AstraZeneca’s (NYSE:AZN) efforts to expand its EGFR inhibitor franchise are on track, with its third-generation project Tagrisso set to overtake Iressa next year. Data just reported in second-line non-small lung cancer should put a rubber stamp on last year’s accelerated approval – and there could be more to come (see tables below).
A phase III read out in first-line NSCLC is expected next year. If positive and approval in the first-line setting follows, sell-side forecasts would increase accordingly – Leerink analysts have already said they would up their 2026 peak sales prediction from $3.5bn to $6.4bn.
Leerink’s forecast is an indication of just how much Tagrisso’s prospects have improved – even the current number outstrips chief executive Pascal Soriot’s bullish $3bn peak sales projection when Astra was fending off Pfizer’s (NYSE:PFE) takeover bid (Don’t blame Soriot, he’s just doing his job, May 7, 2014).
Iressa was one of the early personalized medicines and Astra has taken the same approach with Tagrisso by targeting those with EGFR T790M mutations, which are present in roughly 10% of NSCLC patients in the US and 35% in Asia.
The product received accelerated approval last year in patients who had progressed on or after another EGFR tyrosine kinase inhibitor, with continued approval dependent on confirmatory clinical trials.
The latest study, called Aura3, should make this a formality. It found that Tagrisso improved progression-free survival by 5.7 months versus chemotherapy; PFS was 10.1 months and 4.4 months respectively, a statistically significant difference with a p value of less than 0.001.
The data, presented at the World Conference on Lung Cancer in Vienna and simultaneously published in the New England Journal of Medicine, mark the first time a targeted medicine has shown an improvement in PFS over standard platinum-pemetrexed chemotherapy according to the lead investigator, Vassiliki Papadimitrakopoulou from the University of Texas MD Anderson Cancer Center.
Astra hopes the results could help Tagrisso become the new standard of care in patients who have progressed after earlier-generation EGFR tyrosine kinase inhibitors.
Forecasts for Iressa have been falling for the last couple of years and the product is set to lose patent protection in 2017.
But Tagrisso seems well placed to take over – it was one of the bright spots in an otherwise lackluster third quarter for Astra. Sales of the product in the first nine months of 2016 totaled $276m, not too far off Iressa’s $395m.
Tagrisso has been helped by the downfall of Clovis Oncology’s rival EGFR inhibitor rociletinib, but the latest data cannot hurt either.
And there are already hints that Tagrisso might outperform earlier-generation EGFR inhibitors in first-line disease. The phase I Aura trial found a PFS of 19.3 months, which compares favorably to around 11 months seen with Iressa, Roche’s (OTCQX:RHHBY) Tarceva and Boehringer-Ingelheim’s Gilotrif, although the usual caution about cross-trial comparisons applies.
This improved response might be explained by its specificity for the T790M-mutated EGF receptor. Astra and its investors will be watching to see if this impressive result is confirmed in the Flaura phase III study.
Tagrisso has steadily become one of Astra’s most important assets and is now forecast to be its second-biggest seller by 2022 – up from fourth place last time this analysis was carried out (Event – Astra still hopes for brilliance with Brilinta, September 15, 2016).
Astra has various problems to contend with but, at the moment, Tagrisso is not one of them.