Welcome to Pipeline Review

Generex Biotechnology, and their wholly owned subsidiary Antigen Express, are developing promising new drugs to treat diabetes, as well as synthetic peptide vaccines targeting HER2/neu cancer and pandemic flu. The flagship product for Generex is Oral-lyn buccal insulin. Antigen Express' leading vaccine is the AE37 HER2/neu synthetic peptide vaccine to prevent breast cancer recurrence. I am not qualified to offer investment or medical advice, and make no claims that I am an expert in these areas. I am a layman and a shareholder in this company. The left side of Pipeline Review holds blogs regarding Generex and Antigen Express, while the right side offers items of due diligence mixed with my analysis which may be of interest to others seeking to learn about Generex's pipeline. If the left side only shows the latest blog, click on the word home to view them all.

Search This Blog

Thursday, March 11, 2010

Type 2 Diabetes Drugs: Treating One Disease by Causing Another?

The Food and Drug Administration (FDA) will reveal on Friday the fate for a once-weekly form of the popular diabetes drug Byetta. Eli Lilly, Amylin Pharmaceuticals and Alkermes are collectively developing the drug, named Byetta LARS. LARS stands for long acting release formula. Patients treated in clinical trials with the once-weekly formulation showed a statistically superior reduction in blood sugar than those taking standard Byetta. Byetta is currently approved as a twice daily injection option for Type 2 diabetics and has annual sales of about $700 million.

In January, the FDA approved the new diabetes drug Victoza, developed by Novo Nordisk. Victoza is in the same class as Byetta, called GLP-1 receptor agonist. These drugs are designed to slow glucose absorption in the gut. This allows a Type-2 diabetic’s slow insulin response to catch up. The GLP-1 agonist class also attaches to an appetite receptor in the brain and decreases hunger, leading to weight loss in patients. However, there have been some reports of other side effects for GLP-1 that are far less appealing than lower blood sugar levels and weight loss.

Byetta has been publicly linked to cases of severe pancreatitis since mid-2008. Byetta has been prescribed to millions, and these cases represent a small fraction of them, but the FDA has alerted healthcare professionals. Eli Lilly and Amylin have defended Byetta's safety track record, but that has become more difficult since the FDA has also now warned health care professionals that Byetta had been possibly linked to kidney problems, including renal failure. Again, this was an overall small percentage of users, but this has resulted in the long-acting version of Byetta being feared, rightly or wrongly, to the same problems. An additional emphasis may be made since it will be in a patient’s system for a full week.

The FDA's approval of Victoza, administered as a once-daily injection, has led to speculation that Byetta LARS will clear its last major regulatory hurdle. In clinical trials pancreatitis occurred more often in patients who took Victoza than in patients taking other diabetes medicines. That does not sound like a clinical trial endpoint that the FDA should find appealing. In animal studies, Victoza caused tumors of the thyroid gland in rats. The FDA approval of Victoza came with a Black Box warning regarding the drug's thyroid tumor risk. Of course, that wouldn't comfort a diabetic who gets his blood sugar under control only to find out he has thyroid cancer. If these drugs present risks that are unknown, than the FDA should require longer testing.

Recently, the Senate Finance Committee issued a 334 page report which concluded the findings of a two-year investigation after a 2007 study published in the New England Journal of Medicine reported a link between Avandia and heart attacks. The 334-page report by the Senate Finance Committee criticized the FDA, stating that agency overlooked or overrode safety concerns found by its staff. According to the Senate report FDA scientists estimated in July 2007 that Avandia was associated with approximately 83,000 heart attacks since the drug came to market.

The report highlighted other damning decisions by the FDA. In 2007, a FDA panel recommended by a vote of 22-1 that Avandia should remain on the market despite an analysis showing links to increased risk of heart attack. The vote was not binding, but a suggestion to FDA regulators. At the same meeting the panel also voted 20-3 in support of data that showed Avandia increased the risk of cardiac ischemia in patients with the most common type of diabetes. However, even in 2010 the decision making process of the FDA in regards to Avandia continues to bewilder.

Just after the senate report was made public the FDA stated that patients should not stop taking the diabetes drug. Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, said during a teleconference with diabetes doctors that the FDA feels "it is time for a thorough evaluation of all the cardiovascular risks with that drug". They apparently are in no rush since they planned an advisory panel meeting in July and the drug remains on the market. We find out tomorrow if the Type 2 diabetes market grows more crowded with drugs that not only treat their disease, but potentially cause another.

With the FDA already well extended past the original PDUFA date for Mannkind's inhalable insulin, we can expect another decision soon concerning their new drug that also comes with questions that long term usage may have on the lungs. I believe that the latest news released by Generex Biotechnology, concerning the FDA Treatment IND for Oral-lyn buccal insulin, gives me hope this simple spray can fill the need of Type 2 patients who may be wary of all the controversial drugs their doctors and federal regulators push their way.

Byetta, Byetta LARS, Victoza, Avandia, or Actos; none of them are insulin. Nothing is as effective as controlling blood sugar levels as insulin, and the problem is getting Type 2 diabetics to consider initiating insulin therapy into their routine. When that problem is solved, the giant market for all of these other options will subside. With no serious safety issues to date for buccal insulin, diabetics may feel confident that their medicine is not causing additional illness. In time, diabetics and physicians may find Oral-lyn to be the simplest of solutions.