Physician Views: Clinical evidence continues to build in favour of oral semaglutide

Analyst reaction to a press release issued by Novo Nordisk late on Wednesday indicates the Danish company has released the most promising late-stage clinical data yet for its oral GLP-1 analogue semaglutide; showing superior efficacy and weight loss to both its injectable GLP-1 Victoza and Merck & Co.'s DPP-4 inhibitor Januvia.

To add further perspective, we are snap-polling US and EU5-based endocrinologists to gauge their reaction to the latest data for semaglutide; a product that looks increasingly well positioned to shift the treatment paradigm in diabetes…

Positive headline results have been announced for the Phase III PIONEER 4 study comparing oral semaglutide (a once-daily oral GLP-1) to Victoza (liraglutide). Two statistical approaches were used; a primary method required by regulatory guidance that measured the effect regardless of discontinuation or rescue medication, and a secondary approach that only measured the effect while on treatment and without the use of rescue medication.

Using the primary statistical approach, the primary endpoint of the PIONEER 4 study was met with oral semaglutide demonstrating non-inferiority to Victoza on HbA1c with superior weight loss at 26 weeks.

Using the secondary approach, HbA1c reductions were statistically significant in favour of oral semaglutide and at 26 and 52 weeks were 1.3% and 1.2% compared to 1.1% and 0.9% with Victoza. Weight loss reductions with oral semaglutide were also statistically significant and at 26 and 52 weeks were 4.7 and 5.0 kg compared to 3.2 and 3.1 kg with Victoza. The proportion of people achieving the ADA target of HbA1c below 7% was 69% with oral semaglutide, 63% with Victoza, and 18% with placebo at week 52.

How compelling are these efficacy data for oral semaglutide versus Victoza?

Not compelling

Slightly compelling

Moderately compelling

Very compelling

Extremely compelling

Positive headline results have also been announced for the Phase III PIONEER 7 study comparing oral semaglutide to Januvia (sitagliptin). Using the primary statistical approach, the primary endpoint was met with oral semaglutide demonstrating superiority to Januvia in the proportion of people achieving the ADA target of HbA1c below 7% at week 52 and superior weight reductions compared to Januvia.

Using the secondary approach, patients treated with oral semaglutide experienced a statistically significant reduction in HbA1c of 1.4% compared to 0.7% with sitagliptin at week 52. From a baseline HbA1c of 8.3%, 63% of people treated with oral semaglutide achieved the target HbA1c below 7% after 52 weeks of treatment compared to 28% of people treated with sitagliptin, and the difference was statistically significant. A reduction in body weight of 2.9 kg with oral semaglutide was statistically significantly greater at week 52 compared to 0.8 kg with sitagliptin.

How compelling are these efficacy data for oral semaglutide versus Januvia?

Not compelling

Slightly compelling

Moderately compelling

Very compelling

Extremely compelling

In PIONEER 4, gastrointestinal side effects were similar in patients treated with oral semaglutide and Victoza with nausea rates of 20% and 18%, respectively (versus 4% with placebo). Rates of discontinuation were also similar with rates of 11% for oral semaglutide, 9% with Victoza, and 4% with placebo. In PIONEER 7, 21% of people treated with oral semaglutide experienced nausea, compared to 2% of people treated with sitagliptin. The proportion of people who discontinued treatment due to adverse events was 9% and 3% for oral semaglutide and sitagliptin, respectively.

How compelling is oral semaglutide's safety profile for a GLP-1?

Not compelling

Slightly compelling

Moderately compelling

Very compelling

Extremely compelling

Taking these data into account and assuming oral semaglutide is approved, how do you think its use will be adopted early in the treatment paradigm; i.e. in patients on metformin and ahead of other branded oral antidiabetic treatments?

None

Minimal

Moderate

Significant

Very significant

Taking these data into account and assuming oral semaglutide is approved, how do you think its use will be adopted in more advanced patients already being treated with an injectable GLP-1 or in patients who are candidates for injectable GLP-1 therapy?

None

Minimal

Moderate

Significant

Very significant

Results and related analysis will shortly be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here.

As always, FirstWord would very much like to receive your feedback and suggestions. Note: FirstWord Polls are powered by Medefield MedePolls, a fast-turnaround service to conduct instant polls of up to five questions with guaranteed samples that include physicians from dozens of specialties and over 100 markets. To conduct this poll with a different audience, or an entirely different poll, contact us at info@firstwordpharma.com.

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