Welcome to your weekly digest of approaching regulatory and clinical readouts. Before the end of the year Allergan should release data in atopic dermatitis with its newly acquired topical treatment VTP-38543. Following Allergan’s buyout of Vitae Pharma last month, the results will go some way to determining whether this was good value for money.
Arqule meanwhile could be due for a big jump in valuation should the phase III Metiv-HCC trial of tivantinib in liver cancer return positive data. This is the only project in the Massachusetts group’s pipeline with any significant forecasts, so it needs good news to gain investor interest
In September Allergan bought Vitae for $639m, a 159% premium, latching onto the company’s dermatology products VTP-43742 and VTP-38543. Phase IIa data on the latter in atopic dermatitis are expected before the end of the year (Vitae buyout marks another comedown for exuberant biotech bulls, September 14, 2016).
VTP-38543 is a liver X-receptor beta agonist. The trial recruited 104 adults with mild-to-moderate atopic dermatitis, where VTP-38543 is applied topically twice daily for 28 days versus a placebo comparator. Three doses are being tested: 0.05, 0.15 and 1.0%.
The primary endpoints are associated with safety and include an analysis of treatment-related adverse events. Secondary measures cover maximum plasma concentration, half-life and severity scoring including investigator’s global assessment or IGA, which is important for a US filing.
There are no prior clinical data for this product in this indication so it is difficult to determine how it might perform. However, the company’s August corporate presentation provided some hints and the focus on ‘totality of data’ might suggest that not all of the efficacy endpoints have shown activity.
The presentation goes on to note that a high vehicle response rate is typical in atopic dermatitis trials. As the placebo comparator is cream-based it is likely to have a moisturising effect on dry skin as was also evident for Pfizer/Anacor’s topical treatment crisaborole, which is ahead of Vitae’s with a date with the US regulators in January.
The dermatitis space is a swiftly changing market in which Sanofi/Regeneron’s injectable dupilumab is looming large with a PDUFA date set for March next year. However, topical creams could be favoured by the payers.
Liver on a prayer
Arqule has forecast readout of Metiv-HCC at the end of 2016 or the start of 2017. This trial is in second-line hepatocellular cancer (HCC) in patients whose tumours have high expression of C-Met protein, which correlates with shorter survival.
Tivantinib binds to the Met receptor and aims to block cell growth triggered by hepatocyte growth factor. In non-small cell lung cancer, the drug failed to show efficacy, an event that crashed Arqule shares back in 2012. The group soldiered on in HCC, looking to confirm the findings of a phase II trial that extended the time to progression when compared with placebo.
Metiv-HCC, primarily sponsored by US and European licensee Daiichi Sankyo, has enrolled 368 patients whose HCC has progressed following treatment with Nexavar. The primary endpoint is overall survival as measured against a placebo control arm.
Earlier this year, the Metiv-HCC data monitoring committee authorised continued dosing with tivantinib following an interim analysis, which means there was not enough evidence to either stop the trial because of efficacy or because tivantinib does not work.
A second phase III trial in Japan, Jet-HCC, sponsored by Asian licensee Kyowa Hakko Kirin, is underway and could read out on a similar timeline to Metiv-HCC.
Should tivantinib succeed in the clinic and receive regulatory approval, it will have an additional challenge in the market. Since the HCC phase III began in 2012, Bayer has seen success in second-line treatment with Stivarga, which was tested in all comers rather than a biomarker defined population as tivantinib has been. Tivantinib will need to outperform Stivarga’s 2.8-month advantage in overall survival in the c-Met expressing population order to gain commercial traction.