Mannkind’s (NASDAQ:MNKD) tribulations with its inhaled insulin Afrezza do not seem to have put off other groups trying to develop novel methods of delivery. But it looks like it will take a little while longer to get an oral product to the market after disappointing phase II results from Midatech (NYSE:MTP) and Oramed (NASDAQ:ORMP) (see table below).
Midatech’s data were unequivocally negative, with its MTD101 showing low bioavailability versus subcutaneous insulin, sending its stock down 14% yesterday. The picture with Oramed’s ORMD-0801 was less clear: the company said its trial met its primary endpoint but refused to give more detailed data, leading to skepticism over the results.
Oramed’s share price initially rose 25% yesterday, but ended up closing down 8%.
Reverse Midas touch
Midatech says it will “evaluate strategic options” for MTD101 with its partner MonoSol Rx, but surely the project – a dissolving film that is placed on the inside of the cheek – is dead in the water.
Oramed, meanwhile, seems determined to push on into phase III, saying it was looking for strategic partners. Any interested parties might want to wait for the presentation of full results, as the company would only say that insulin-treated patients showed a significant difference in night-time mean glucose levels, pooled across two doses.
Glucose levels were 6.5% lower in the pooled treatment group versus placebo, and Oramed says this hit statistical significance with a p value of 0.0268. But on a conference call to discuss the results the company refused to break out the results for the separate insulin doses of 16mg and 24mg.
Michael Berelowitz, head of Oramed’s scientific advisory board, said the company would “share the information when we have it”.
He added that it was difficult to speculate on whether the reduction in glucose levels was clinically meaningful, and if it would translate into an effect on HbA1c levels.
“Yesterday, if you’d asked how oral insulin works, you would have said it doesn’t. Today, we can say that oral insulin actually works,” he replied in response to the question on HbA1c.
Oramed and Midatech are not the first to try to develop new methods of insulin delivery. Oral insulin promises greater convenience over the current standard of care, subcutaneous injection, and could improve compliance and allow therapy to begin at an earlier stage of disease than is currently the case, potentially leading to better outcomes.
But oral delivery is particularly tricky because, being a peptide, insulin is degraded in the gastrointestinal tract before it can reach the bloodstream.
Novo Nordisk seems to be the most active company in this field, with one asset in phase II and another in phase I. However, it also has four abandoned projects to its name, according to EvaluatePharma.
The only other delivery method to get approved so far is inhaled insulin, though Pfizer's (NYSE:PFE) Exubera and Mannkind’s Afrezza were commercial disasters (Fighting over Mannkind’s corpse, January 6, 2016).
This means there is still room for oral insulins if the technical barriers can be overcome. “In the history of orally delivered insulin, many have tried and few succeeded,” said Oramed’s Mr. Berelowitz. It is still far from clear whether the company is one of the success stories.
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