Lilly’s Protomer deal shows innovation in diabetes is not dead

Lilly and Novo look set for a battle in glucose-sensitive insulin, and other areas too.

Diabetes might not seem like the most dynamic sector, but Lilly and Novo clearly still see room for growth. The former yesterday acquired Protomer Technologies to get its hands on a glucose-sensing insulin project, an area in which its Danish rival is already active.

Lilly’s move sets up a battle here, and a look at the groups’ respective diabetes pipelines shows that there are various other mechanisms over which they soon could be vying.

The idea behind glucose-sensitive insulins is that they can switch on when patients’ blood glucose levels rise, and switch back off again when levels return to normal, thereby providing better glycaemic control and reducing the risk of hypoglycaemia.

Novo looks to be slightly ahead, with its project already in phase 1. The asset, which the Danish group gained with the takeover of Ziylo in 2018, comprises glucose-binding small molecules linked to insulin.

Lilly obviously believes that this is an area it needs to compete in: the up-front value of the deal was not disclosed, but the tie-up could be worth over $1bn if all goes well.

Still, this is not the most immediate battleground for the two groups, the table below shows.

Diabetes: the next generation. New battlegrounds for Lilly and Novo
Description Lilly project & status Novo Nordisk project & status
GIP/GLP1 Tirzepatide, filing due 2021 NN9389 (once-weekly SC sema + NNC0480-0389), ph1
Once-weekly basal insulin Basal insulin FC/LY-3209590, ph2 in T2DM (insulin- experienced & naive) & T1DM Insulin icodec/LAI287, ph3 Onwards 1, 2, 3, 4, 5 & 6
GGG tri-agonist LY3437943, ph2 in T2DM & obesity Discontinued
Oral GLP1 LY3502970, ph1 Rybelsus, approved
PYY analogue Ph1 PYY 1875, ph1 in obesity
Glucose-sensitive insulin Protomer project, preclinical NN1845, ph1 
Source: Evaluate Pharma &

The next big race is for a once-weekly insulin. Again Novo is in the lead, with the phase 3 Onwards programme with its candidate, insulin icodec, set to yield data next year. Meanwhile, Lilly recently reported results from a phase 2 study of its project, basal insulin Fc or Bif, with pivotal development not slated to start until 2022.

Lilly’s vice-president of diabetes and metabolic research, Ruth Gimeno, played down the group’s lagging position during a recent investor event tied to the American Diabetes Association conference.

She said that Bif could have the flattest pharmacokinetic profile among the basal insulins, which should lead to decreased glycaemic variability and a lower risk of hypoglycaemia. Lilly will have to hope that, if true, this will compensate for its latecomer status.

Dual duel

One area in which Lilly certainly has not been late to the party is dual GIP/GLP1 agonism: here, the group is planning a 2021 filing for tirzepatide, earmarked by the sellside as big pharma’s most valuable R&D project.

Novo is well behind here, with a combination of its marketed diabetes drug semaglutide plus a once-weekly GIP agonist in phase 1. 

And Novo is not even involved in the GIP/GLP2/glucagon tri-agonist space, having ditched this mechanism last year. While GLP1 and GIP are thought to have a role in appetite suppression, glucagon can increase energy expenditure, providing another potential route to enhance weight loss.

However, other mechanisms that increase energy expenditure have caused problems in the past, and Novo has previously hinted that serious toxicity concerns were behind the termination of its tri-agonist, as well as a glucagon/GLP1 dual agonist.

Lilly has not flagged any serious side effects with its GGG tri-agonist, saying that in phase 1 the project's side-effect profile was consistent with those of GLP1 agonists. Investors will no doubt be keeping an eye on safety when phase 2 trials yield data next year.  

Lilly also hopes to play in the oral GLP1 monotherapy space, despite the fact that Novo already has an approved product here in the shape of Rybelsus. However, that drug must be given at least 30 minutes before the first food or drink of the day, other than a small amount of water.

Lilly believes that its contender, LY3502970, might not require such food and water restrictions.

The group is also developing oral GIP/GLP1 agonists and one, LY3493269, is already in the clinic; another phase 1 project, LY3537031, could also be formulated for oral use.

A wild card in this space could be PF-06882961, an oral GLP1 being developed by Pfizer, which is set to yield phase 2 data this year.

But Lilly and Novo are the big diabetes players and, judging by recent moves, will continue to be for the foreseeable future.

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