Dr. Ed Ratner is a physician, former entrepreneur, and CLL patient who wrote a review from his unique perspective on this book that chronicles the development of two blockbuster drugs that have revolutionized the care of CLL / SLL and made fortunes for early investors.
Dr. Ratner comments on the thorny questions raised by the book around drug costs and the often underappreciated role of patients or physician researchers in drug development.
The book is available on Amazon, Audible, and several other sites.
Please enjoy Dr. Ratner’s review, below.
When I was diagnosed with CLL in January 2015, the first effective oral treatment, ibrutinib (Imbruvica), was barely on the market, only one year after its limited approval by the Food and Drug Administration (FDA). At that time, I was trying to understand the disease and if and when I would require treatment. Initially, ibrutinib was approved only for treatment after other options failed. So, this drug wasn’t remotely on my mind as I searched the medical literature about CLL over the following months.
By November 2022, I had increasing symptoms due to CLL. By then, ibrutinib and a related Bruton-Kinase (BTK) inhibitor, acalabrutinib (Calquence), had become common initial treatments for this disease. Only a few months later, the story behind these two drugs, from their discovery to the immense profit-taking by early investors, was described in For Blood and Money, Billionaires, Biotech, and the Quest for a Blockbuster Drug, by Nathan Vardi.
As a CLL patient, a physician, and a former (minimally successful) entrepreneur, I found this book fascinating. Although the author, a business writer, focuses on the people who worked for and invested in the drug companies, I identified with the doctors who prescribed these novel drugs in research studies and the patients who accepted the challenges and risks of participating in that research. Together, I see it as they provided me with good options when my need arose.
The story of drug development and its costs plays out with politicians and the public decrying the rapidly growing costs of medical care (much of which is due to drug expense) and the pharmaceutical industry responding that any control of drug costs will stifle innovation to save lives. This book provides in-depth reporting on these issues through a sports reporter-like perspective on the game of drug development. With my inside perspective on CLL and medical care, I knew the outcome (success of the drugs) but was intrigued by the detailed recap.
The molecule which became ibrutinib was not originally intended to be a drug. The chemical formula was sold by the company that discovered it to a desperate start-up drug company, Pharmacyclics. It was priced at almost nothing in a package with several more promising compounds. It was 2008, and a key investor in Pharmacyclics, who had no scientific background or experience in the biomedical business, became its CEO.
This book chronicles the other savvy investors in that company and the turnover of key scientists and business leaders at Pharmacyclics over the years. Those who left that company joined another drug start-up, Acerta, which developed acalibrutinib. That more targeted drug has now substantially supplanted ibrutinib as the leader in new prescriptions for a BTK inhibitor. [A third drug in this class, zanibrutinib, was also recently approved for CLL.]
Other published reviews of For Blood and Money cover the sometimes heroic, sometimes tragic stories of the drug companies and their employees. Instead, I would like to highlight some of the anecdotes about the academic hematologists and their patients who had less pecuniary rewards from the development of these drugs.
A company with a new drug doesn’t directly find patients to test it. It typically partners with university medical centers and their doctors to find appropriate patients willing to be experimental subjects. For the universities, the payments far exceed the costs of paying its staff to do the necessary work and the modest payments to enrolled patients. For the doctors, these partnerships are supplements or alternatives to competitive grants to support the teams required to do medical research. The leaders of drug testing projects may become the key authors on papers published in major journals and invited speakers at conferences, the markers of success in academics. Consulting contracts with a drug company for advice and speaking engagements can significantly increase professors’ income beyond what universities are allowed to pay faculty members. The public recognition and access to novel therapies then allow the medical practice at the university to attract more patients and other grants and contracts. The book briefly but inadequately describes the key roles of some leaders in CLL drug trials, such as Dr. Byrd at The Ohio State University and Susan O’Brien at MD Anderson Cancer Center. However, the author highlights their extraordinary scientific rigor and advocacy for their patients.
The other group that is only cursorily described in this book is the patients enrolled in the research trials. It is their courage and/or desperation that leads them to make the sacrifices necessary to advance our knowledge by taking unproven drugs. Two stories about CLL Society leaders were described. Dr. Brian Koffman, who later became the founder of CLL Society, took time away from his medical practice and moved from California to Ohio for several months to participate. When returning home, he considered the ibrutinib so valuable he kept it in his pocket rather than his carry-on bag in case of emergency evacuation of the plane. Another CLL Society leader, Terry Evans, enrolled in a trial that compared ibrutinib to another drug (not as likely to be effective for him). He was randomized to the other drug, but when that failed, advocacy efforts by him and doctors allowed him to get ibrutinib, which worked well for many years. A third story recounts an unnamed patient near death from CLL in 2014, who became the first person to try what became known as acalabrutinib. She went on to dramatically improve with lymph nodes shrinking and no longer needing transfusions. Their persistence represents a great story by itself.
Before having CLL, I thought of medical discovery as something that helped my patients and sometimes family members. This book left me gratified by the description of so much effort made by so many to potentially prolong my life. At the same time, I am conflicted about the public policies related to those efforts. Can and should the relatively unfettered capitalism determine how to invest in medical advances? For people like me with CLL, the extraordinarily high price permitted for a drug such as ibrutinib (U.S. retail at over $13,000 per month, likely for many years) encourages investors and, thus, research. For example, Vardi states that when ibrutinib was sold to the drug company AbbVie, the $3.5 billion payday personally to the CEO of Pharmacyclics was “one of the greatest Wall Street trades ever – in any industry.” For a variety of reasons, even as newer drugs and drug combinations come on the market, prices don’t drop. At the same time, there is inadequate investment in new drugs that are only required short term, such as antibiotics for infections that are resistant to current medications.
Another concern this book only hints at is the paucity of emotional and financial support for patients enrolling in research trials and those not eligible. To avoid coercion, payments to research subjects are limited, while their contributions to the financial success of investors can be enormous. Should the existence and success of organizations such as the CLL Society and other disease support organizations be so dependent on the drug companies that contribute a tiny fraction of their profits to provide education and support groups to those who will pay for the drugs through premiums and co-pays? For the majority of those with CLL on Medicare, the out-of-pocket costs per year now exceed $10,000 for those on treatment for CLL. Is that necessary to support new drug development investments?
This book was published too late to influence my treatment decision. Yet, it greatly helped me understand how and why I had options. As a highly engaging history of a type of business that affects almost everyone, I would encourage its reading by people connected to CLL, health care professionals, and trainees, investors interested in biomedical opportunities, and everyone who takes prescription medications.
Edward Ratner, MD
Minneapolis VA Geriatrics Education Evaluation Clinical Center
Associate Professor of Medicine
University of Minnesota