Tuesday, February 25, 2014
Wednesday, February 19, 2014
Here is the link to the WSJ article that talks about delivering protein-based drugs directly to intestine.
If you combine this with Afrezza for prandial and Google’s new contact lens for monitoring blood glucose level, you are in diabetes nirvana.
Saturday, February 1, 2014
I was intrigued by the superiority of Afrezza (study 171 results) in reducing Fasting blood glucose levels. Link
There was a significant difference in fasting blood glucose (FBG) levels in the AFREZZA-Gen2 group compared to the insulin aspart group. In the AFREZZA-Gen2 group, mean FBG levels decreased by 25.3 mg/dL by the end of the treatment period whereas the insulin aspart group experienced an increase of 10.2 mg/dL in FBG levels over the same period (p=0.0027). After the four-week follow-up period, during which all patients received insulin aspart and a basal insulin, there was no longer any difference in FBG levels between the treatment groups, demonstrating that this effect on FBG levels was attributable to AFREZZA therapy.
Al Mann provided an explanation in the Q1-2013 earnings call saying "Additionally, in our earlier studies, we have seen reductions in fasting glucose levels, which key opinion leaders say is because AFREZZA lowers insulin resistance."
The article titled “Glucose Toxicity” in Diabetes Care 13:610-30 by Luciano Rossetti, MD, Andrea Giaccari, MD
Ralph A. DeFronzo, MD provides a great explanation.
The abstract is given below.
Glucose toxicity is a well-established entity that has
been shown in animal models of diabetes to contribute
to development of insulin resistance and impaired
insulin secretion. In type II (non-insulin-dependent)
diabetes in humans, a considerable body of evidence
has accumulated indicating that a chronic physiological
increment in the plasma glucose concentration leads to
progressive impairment in insulin secretion and may
contribute to insulin resistance as well. The precise
biochemical mechanism(s) responsible for the
hyperglycemia-induced defect in insulin secretion
remains to be defined but may be related to a defect in
phosphoinositide metabolism. In animal models of
diabetes, development of insulin resistance is related to
down regulation of the glucose-transport system, and a
similar phenomenon is also likely to occur in humans.
In addition, hyperglycemia in humans may lead to a
defect in glycogen synthesis. In this respect, humans
may be different from rats. In type I (insulin-dependent)
diabetic patients who are poorly controlled, insulin
resistance is a characteristic feature and can be
ameliorated by tight glycemic control, suggesting that
hyperglycemia is responsible for the insulin resistance.
Evidence also has accumulated to implicate glucose
toxicity in the functional impairment in insulin secretion
that occurs during the initial presentation of patients
with type I diabetes, and this may explain the
honeymoon period so commonly observed after the
institution of insulin therapy.
Afrezza fits the bill perfectly by providing better PPG control. This in turn reduces glucose toxicity and insulin resistance. The increased glucose uptake reduces the fasting glucose levels.
This article “Role of Reduced Suppression of Glucose Production and Diminished Early Insulin Release in Impaired Glucose Tolerance” also makes similar conclusion.
In conclusion, in persons with impaired glucose tolerance the excessive increase in plasma glucose concentrations after the ingestion of glucose results primarily from excessive entry of glucose into the circulation. This is due to the failure of the liver to reduce its glucose output appropriately and can largely be accounted for by diminished early insulin release and diminished suppression of glucagon secretion. We therefore suggest that insulin resistance in people with more severe glucose intolerance7 , 9 , 10 , 51 may develop as a consequence of more prolonged hyperglycemia (glucose toxicity)5 6 7 , 52 and compensatory hyperinsulinemia.53 In susceptible people, a combination of these factors may ultimately cause further deterioration of beta-cell function and progression to NIDDM.
Saturday, January 11, 2014
An interesting article that is very relevant to the Afrezza approval
Are the FDA’s Endocrinologic and Metabolic Drugs Advisory
Committee (EMDAC) and the Division of Metabolism and Endocrinology
Products (DMEP) in sync?
The article states that EMDAC & DMEP agree only 60% of the time. The article makes an interesting observation that “EMDAC members will spend considerably less time evaluating the available data in comparison with DMEP staff.”
Also if EMDAC was overwhelmingly positive, the FDA followed suit and approved the drug.
Wednesday, January 8, 2014
Thursday, January 2, 2014
Monday, December 16, 2013
Saturday, November 23, 2013
The average market cap to sales is 12.16. Many of the companies in this list do not produce a penny in profit. The market seems to value them based on future prospects. For a mature company like AMGN that produces very little growth in sales, the multiple is very low. The multiple depends on implied growth, pipeline etc. Only the companies trading in US with market cap of more than 2 billion were considered.
This is not a prediction of sales for Afrezza/stock price of MNKD, but just a thought experiment. What would be the future stock price of MNKD, if partner gets 20%?
The table below shows the numbers. This method is not very scientific and ignores dilution risk. What is very clear is that the stock/market cap wont move up without increase in sales.