(++++) RARE AND NOT SO RARE

Inside the Orphan Drug Revolution: The Promise of Patient-Centered Biotechnology. By James A. Geraghty. Cold Spring Harbor Laboratory Press. $29.

     Whether rare and well-known or rare and little-known, diseases affecting a relatively small number of people are a big business collectively. But they are a very small business individually, not worthwhile for major pharmaceutical companies to spend years of time and hundreds of millions of dollars developing treatments for them – especially not in light of the ongoing, virtually never-ending push by politicians to bring drug prices down. After all, if even medicines that treat large numbers of people have to be sold at lower and lower prices, all the while facing the “patent cliff” after which their protected status (which in the U.S. lasts 20 years from the date of first patent application, a date not necessarily related to actual sale or availability of a drug) disappears and therapeutically identical generics take over, then why should pharmaceutical firms make a major effort to create medicines that, by definition, can help only a relatively small number of people? A good question – answered in part by devising the term “orphan drugs” to refer to medicines that treat “orphan diseases,” which affect too few people to attract big money from big pharma.

     Then, enter small biotech companies, regarding which James A. Geraghty has more than a little knowledge, having chaired five public ones and been involved in the orphan-drug field for four decades. Inside the Orphan Drug Revolution is part history, part advocacy, part (happily, not too large a part) self-aggrandizement – a book that does not merely recite heart-wrenching stories of people suffering from rare diseases (although it contains those), does not merely get into the politics of drug research and approval (although it contains that, too), but makes a genuine effort to argue for the importance of continuing research into treatments for conditions that collectively affect many people and many families even though they individually affect relatively few.

     How many is “few”? Ah, the devil in the details: things get complicated quickly. Officially – under the definition of the Orphan Drug Act of 1983 – an orphan disease affects fewer than 200,000 people in the United States (other nations have other definitions, but Geraghty’s book is primarily U.S.-focused). As it happens, though, some orphan diseases are quite well-known, such as hemophilia and sickle cell anemia (also called sickle cell disease). And the federal government, which propagates the “orphan disease” definition in the first place, sometimes sends confusing messages about better-known rare diseases, as in the Center for Disease Control and Prevention’s definition, “Sickle cell disease (SCD) is a common inherited blood disorder in the United States, affecting an estimated 70,000 to 100,000 Americans.” So although it is a rare disease in the population as a whole, it is a common one among inherited blood diseases.

     Confused messaging is only one element making the battle against orphan diseases difficult. The 1983 Orphan Drug Act, the banner achievement in the field, very nearly did not come into existence – until a well-placed advertisement caught the right person’s eye: “President Reagan planned to veto the Orphan Drug Act but changed his mind after supporters took out a stark ad in a paper read by his wife Nancy while they were on a Christmas vacation in Palm Springs.” With such small and surprising steps, neatly worked into the narrative of Inside the Orphan Drug Revolution, do science and medicine advance. Make that “science, medicine, and entrepreneurship,” which Geraghty cites as the three roots of his book’s titular revolution. Indeed, Geraghty – unsurprisingly, given his non-medical, non-scientific background (he has psychology and law degrees) – ranks the three elements essentially equally: “The root that stimulated the linkage of biotechnology and genetics came from the entrepreneurs” (hence the element of self-praise in the book).

     It is worth mentioning some of Geraghty’s sobering statistics regarding orphan diseases to understand why the field, and Geraghty’s own place in it, are worth readers’ time even if they do not personally suffer from a rare disease: there are an estimated 7,000 rare genetic diseases in all, most affecting only tens to hundreds of people – but the group as a whole has an impact on nearly one-tenth of the U.S. population. Of course, as with all statistics, one’s reaction to the numbers is dictated by how they are emphasized: lots of people are affected by these diseases, but very very few are affected by most of them (which explains why about 95% have no available treatment). The issue for major pharmaceutical companies is the very very few emphasis; for individual families that are affected, and for advocates such as Geraghty, the lots is what matters.

     So in addition to explaining orphan diseases and orphan drugs, and detailing entrepreneurial and political issues associated with the field, Geraghty eventually becomes prescriptive regarding the sustainability of the “revolution” of his book’s title. This, unsurprisingly, is where things get sticky. He argues that in the future, the revolution “must be led by patients,” and he talks about focusing on “ultra-orphan diseases” that affect fewer than 10,000 people in the U.S. He argues for much-more-common screening for orphan and ultra-orphan diseases, even when no treatment is available, since screening itself has become far easier and more technologically advanced in recent years – and he then broadens his scope with some rather Utopian ideals, such as ensuring that all (not “nearly all”) people who need orphan drugs receive them, both in richer nations and in poorer ones. He even pulls in, unnecessarily, some of the cause-of-the-day language regarding “increasing organizational diversity…among historically underrepresented U.S. minority groups.” But he goes beyond pie-in-the-sky thinking when he gets down to some of the basics of drug development and pricing, for instance by suggesting that politicians focus on reducing co-pays for drugs rather than the drugs’ prices – since the out-of-pocket co-pay is what will most likely limit a patient’s access to needed medicine. It is true that Inside the Orphan Drug Revolution is, on one level, just another book about how scarce societal resources should be redirected toward something the author cares about. On another level, though, the book is significant because it does such a good job of indicating why readers themselves, even those not personally affected by orphan diseases, should pay more attention to the topic.