It's heralded as the "diabetes cure around the corner". But will pancreatic islet transplantation trigger the demise of the insulin market? Brian Morrissey, consultant with The Frankel Group, argues that novel insulin delivery will keep sales as energetic as ever.
The insulin pen was hailed as a major revolution in diabetes treatment. Now twenty years on, another revolution has begun. Latest research promises yet more groundbreaking advances in therapy and a big shakeup of the diabetes market.
While several of the big pharmaceutical companies strive to develop various forms of non-injected insulin, recent excitement has focused on a potential "cure" for the disease. The New England Journal of Medicine's July 27, 2000 issue announced a new technique that freed type 1 diabetes mellitus patients from insulin injections. Researchers from the University of Alberta took functional islets from donor pancreases and transplanted them into the liver of patients. With immunosuppression the donor cells were not rejected and continued to produce insulin. Dr James Shapiro, who led the study, confirmed that all seven patients showed excellent control of blood sugar levels and quickly attained insulin independence.
Islet transplants are not a new idea, but previous studies indicated that no more than eight percent of patients who underwent experimental transplants remained independent of insulin therapy after one year. However, the so-called Edmonton protocol looks revolutionary and should be taken seriously. Already larger scale experiments are underway to speed its development. In particular, the National Institutes of Health is spending $5m to globally expand studies and investigate the underlying immune mechanisms involved.
End of insulin - as we know it
No-one can scoff at the potential for such transplants to transform patients' lives - and the diabetes market. But is the $3bn global insulin market under threat? Should Eli Lilly and Novo Nordisk, the world's largest insulin producers, begin to worry?
The hype that surrounded the Dr Shapiro's paper tended to ignore the central tenet of transplantation: long term immunosuppressive therapy. The risks of such chronic measures, which debilitate the body's immune system to prevent the rejection of transplanted tissues, stand to outweigh the benefits of transplantation for many diabetics. Furthermore, the cost of such therapy typically exceeds $10,000 per year. Transplantation is by no means a cheap option - and not particularly pleasant for the patient either.
The NEJM also tried to temper enthusiasm in an editorial that accompanied the report. It noted that donations of pancreases after death were hardly commonplace. "It is no fantasy that this is a giant stride," the article concluded. "If success continues over the next few years, it is the supply-and-demand issue that will determine whether islet transplantation will become a readily accessible therapeutic option for patients with diabetes."
Furthermore, islet transplantation is only appropriate for type 1 diabetics. Most diabetics do not suffer from an inability to produce insulin (type 1 or insulin dependent diabetes), but from a condition of insulin resistance (type 2, non-insulin dependent diabetes). Patients with the latter condition produce insulin, but the body is unable to use it to reduce blood sugar levels. Type 2 patients account for about 90% of the 14 million diabetics in the US. These patients eventually progress to insulin injections as resistance becomes greater, and account for about 75% of the insulin-using population, and as much as half of the total insulin usage in the US.
Insulin on the up
It looks as if the leading pharmaceutical companies can rest assured that the demand for insulin will continue into the foreseeable future. In fact, the market may grow substantially. Suggestions that transplantation procedures will replace insulin therapy for all diabetics are greatly exaggerated.
With the majority of patients still requiring regular insulin doses, there's everything to fight for. A quartet of pharmaceutical giants - Pfizer, Novo Nordisk, Eli Lilly, and Aventis - continue to invest considerable funds in developing the next generation of insulin products. This is their bid to capture market share in a largely undifferentiated field.
All four have collaborated with delivery specialists such as Inhale Therapeutic Systems (Pfizer and Aventis), Aradigm (Novo Nordisk), Dura Pharmaceuticals (Eli Lilly) in the pursuit of the insulin "Holy Grail," a method of delivery that replaces the burdensome, and sometimes painful, self-injection method.
The primary focus has been on delivering insulin via the lung, although Eli Lilly recently signed a deal with Generex to develop a form absorbed through the cheek. The advances made by these companies hold the promise of improving the lives of millions of diabetics in the very near future. In fact, thousands of patients currently enrolled in clinical trials may already be seeing those benefits. According to analysts at SG Cowen, patients in Inhale and Pfizer's smaller Phase IIb trials were able to tighten control over glucose levels, and 80 percent of type 1 patients and 92 percent of type 2 are continuing with pulmonary treatment in study extensions.
For the successful developers of pulmonary or buccal insulin, the payoff will be substantial. Volume stands to grow as insulin loses its needle stigma with patients. Also, safety-conscious physicians may increase usage of insulin, since without the need to fight patients with "needle-phobia," inhaled insulin may represent a more attractive alternative to oral therapies with troublesome side effect profiles.
Along with the superior efficacy will come price increases. Delivery through the lung is not as efficient as an injection, and therefore requires five to 10 times the amount of insulin, depending on the device. However, now that insulin is a commodity product, the extra hormone required per delivery will not in itself justify the expected hike in prices. Rather, the premium price tag on inhaled insulins will position them in direct competition with oral medications, already at a significant premium to that of injected insulin.
Pfizer and Inhale recently forecast sales of their pulmonary insulin product at $2bn in the first year after its launch, expected by the end of 2002. The Aradigm/Novo Nordisk product is not far behind. For the entire diabetes community, which hopes that a cure lies somewhere in the not-so-distant future, the burden of insulin injections could be relieved within three years. For the pharmaceutical companies the insulin market is very much alive and well.
Source: The Frankel Group (www.frankel-group.com)