought to further capitalise on derazantinib’s better tolerability profile with a dose intensification strategy. Data on the combination with CKI atezolizumab start later this year (FGFRi refractory patients), with the results of the dose intensification in urothelial cancer in 2022. Positive data here should lead to a much greater appreciation of derazantinib in a highly competitive drug class.
We have calculated a discounted cash flow fair value of CHF120 for Basilea.
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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.