'Oral insulin medicines can hardly replace injections'

Korean endocrinology physicians agreed that oral insulin preparations under development by Oramed Pharmaceutical would not be able to replace existing insulin injections.

They expressed the view during a press briefing where Oramed and Medicox, a local pharmaceutical company, announced the clinical status of ORMD-0801, an oral insulin candidate from Oramed Pharmaceuticals. Medicox has exclusive Korean distribution rights for ORMD-0801.

Oramed used its protein oral delivery (POD) platform for ORMD0801 so that the enteric-coated tablet capsule to reach the intestine.

The company also used protease inhibitors in the capsule to protect it from proteolytic enzymes. According to Oramed, ORMD-0801 mimics endogenous insulin in the liver and releases it into the bloodstream. Unlike conventional insulin injections, it does not increase weight and improves the ease of treatment.

Oramed CCO Michael Rabinowitz stresses the strength of the company’s oral insulin candidate at a news conference held at Josun Palace Hotel in Seoul on Thursday.

"Insulin injections go directly into the bloodstream, and only a small amount of insulin reaches the liver," Oramed CCO Michael Rabinowitz said. "It does not follow the body's natural physiological mechanisms."

However, Oramed's oral insulin candidate has several advantages by acting through the hepatic portal vein, and the company has confirmed the drug's safety profile, Rabinowitz added.

Rabinowitz stressed that the advantages of oral insulin do not lie only in patient convenience.

"Oral insulin not only increases the convenience of taking it but is also a great help for those who do not know how to give an injection," Rabinowitz said. "The biggest advantage of oral insulin is glucose control."

The Oramed CCO explained that several types of research show that quite a few doctors are taking a favorable stance on oral insulin administration.

"Likely, doctors' perceptions will also act as a favorable factor in implementing the commercialization plan in the future," he said.

However, in contrast to Oramed's expectations, Korean doctors participating in the conference suggested that Oramed's oral insulin will be a new treatment option that can resolve some of the existing problems but will not be able to replace existing injectable insulin drugs.

"Looking at the data, I saw that ORMD-0801 is an oral insulin drug that targets the liver," Professor Kim Jae-hyun of the Department of Endocrinology at Samsung Medical Center said. "Therefore, it is important not to misinterpret Oramed's oral insulin candidate as a substitute for insulin injections for patients who need subcutaneous injections or who have very low insulin."

Professor Kim Seong-rae of Bucheon St. Mary's Hospital also agreed.

"Based on the action standard of oral insulin preparations, it is appropriate to understand the role of supplying additional necessary insulin while taking insulin injections rather than completely replacing existing insulin injections."

Oramed officials also explained some concerns regarding the development of oral insulin.

Oral insulin preparations are treatments that even multinational pharmaceutical companies, such as Novo Nordisk, have failed to develop due to solving low permeability through the membranes of the intestine due to large molecular weight and hydrophilicity.

While Oramed is using a protease inhibitor and absorption enhancer to overcome the limits of oral insulin, there have been concerns that while safe in the short-term, the protease inhibitor and absorption enhancer still need to be properly verified regarding long-term safety.

"With the Oramed technology, we have proven the tolerability and safety of oral insulin preparations," Rabinowitz said. "Even considering the use of protease inhibitor and the absorption enhancer, there were no special issues, and although safety for long-term use is important, there were no signals that would cause problems."

Rabinowitz added that the company plans about the spike in the oral insulin price as it needs to use a larger dose of insulin than an insulin injection.

Previous developments of oral insulin made by other companies discovered it is hard to maintain glycemic index levels when using the same insulin dosage as an injection.

Industry watchers have questioned the dosage of Oramed's oral insulin compared to insulin injections, as an increase in insulin dosage would mean a spike in price, which may make the treatment less favorable to both physicians and doctors.

"We had no choice but to increase the dose to prove the drug's effectiveness," Rabinowitz said. "We also acknowledge concerns that If the price is too high, patients will not be able to use the treatment."

Oramed is working with various partners to develop a price tag that can benefit everyone. Rabinowitz added that when discussing with Medicox and Korean regulatory authorities, the company will adjust the price so Medicox can provide the treatment at a reasonable price while also making a profit.

The company is conducting two phase 3 clinical trials in the U.S. for ORMD0801.

The first phase 3 trial is a study on 675 people with type 2 diabetes and taking at least one to three oral hypoglycemic agents. The primary endpoint is to compare the efficacy of ORMD-0801 with a placebo in improving glycemic control as assessed by a diabetes test. The secondary endpoint is a change in fasting plasma glucose at 26 weeks.

The second phase 3 trial is a study on 450 patients with inadequately controlled type 2 diabetes on diet modification alone or diet modification plus metformin alone. The primary endpoint was 26 weeks, and the secondary was to compare ORMD-0801 and placebo for the degree of maintenance of glycemic control over 52 weeks.

Oramed plans to release the top-line results of the first phase 3 clinical trial in January next year.

However, releasing the top-line results does not mean Oramed can launch the drug anytime soon.

"In addition to the first phase 3 clinical trial, approval will only be obtained when the results of the ongoing second phase 3 clinical trial for initial use are released," Rabinowitz said. "Assuming that both are successful, considering the preparation of documents and other procedures, we expect the drug launch will take about two years to two years and a half."