Just a couple of months after Novo Nordisk shook up the big diabetes market with the arrival of its GLP-1 drug Ozempic (semaglutide) in the US, the big Danish company has begun rolling out the first in a long lineup of Phase III studies for its next-gen oral version of the drug. And the debut of the Phase III data started out on a positive note.
Researchers for Novo say that the first of 10 Phase III studies that read out this year came with statistically significant results on all three doses tested. And if they can stay on track, they plan to field the first ever oral GLP-1 to regulators in 2019, vowing to command an even bigger share of the mega blockbuster market after overcoming some huge hurdles in developing an oral peptide therapy.
Here’s the breakdown. Novo tested three doses in this first study: 3, 7 and 14 mg.
Those three doses produced reductions in HbA1c of 0.8%, 1.3% and 1.5%, pushing diabetics below the critical 7.0% mark by 59%, 72% and 80% of patients. And they lost weight, averaging cuts of 1.7 kg, 2.5 kg and 4.1 kg — though only that high dose response was statistically significant.
Eli Lilly is already manning the defenses in the battle for market share involving the injectable GLP-1s, with Novo coming at them with data to prove that semaglutide is better than Trulicity. And analysts are now paying rapt attention to these new oral data points. If Novo can achieve roughly the same responses with a pill to replace an injection, they feel that they can more effectively yank away patients from Eli Lilly.
But it’s not an easy task. Researchers have been working on oral peptides for years, often defeated by the storm of caustic enzymes and acids that the body uses to absorb food, which leaves little bio-availability left.
In Novo’s case, they are way out front with a drug that requires patients to avoid eating breakfast for about half an hour after they take the pill. But they believe it can still work with patients.
Lilly execs, though, have been scoffing at the pills, saying they’re a crude attempt that offers an inferior solution to diabetics.
At the high dose, noted Lilly’s top scientist Jan Lundberg a couple of weeks ago, peptides are hindered “by a lot of natural mechanists, and we assume that the Novo product only has 1 or 2% bio-availability, which means that you lose most of the substance. The dilemma also remains here about the need for having fasting and not eating for some time after you take this drug, because then you have food interactions, so it’s really a suboptimal oral agent. I think it would be so much better to have a more traditional small molecule for this receptor.”
And that’s what they’re working on now, though the drug is still in preclinical research, far behind the Novo work.
Analysts are also keenly following the side effects of this drug, particularly the nausea that has been cited before. Evercore ISI’s Umer Raffat noted:
We didn’t get full details by arm, but press release notes 5-16% of pts had nausea vs 6% in pbo. To me, this suggests lower doses are pbo-like. And the 14 mg dose likely tracked in the mid-teens. It’s higher than pbo, but imho, manageable. Again, even this nausea issue ties back to Pk management via stringent pre- and post-dose fasting period and volume of water etc.
Novo Nordisk has been a dominant player in the diabetes market for years, with a sharp and professional R&D group well known for hammering away at scientific problems until they are mastered and new drugs can be marketed.
This group won’t back down, but neither will Lilly.
“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 II clinical trial in type 2 diabetes,” said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. “We look forward to providing data from the remaining nine PIONEER trials throughout this year and an expected regulatory submission in 2019.”
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