First let me say I think its great that progress is being made on oral administration of Insulin. I believe ORMD with its liver first pass metabolism mechanism of action is making progress. However:
was reached at an approximate 100-min lag from start of meal
(Table 1, range: 60-150 min),
In all cases, insulin levels returned to baseline within 45-300 minutes of peak recordings,
ORMD-0801 offers no advantage in pharmacodynamics over afrezza what so ever. (afrezza cMAX 12 minutes, clearance 90 minutes) Though much has been made to compare Afrezza and ORMD-0801 there only similarity is that they are an alternative to needle injections. Its obvious to me that ORMD-0801 will in fact become the needle alternative for long acting insulin administration. Together MNKD and ORMD will offer the only completely needle free treatment of diabetes. In short MNKD and ORMD will never be in direct competition because MNKD is far superior in its pharmacodynamics for meal time insulin.
I agree. The oral insulin will never be the first line treatment such as afreeza to treat type2. it will be an adjunct. It simply can't control blood glucose on its own. it will still be subject to hypo or hyper glycemic events. I believe it's an approvable medication and it has a market but it won't compete with mnkd but will work with it.
Perhaps Mnkd buys our ORMP? Money will soon be flowing into mnkd's coffers. I would think it's a smart buy.
Do you agree that there could be some cross-over for Type 2 folks that today would not be on insulin, but would be prescribed Afreza or ORMD-0801 as a maintenance program. in future to stave off Type 2 progression? That is the only threat I see - but again, YEARS from now, not any time in the next 3-5 years as Afrezza builds its base of users.
Yes I completely agree that early type II phenotype is the most likely area of success for ORMD-0801, but its lack of bioavailibility will make it expensive compared to lantus or RAA's or Afrezza. I think people under-estimate how important bioavailibility is for the ultimate cost of an insulin product.
Insulin / Humalog production
The plant consists of five operational suites. The first is the media preparation area where the bulk media is formulated before inoculation and up-filling to the pre-fermentation vessels to begin the fermentation. The second is the fermentation suite (consisting of three 15,000L bioreactors) and associated storage tank farm.
The third is the pre-purification area where the Escherichia coli are killed and broken down (lysed) to harvest the pre-proinsulin. The pre-proinsulin is separated out from the cell debris by centrifugation and filtration.
The fourth area is the refolding suite where the pre-insulin is treated with buffers to assist it in attaining its tertiary structure. The pre-proinsulin may still be attached to other peptides added to it by the E. coli so further purification is required.
The final area is the downstream purification suite where the pre-proinsulin is cleaved using trypsin to modify its primary structure and then separated by chromatography and finally crystallised.
The chromatographic process is monitored by protein-specific analysis using enzyme-immunological methods that make it possible to detect even the smallest possible by-products. The purity of the insulin is measured at every intermediate stage of production by the In Process Control (IPC) laboratory.
The product insulin (lispro) can then be used to formulate Humalog, which is a mixture of insulin lispro and insulin lispro protamine.
**** How would you like to lose 92% of your final product due to poor bioavilibility??
I have looked for that information. I have not been able to find anything concrete on the subject. Scientifically I would speculate that its a hexamer encapsulated and delivered to the gut while a monomer is delivered after first pass metabolism in the liver. One of the hallmarks of insulin monomers is their relative instability which only Afrezza has successfully stabilized with the technosphere technology.
“This one doesn't look like it's going anywhere as a rapid-acting insulin, but it might actually work as a basal insulin, given orally,” Dr. Skyler said.
Another important factor which will greatly inhibito ORMD-0801 from commercial success compared to AFREZZA:
ORMD-0801’s bioefficiency (the relative activity per dose of the orally delivered insulin compared to subcutaneous injection) is estimated by Oramed to be in the 5-8% range, based on measurements of glucose reductions in comparison to subcutaneously administered insulin in healthy volunteers. This figure is relatively low compared to few published results from other oral insulin products, although models and measurement methods usually differ among the publishing sources. The single digit oral bioavailability of ORMD-0801 is comparable to other oral insulin products in development.
This will make the cost of production for ORMD-0801 huge when compared to Afrezza which has 60% bioavailibility.
Its not cheap to produce a biologic like Insulin. The greatest cost factor is production. As I stated before the future of ORMD is in long acting insulin if at all.