Clinical trials ongoing in diabetes this year could provide the basis for foundational change in the way the disease will be treated in the next decade. Here are three to watch in 2018 and how they may affect the diabetes market going forward into the 2020s.
Novo Nordisk and Oral Semaglutide
Semaglutide is a GLP-1 analogue that stimulates the pancreas to produce insulin in type II diabetes patients. As of now GLP-1 drugs are only adminstrable by injection. Novo Nordisk A/S (NVO, Financial) developed semaglutide as a next-generation Victoza (liraglutide). Victoza is a once daily injectable GLP-1 analogue that sold $3 billion in 2016, putting it among diabetes bestsellers. Semaglutide is a longer-acting once weekly injectable, making patient compliance much easier. It just got FDA approval last month under the trade name Ozempic, and Novo’s efforts to improve the drug continue with an oral formulation.
Several Phase III trials are now ongoing. In fact nine are listed on clinicaltrials.gov. These trials follow a successful six-month Phase II study of 632 patients. Patients were given oral or subcutaneous semaglutide or placebo for 26 weeks with a 5 week follow up. HbA1C levels, which measure average blood glucose over 90 days, dropped in a dose-dependent manner for the oral arm, and the highest dose cohort matched the 1.9% drop in the subcutaneous arm. HbA1C levels dropped only 0.3% for placebo. Weight loss was similar in both semaglutide arms oral and subcutaneous, both greater than placebo, and safety was similar across all arms.
If these results can be repeated in the ongoing Phase III trials this year, we could see the first oral GLP-1 analogue on the market by the end of the decade. If it proves as effective as injectable formulations, the market for these drugs could shift significantly towards oral.
Oramed and Oral Insulin
Novo Nordisk is not alone in its pursuit of an oral diabetes drug that is currently only available by injection. Oramed Pharmaceuticals Inc. (ORMP, Financial) will be initiating a Phase IIb trial for its oral insulin candidate ORMD-0801 this quarter. A previous Phase IIa trial showed reduction in fasting, daytime, nighttime, and 24-hour glucose levels, and also showed a statistically significant reduction in HbA1C levels over 28 days. What the Phase IIb trial hopes to show is a meaningful reduction in HbA1c levels over a full 90 days, which will give investors a better idea of whether the drug can make it past Phase III.
A lowering of HbA1C is the gold standard endpoint for all insulin candidates in Phase III trials, so ORMD-0801 will have to show significant reduction in this measure if it is going to succeed in a pivotal trial planned for 2019. If the Phase IIb succeeds, the diabetes community might start taking the possibility of oral insulin, after a century of failed attempts, more seriously.
Oramed doesn't seek to replace injectable insulin with oral, but does hope that oral insulin can be prescribed at earlier stages of the disease so that less insulin is required as the disease progresses.
Eli Lilly and Ultra Rapid Insulin
There is only one ultra rapid insulin in the market right now, and that is Novo Nordisk’s Fiasp, projected to sell $500M annually by 2020. Fiasp was approved in September and is the only insulin that can be taken between 2 minutes before and up to 20 minutes after a meal. The fact that it can be taken so close to a meal makes compliance easier because patients don’t have to plan an injection prior to a meal.
Eli Lilly and Company (LLY, Financial) is responding with an ultra rapid insulin of its own, LY00014, which is being tested in two Phase III trials this year, one for type I and one for type II diabetes patients. Both trials are expected to be completed this year.
These will be critical for Eli Lilly because its current #1 moneymaker is Humalog, a fast-acting insulin that LY900014 is looking to supplant. In order to maintain or grow its current diabetes market, Eli Lilly will need to compete with Fiasp with its own ultra-rapid insulin or risk losing market share to Novo Nordisk.
Disclosure: Long NVO, ORMP
