Dive Brief:
- Diabetes specialist Novo Nordisk's once-daily oral version of semaglutide, sold now as Ozempic in subcutaneous form, has completed its first Phase 3a trial, PIONEER 1.
- The data was analyzed using two different statistical methods, with both showing improvements in HbA1c and weight loss; the greatest improvements compared with placebo were seen with the highest doses.
- Oral semaglutide was safe and well tolerated, with mild-to-moderate nausea that diminished over time as the most common reaction. Nine further PIONEER studies are expected to be completed and reported during 2018, with regulatory submission is planned for 2019.
Dive Insight:
Novo Nordisk and Eli Lilly & Co.'s glucagon-like peptide-1 (GLP-1) drugs are vying for space in the diabetes field.
Lilly's Trulicity (dulaglutide) has been on the U.S. market since September 2014, and its sales have grown from $248.7 million in 2015 to $2 billion in 2017. In November 2017, Novo's Victoza (liraglutide) had a 50% share of the GLP-1 market, with 2017 sales of DKK23.173 million ($3.83 billion).
In the last few months, Novo has added Ozempic (subcutaneous semaglutide) to the mix. It was approved as a weekly injection in the U.S. in December 2017 as an adjunct to diet and exercise to improve glycemic control, and in the EU earlier this month as a monotherapy in patients who can't take metformin, and as an add-on to other antidiabetic drugs.
Clinically, Ozempic has outperformed Trulicity. In a head-to-head 40-week trial in type 2 diabetics, people treated with Ozempic lost more weight and had greater reductions in HbA1c than those treated with Eli Lilly & Co.'s Trulicity (dulaglutide).
The next step in the GLP-1 market battle is Novo Nordisk's once-daily oral semaglutide, which could improve convenience, particularly for needle-phobic patients. In the 26-week Phase 3a study, PIONEER 1, people with type 2 diabetes were treated with three dose levels: 3 mg, 7 mg and 14 mg. There were two different approaches to its analysis.
In the first, using a primary statistical principle required by recent regulatory guidelines evaluating the effect regardless of treatment adherence, people with type 2 diabetes showed significant and superior improvements in HbA1c compared with placebo (the primary objective). Patients taking the highest dose had statistically greater weight loss; the two lower doses also triggered weight loss but it wasn't statistically significant.
In the second, using a secondary statistical principle describing the effect if people had adhered to treatment and did not initiate rescue medication, reductions in HbA1c were 0.8%, 1.3% and 1.5%, respectively, compared to a reduction of 0.1% in people treated with placebo from a mean baseline of 8.0%. Between 59% and 80% of treated patients achieved the American Diabetes Association (ADA) treatment target of HbA1c below 7.0%, compared with 34% on placebo. Weight loss was between 1.7 kg and 4.1 kg, compared with 1.5 kg on placebo.
"We are very encouraged by the results of the PIONEER 1 trial, which confirm the unprecedented oral efficacy of semaglutide that was reported in the Phase 2 clinical trial in type 2 diabetes," said Mads Krogsgaard Thomsen, EVP and CSO of Novo Nordisk.