A Tale of Two Insulins and a Lot of Lawyers

I read recently about two insulins where the lawyering has gotten pretty intense. One is the sad tale of a me-too insulin that just got approved in the United States, but can't be sold here, and the other is an insulin delivery system that's not approved in the U.S., but which you apparently can buy in Equador, Algeria, and Lebanon. And previously could also get in India.

First, the insulin that's approved but can't be sold. A press release, FDA Grants Tentative Approval for Lilly and Boehringer Ingelheim's Basaglar™ (insulin glargine injection, describes the situation: "the FDA has determined that Basaglar meets all of the regulatory requirements for approval, but it is subject to an automatic stay of up to 30 months as a result of litigation filed by Sanofi, claiming patent infringement. Under the Drug Price Competition and Patent Term Restoration Act ("Hatch Waxman"), the FDA cannot give final approval until the end of the 30-month period in mid-2016, unless the court finds in favor of Lilly earlier." Basaglar is an insulin glargine look-alike (or biosimilar), which is covered by patents under the brand name Lantus. So the lawyers are squelching Lilly's attempt to grab market share. And also squelching, maybe (we can hope, right?), some price competition between Lilly and Sanofi if they both were to sell the same insulin?

Second, there's an insulin delivery system called Oral-lyn™ that hasn't had any Phase III trials in the US. Heck, they've done practically no studies in the US, per ClinicalTrials.gov: There was one study that's now listed as "unknown" status, and a Treatment Use (compassionate use) IND that's "no longer available." Sounds like the manufacturer simply isn't interested in the U.S. market. They did submit results of a 12-week open-label Phase III study on 209 T2DM patients in India last year, as requested by the Drugs Controller General (India) (DCGI), but there's been no update on the manufacturer's website about what's cooking since then: they are delaying a conference call about the product "As Generex wishes the conference call to be as informative, comprehensive, and up-to-date as possible, management considers it appropriate to schedule the call once the DCGI's review of the dossier is complete. A further announcement with the date and other particulars of the call will be made in due course."

Why would any company go to the great lengths to develop a new insulin delivery system, but not try for approval in the United States? It's hard for me to fathom.

In May, 2005, I wrote a blog for another website (which is no longer available on line) which I titled "Oral insulin available soon - in Equador." Quoting that blog:

"Generex Biotechnology Corporation has put out a press release indicating they have obtained regulatory approval from the Ecuadorian Ministry of Public Health to sell their proprietary oral insulin spray formulation, called Oral-lyn™. So people in Equador will soon be able to spray insulin into their mouths -- with no assurance of the safety of the product because no large-scale safety studies have yet been done.

Two small studies (on 44 patients) have been published showing that it works: Oral spray insulin in treatment of type 2 diabetes: a comparison of efficacy of the oral spray insulin (Oralin) with subcutaneous (SC) insulin injection, a proof of concept study (this study had 23 patients), and Beneficial effects of addition of oral spray insulin (Oralin) on insulin secretion and metabolic control in subjects with type 2 diabetes mellitus suboptimally controlled on oral hypoglycemic agents (this study had 21 patients). Elsewhere on the internet, it is stated that the Equadorian approval was based on the results of clinical trials involving more than 250 patients with diabetes.

But the large-scale, costly Phase III clinical trials required by responsible regulators in the US, Europe, and elsewhere have not yet begun. These studies will involve well over a thousand patients, and must include a sizeable number of patients with over at least a year's exposure to the product.

Why did Generex make this announcement now, before doing any large-scale safety studies? Looks simple to me: according to Generex's CEO, "This approval will mark our transition from a development-stage company to one that will generate revenues from commercial sales." It looks like they need more money to do the big studies. Money from Equadorians [and Algerians and Lebanese] apparently.

I must respectfully disagree with the CEO's next comment, that "This approval will also enhance our ability to procure additional similar jurisdictional approvals around the world." There's simply no way that the FDA or European or other major regulatory agencies will be rushed into approval of a novel route of insulin delivery simply because people in Equador have access to it. Indeed, the other regulatory agencies will scrutinize both the unstarted Phase III safety studies they always require, and the outcomes of people using the product in markets where the product is already approved.

So, although I suppose you could book your airline ticket to Equador to get insulin oral sprays soon, I'd suggest you wait until it's been documented to be safe -- in large studies, and on the good people of Equador."

I wrote that in 2005. Since then, there are no active studies in the US, and no further publications re "oralin" in PubMed.

But one thing that Generex is willing to do in the U.S. is to sue: one financial writer panned the drug and the manufacturer at a financial website, with articles like

Generex: What Happens in India, Stays in India and Generex responded with a lawsuit for $250,000,000.00 on each of 3 counts, $50,000,000.00 on a fourth count, plus punitive damages!

Just goes to show you what can happen when corporate lawyers get into the pharmaceutical industry. If your mega-company can't make enough money developing and selling drugs, use the law to block the competition, or if you're a small company, maybe you can sue the stuffings out of a journalist.

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Disclaimer: I previously worked in pharmacovigilance (drug safety) for Sanofi (the manufacturer of Lantus) and with Pfizer, who developed another alternative form of insulin administration (Exubera).