Nine down, one to go for oral sema


The positive-ish top-line data on Novo Nordisk’s oral form of semaglutide released yesterday means that nine of the 10 Pioneer trials have read out broadly in favour of the pill. Pioneer 9, conducted in 243 Japanese people with diabetes, showed that at six months all three doses of the GLP-1 permitted a statistically significantly greater reduction in HbA1c than placebo; the highest dose, 14mg, also beat fellow GLP-1 Victoza on this measure, at 1.7% vs 1.4%. Body weight reduction, measured at one year, was 2.8kg with the highest dose, making this statistically superior to both placebo (1.0kg) and Victoza (a weight increase of 0.4 kg). The other doses were not statistically better. With Pioneer 8 having come out positive across the board last month, just one of the Pioneer trials has yet to report – the largest and most important, Pioneer 6. This is the cardiovascular outcomes trial, and though large by oral sema’s standards it is not clear that it is large enough to show a cardioprotective effect for the pill. Novo’s wait continues.

Oral semaglutide phase III trials   
      Results (intent-to-treat basis)  
Study  Setting  N HbA1c reduction Weight loss Trial ID 
Pioneer 1  Vs placebo  703  Statistically superior for all 3 doses Superior for highest dose only* NCT02906930 
Pioneer 2  Vs Jardiance  816  Statistically superior Not statistically superior** NCT02863328 
Pioneer 3  Vs Januvia  1,860  Superior for highest 2 doses Statistically superior for all 3 doses NCT02607865 
Pioneer 4  Vs Victoza  690  Non-inferior*** Statistically superior NCT02863419 
Pioneer 5  Vs placebo; moderate renal impairment   324  Statistically superior Statistically superior NCT02827708 
Pioneer 6  CV outcomes  3,176  Data due Q4 2018 NCT02692716 
Pioneer 7  Flexible dose adjustment vs Januvia  500  Statistically superior Statistically superior NCT02849080 
Pioneer 8  Vs placebo in insulin-treated patients  720  Statistically superior Statistically superior NCT03021187 
Pioneer 9  Vs placebo or Victoza; Japanese patients   240  Statistically superior for all 3 doses vs placebo; highest dose superior vs Victoza Highest dose statistically superior vs placebo and Victoza NCT03018028 
Pioneer 10  Vs Trulicity, combination study in Japanese patients  455  Statistically superior for highest dose Statistically superior for highest dose NCT03015220 
*Numerical superiority on a per-protocol basis for all 3 doses; **statistical significance hit at 52 weeks, but not at 26 weeks; ***numerical superiority on a per-protocol basis.

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