Inside the Orphan Drug Revolution: The Promise of Patient-Centered Biotechnology

by James Geraghty

Advances in medicine have made possible better treatments for widespread, familiar human illnesses like cancer, diabetes, and heart disease. Yet there are thousands of much less common diseases, most of genetic origin, each classed as “rare” because it afflicts only a small number of people. These patient groups were long ignored by a pharmaceutical industry that judged them too small to provide a return on the investment needed to develop an effective remedy. Yet these “orphaned” diseases collectively caused misery and expense, often far greater than did more common ailments, for tens of millions of individuals and their families.

Forty years ago, a revolution that transformed the prospects of patients with rare diseases was lit by three sparks. The passage of the 1983 U.S. Orphan Drug Act resulted from public pressure brought by rare disease patients, their families, and advocates. The AIDS epidemic triggered additional activism, compounded when patients with the rare disease hemophilia became HIV-positive after infusion of tainted blood products. And the third spark was the emergence in the early 1980s of biotechnology companies like Genentech, Amgen, and Biogen employing then-new genetic engineering instead of conventional approaches to pharmaceutical development. Soon after, Genzyme became the first company to develop a treatment for a rare genetic disorder, Gaucher disease, which would come to transform the industry.

Jim Geraghty has been a passionate participant in the orphan drug revolution since its inception—a leader in the field as a strategy consultant, biotechnology executive, and venture entrepreneur. His book is in part a history, with eyewitness accounts of advances as they occurred and portraits of the pioneering scientists and physicians, tireless activists, and visionary business leaders who made the revolution happen. And it tells deeply personal stories of patients and parents willing to risk new, untried therapies. But Geraghty also uses his exceptional experience and vantage point to look forward to the immense promise of the newest technologies like gene therapy and gene editing for the treatment of patients today and tomorrow. He concludes with thoughtful consideration of important questions. Why do drugs to treat orphan diseases cost so much? How can we ensure they are affordable? How can their effectiveness be responsibly assessed? And how can access to them be expanded internationally? This book graphically and poignantly illustrates how far an important healthcare revolution has come and reminds us that if not nurtured, it could end before its immense promise has been fulfilled.

Genres: Nonfiction, Business

291 pages, Kindle Edition

Published September 16, 2022

Reviews

[Ronald J. · Rating 4 out of 5]

We will be interviewing the author on The Soul of Enterprise on November 11th. Details to follow.This book celebrates, and documents, how ordinary people were able to plug a hole in the healthcare system that the free market didn’t address—rare diseases, or what are also known as “orphan diseases.” Defined in the USA as afflicting up to 200,000 patients, and in the EU as one in 2000. They are merciless, causing far worse suffering than common diseases, and most are genetic, resulting from a defective mutation in a single gene (it can run in the family or have no prior family history). Over 6,000 distinct monogenic diseases have now been identified, ultimately topping over 10,000, afflicting an estimated 25 to 30 million Americans, and 300 to 500 million around the world. The USA passed the Orphan Drug Act in 1983, and since the FDA has approved drugs for more than 900 conditions versus fewer than 10 in the ten years prior to passage of the Act. The book celebrates the individuals and companies that made this happen, and the stories are remarkable and inspiring. With personalized medicine on the horizon, and N = 1 trials being allowed, we should see more progress in this area. The author does a wonderful job telling the stories as well as explaining the science. I enjoyed this book.

In fact, we are going to interview the author on The Soul of Enterprise on November 11, 2022. Link to follow.

[Simon Fletcher · Rating 4 out of 5]

A really interesting review of the biotechnology drug development and rare disease research. What could have been a dry read was actually well written and engaging throughout

[Jillian Shaw · Rating 5 out of 5]

I’ve been increasingly interested in how the Inflation Reduction Act has impacted incentives for drug repurposing in the rare disease space, especially small molecules, as well as how you might encourage drug repurposing for life saving treatments. This is a great history of the Kendall Square giants, especially Henri Termeer. I know the history of Vertex’s triple combination therapy for Cystic Fibrosis and Alnylam’s vision for RNAi, but it’s a great reminder of how a small, but mighty, group of scientists, entrepreneurs, and most importantly, patients, can expand access to treatment. Strong discussion addressing the hefty price tags of many of these rare disease treatments as well as ultra-rare disorders that might not have pharmaceutical interest. I was really interested to learn about the Cystic Fibrosis foundation’s royalty rights and how the foundation received a $3.3B return from a $50M seed. Food for thought for the impact of venture philanthropy. I’m looking forward to an updated version of this history that includes more women innovators in biotech.

[Mollie Plekan · Rating 5 out of 5]

I was expecting a somewhat dry review of the companies out there working in the orphan drug space but I was surprisingly wrong! Geraghty does a great job of incorporating the background of certain significant drugs, companies, individuals, and events with a captivating, storytelling-like narrative.

[Armen Shirvanian]

My interview with James Geraghty on "Inside the Orphan Drug Revolution":

http://www.armenshirvanian.com/podcas...