183 diabetes medicines   (December 14, 2009)

Earlier this year, the Pharmaceutical Research and Manufacturers of America (PhRMA) released an interesting report, Biopharmaceutical Companies Developing Record 183 Medicines to Treat Diabetes and Related Conditions. The PhRMA report states that "America's pharmaceutical research and biotechnology companies are working on 183 new medicines to treat [diabetes] and related conditions. All of the medicines in this report are either in clinical trials or awaiting approval by the U.S. Food and Drug Administration."

Some observations as I peruse the list:

The list was current as of April 27, 2009, and some of the information is already outdated: for example Byetta is now approved as monotherapy, but at the time the list was generated, the manufacturer had not yet received approval. Ditto for Onglyza (saxagliptin), which is now approved as another DPP-4 inhibitor, that competes with Januvia (sitagliptin). There inevitably are other new drugs in the pipeline that hadn't started human clinical trials last spring, that would be included if the listing were to be redone this month.

Some of the drugs that are listed were approved previously, and are seeking new indications: Avandia (rosiglitazone), which has been approved since 2000, is on the list because of the manufacturer is seeking approval to market it for prevention of T2DM. Another approved drug, Byetta (exenatide), makes the list as the manufacturer is seeking approval for use in T2DM in adolescents, and is being evaluated for once-weekly therapy and for intranasal and transdermal administration. By the time you add up everything for Byetta, there are six entries out of the 183 that are for this one drug. And the report has some listed under "B" for "Byetta," and others listed under "e" for "exenatide."

It should be pointed out that many of the drugs on the list are "me-too" or "me-three" drugs. Such drugs are in the same class as other drugs that are already approved, and may be better (or worse) than the ones that are already approved, but if they make it to market, they might make a profit for the manufacturer -- and might help hold down the prices for that class of drugs. An example: netoglitazone, now in Phase I trials, is another "glitazone," in the same class as Avandia and Actos.

Many of the drugs listed have no information about what they are or how they work: for example, ONO-5129, from a company called Ono Pharma USA is listed as a drug for T2DM that's in Phase II. Googling the drug's codename gives more information: it is a a PPAR receptor agonist ("glitazone") from a Japanese drug company, called Ono Pharmaceutical Co., Ltd. Or, in other words, it's yet another glitazone; this one from a Japanese company.

Some of the information is mildly inaccurate: for example DiaPep277 is in Phase III trials, not phase II.

Indeed, some of the "medicines" are not what are usually thought of as medications: an insulin pen, to me, is a device for delivering insulin. Stem cell therapy is on the list, as is islet cell transplantation therapy.

It's fascinating to see that there are four listings for inhaled insulin. Inhaled insulin, under the brand name Exubera, was approved by the FDA in 2006, but was a marketing disaster, and was discontinued by the manufacturer the following year. Around that time, Novo-Nordisk and Eli Lilly discontinued their inhaled insulin programs, but that hasn't stopped other companies from trying.

Inevitably, some of the drugs that are on the list will fail to be approved. At least one, remogliflozin, has been withdrawn by the manufacturer. Two, Galvus (vildagliptin) and Victoza (liraglutide) are under scrutiny by the FDA and may be approved or rejected because of adverse events that the manufacturers reported (skin lesions seen in monkeys for Galvus, and Victoza because of thyroid tumors seen in rodents). Interestingly, both drugs have been approved by European regulators, who set their own standards for what's an acceptable risk.

Speaking of Europe, the listing of 183 medications (plus-or-minus) is stated to be those in development in the United States. There are some diabetes drugs being developed in Europe, which have not yet started trials in the US. So if a global version of the listing were developed, the number would probably be quite a bit higher.

How many of the 183 will be blockbusters, game-changers, or otherwise revise the way we treat diabetes? Hard to say; I'd expect maybe a handful (or a number that could be counted on the fingers of one hand, to mix the metaphor). Some of the 183 will be approved and then fail in the marketplace (like Exubera). Some will be approved then later unexpected side effects will show up. Some will never be approved as studies show lack of efficacy or unacceptable side effects. And some will displace earlier drugs as the new drugs have better efficacy or less side effects than an earlier member of the same drug class.

But it's reassuring to see that the pharmaceutical industry sees diabetes as an area in which to focus its research. Let's hope that this focus on diabetes results in new and better ways to treat diabetes to help all of us.