Interview – Semaglutide holds the key to Novo’s success

Date October 03, 2017

After falling flat with Tresiba, Novo Nordisk desperately needs semaglutide, billed as its biggest growth driver, to live up to expectations. By the end of the year the Danish group could have US and EU approval for its once-weekly GLP-1 agonist, which will be vital for clawing back market share from Eli Lilly.

Novo’s chief science officer, Mads Krogsgaard Thomsen, is confident that the Danish group has the best-in-class agent, but there are reasons to be cautious about the product’s sales potential. One is pricing, with Mr Krogsgaard Thomsen admitting that Novo will only be able to charge a small premium if sema is approved. “We’re not talking about trying to get a 20%, 30% or 40% premium,” he tells EP Vantage.

Another is the fact that, despite a win in the 3,000-patient Sustain 6 cardiovascular outcomes trial, sema is unlikely to get a cardiovascular risk-reduction indication on its label straightaway. “The study was too small,” Mr Krogsgaard Thomsen says. “But we hope to get data in there – which will mean we can go out and tell physicians about it.”

He says Sustain 6 was designed prospectively only to assess non-inferiority and safety, not superiority – nevertheless, it showed a 26% reduction versus placebo in the time to first occurrence of cardiovascular death, non-fatal myocardial infarction or stroke, driven by a 39% decrease in stroke. 

“We underestimated the efficacy of sema,” says Mr Krogsgaard Thomsen. “We expected to be in the 10-15% range, but the event rate was higher than we expected, and the difference was bigger than we expected.”

To support a label expansion, Novo plans to start a bigger CV outcomes trial next year in up to 14,000 patients, which should take around a year and a half to enrol. The group had always expected to carry out this study, he adds, but it is a prime example of the size of the investment Novo is making in sema as it seeks to stay ahead of Lilly, which is taking the market by storm with its rival once-weekly GLP-1, Trulicity.

Franchise building

That investment in sema includes a slew of other studies, including the 10-trial Pioneer programme for a once-daily oral version, due to read out next year. This programme features a head-to-head study against Lilly and Boehringer’s SGLT2 inhibitor Jardiance.

Oral semaglutide phase III trials 
Study  Setting  Data due  Trial ID 
Pioneer 1  Vs placebo in type 2 diabetes  Q1 2018  NCT02906930 
Pioneer 2  Vs Jardiance in type 2 diabetes  Q2 2018  NCT02863328 
Pioneer 3  Vs Januvia in type 2 diabetes  Q2 2018  NCT02607865 
Pioneer 4  Vs Victoza in type 2 diabetes  Q2 2018  NCT02863419 
Pioneer 5  Vs placebo in type 2 diabetes and moderate renal impairment  Q2 2018  NCT02827708 
Pioneer 6  CV outcomes study in type 2 diabetes  2018  NCT02692716 
Pioneer 7  Flexible dose adjustment vs Januvia in type 2 diabetes  2018  NCT02849080 
Pioneer 8  Vs placebo in insulin-treated type 2 diabetes  2018  NCT03021187 
Pioneer 9  Vs placebo or Victoza in Japanese type 2 diabetes patients  2018  NCT03018028 
Pioneer 10  Vs Trulicity both in combination with one oral antidiabetic drug in Japanese type 2 diabetes  2018  NCT03015220 

SGLT2 inhibitors, being oral, tend to be used ahead of injectable products like GLP-1s, but oral sema could change this, Mr Krogsgaard Thomsen believes. “Jardiance by no means matches our GLP-1s, but until we have oral sema they have the benefit of a tablet.”

He is confident of getting a result, stating: “When that reads out I would expect superiority on weight and glucose.” If all goes well oral sema should be launched by 2020, he says.

The injectable version still has around 14 years' patent life remaining, he estimates, while the oral version has slightly longer. This helps explain why Novo is going all in on sema – it is also studying the injectable form in obesity and Nash. In the former the drug works by decreasing appetite, Mr Krogsgaard Thomsen believes: “It’s a specific effect on the brain.”

Obesity is becoming ever more important to Novo as pricing pressure continues to hit the diabetes market, with Mr Krogsgaard Thomsen questioning the wisdom of investing in slightly better diabetes drugs that will not command a premium. “It’s difficult to argue that we should spend billions creating a somewhat better version of Tresiba. It won’t fly,” he says.

A phase II study in obesity recently found nearly 14% weight loss with sema, versus 2% with diet and exercise alone – phase III development is slated to start next year. 

How sema stacks up: top diabetes products in 2022 
          Annual WW sales ($m) 
Rank  Product  Company  Pharmacological Class  Status  2016  2022e  CAGR 
Trulicity  Eli Lilly  GLP 1 agonist  Marketed  926  3,872  27% 
Victoza  Novo Nordisk  GLP 1 agonist  Marketed  2,979  3,295  2% 
Tresiba  Novo Nordisk  Insulin analogue  Marketed  603  2,708  28% 
Januvia  Merck & Co  DPP IV inhibitor  Marketed  3,908  2,672  -6% 
NovoRapid  Novo Nordisk  Insulin analogue  Marketed  2,964  2,509  -3% 
Semaglutide  Novo Nordisk  GLP 1 agonist  Filed  2,422  n/a 
Lantus  Sanofi  Insulin analogue  Marketed  6,322  2,390  -15% 
Humalog  Eli Lilly  Insulin analogue  Marketed  2,769  2,020  -5% 
Toujeo  Sanofi  Insulin analogue  Marketed  718  1,826  17% 
10  Janumet  Merck & Co  DPP IV inhibitor & biguanide  Marketed  2,201  1,777  -4% 
25  Semaglutide Oral  Novo Nordisk  GLP 1 agonist  Phase III  707  n/a 
DPP: Dipeptidyl peptidase; GLP: Glucagon-like peptide. Source: EvaluatePharma. 

Sema’s molecular structure means that it can cross the blood-brain barrier more easily than Novo’s older GLP-1 agonist Victoza, according to Mr Krogsgaard Thomsen. As well as potentially improving its efficacy in obesity, this might also make sema useful in Alzheimer’s or Parkinson’s diseases. "If academics can help us show an effect, we would embrace it.”

Meanwhile Trulicity is a “huge molecule” so cannot get into the brain, he says. “This is why sema showed twice the weight loss versus Trulicity in Sustain 7.”

However, Lilly is a formidable opponent, and Trulicity is still forecast to be the biggest diabetes therapy in 2022, according to EvaluatePharma sellside consensus, despite being beaten by sema in Sustain 7 (Novo and Lilly head for diabetes pricing battle, August 18, 2017).

“In my view it’s us and Lilly competing. We are stronger on the GLP-1 and insulin side; they are strong because of the breadth of their portfolio,” says Mr Krogsgaard Thomsen.

“Lilly is overtaking Sanofi as the world’s number-two diabetes company – but they’re not going to overtake us.” Novo needs sema to deliver if it wants to keep it this way.

Top-three diabetes players 
Company  Sales ($bn)  Market share  Market rank 
  2016  2022e  CAGR  2016  2022e  2016  2022e 
Novo Nordisk  14.3  18.7  5%  25.9%  27.7% 
Eli Lilly  5.6  8.7  8%  10.2%  12.9% 
Sanofi  8.2  6.6  -4%  14.8%  9.8% 
Source: EvaluatePharma. 

To contact the writer of this story email Madeleine Armstrong in London at madeleinea@epvantage.com or follow  @ByMadeleineA on Twitter

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