Preliminary data from a phase IIb trial of Allos Therapeutics’ Folotyn in non-small-cell lung cancer (NSCLC) have seemingly prompted more questions than answers.
Encouraging survival trends were reported. However, the lack of detail announced so far has allowed few firm conclusions to be drawn, although admittedly the trial was probably not powered enough to give a conclusive read out. The company is holding back full data for a medical conference. With disappointing third quarter sales of the drug in peripheral T-cell lymphoma (PTCL), also announced yesterday, it is probably not surprising that shares in the company fell, slumping 15% to $4.83, a 21-month low. A double whammy of some exemplary NSCLC data and a major PTCL sales boost will be necessary to jump start investor interest in Allos.
The company conducted a phase IIb, randomised, open-label study of the dihydrofolate reductase inhibitor, comparing it to Tarceva, an EGFr tyrosine kinase inhibitor. Patients studied had stage IIIB/IV NSCLC, had received one or two previous systemic therapies, and were divided into cohorts of light vs heavy smokers, current vs former smokers, squamous vs non-squamous histology, and those who had received previous treatment with Eli Lilly's Alimta vs those who had not. Like Alimta Folotyn, generically known as pralatrexate, is an anti-folate (Event – Positive NSCLC data to drive Allos' Folotyn franchise value, April 22, 2010).
Favourable but unremarkable
Efficacy was most marked in patients classified as light smokers, for whom a 37% reduction in risk of death was observed compared to Tarceva, and those with non-squamous cell carcinomas, with a 35% reduction. Overall, there was a general positive trend, except for squamous patients and Alimta-treated patients, as would be expected. Alimta is not approved to treat the squamous histology.
Although this trial was not considered to be robust enough to generate conclusive data, the results do not seem to demonstrate remarkable superiority over Tarceva. Still, it seems likely that the company will now move into a phase III trial in lung cancer, possibly in a second line setting in patients who have not received Alimta, analysts at Needham believe.
However with Alimta and Tarceva already widely used in a second line setting, strong efficacy will be needed to allow Folotyn to compete.
Tarceva sold $1.2bn last year; three-quarters of the sales were generated in lung cancer, analysts believe. EvaluatePharma forecasts sales of $436m for Folotyn in 2016, whilst Tarceva is anticipated still to be generating revenue at that time of around $1.47bn. Couple this with the ever-present threat of Eli Lilly’s Alimta, also marketed for NSCLC and generating sales of $1.7bn last year, and the question of how Folotyn will move into this market remains.
Worryingly, second quarter results showed sales of $9m for Folotyn in PTCL, below the $10-12m that analysts anticipated. Even bullish analysts are reducing their forecasts in light of these results, and sales in the coming quarters are going to be scrutinised for a pick up.
Further phase II trials are ongoing in non-Hodgkin's lymphoma (NHL), and several solid tumour types, including breast and bladder cancers. Although some analysts muse that Folotyn represents a “pipeline in a product”, others are far less convinced about its potential and consensus forecasts mask very different opinions.
Full data from the lung cancer trial will now be awaited with interest, to better gauge the product's potential.