CLEVELAND, Ohio — Dr. Roger Macklis’ radioactive mission could reach its half life later this year.
The Cleveland Clinic oncologist has long sought an expanded role for radioimmunotherapy — the directed delivery of radioisotopes into the body to target and kill tumor cells. For months now he’s championed that cause through the owners of the underachieving treatment Zevalin.
Their strategy: Doctors will warm to radioimmunotherapy if enabled to piggyback Zevalin on chemotherapy they’re already giving cancer patients to increase the effectiveness of initial lymphoma treatments.
The U.S. Food and Drug Administration will decide in July whether to allow Zevalinto expand its label to promote such use. This expansion could broaden its application beyond that of a second-line treatment, potentially adding 20,000 patients nationwide and fulfilling Macklis’ personal goal for a greater use of the treatment.
“For me, this is a case in which everything is lined up for me,” Macklis said. “It’s the right thing to do. It’s a disruptive technology. And I think the medical data is in support of this.”
Disruptive. To understand Macklis’ feelings about this opportunity is to understand that word.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Disruptive technology is the promise of something that is new, cheaper and — eventually — better. It’s the Internet. The musket. Plastics. It’s Clayton Christensen, the Harvard Business School professor who wrote the book (several of them, in fact) on disruptive technologies and innovations — and a man who Macklis said he once approached about the disruptive potential of radioimmunotherapy.
“This,” Macklis said of radioimmunotherapy, “is a classic disruptive technology.”
Radioimmunotherapies like Bexxar and Zevalin are only for non-Hodgkin’s lymphomas that have relapsed or not responded to other treatments. Macklis’ enthusiasm crystallized through the case of Betsy de Parry, a Michigan woman who in late 2002 used radioimmunotherapy after chemotherapy failed, fully recovered, and is alive today.
Macklis’ embrace of drugs like Zevalin and Bexxar are also based on his profession. He chaired the Clinic’s Department of Radiation Oncology for 12 years and still works in the department. He’s also served on the National Academ of Sciences’ Special Task Force on Radiopharmaceutical Sciences and Nuclear Medicine. (He has received no money or other reimbursement for his support of Zevalin.)
“I think he has a lot of intensity,” said Dr. Steven M. Larson, chief of nuclear medicine at Memorial Sloan Kettering Cancer Center in New York and the co-director of its Ludwig Center for Cancer Immunotherapy.
“I remember a guy who is very smart, intelligent and passionate about what he believes in. I think he’s willing to go to battle for his ideas, and I think that is the key to his success,” Larson said about Macklis.
But de Parry’s case was the anecdotal evidence to complement what Macklis thinks is clear research that shows radioimmunotherapy’s therapeutic advances.
Yet immunotherapy drugs have floundered. Zevalin was predicted to sell up to $200 million annually when it started almost eight years ago. But it hasn’t sold more than $20 million in the past several years, and sales last year declined to $11 million, according to its parent companies’ financial statements.
As a result, Zevalin has bounced from company to company. In February, Washington’s Cell Therapeutics Inc. sold its remaining stake in the drug to business partner Spectrum Pharmaceuticals.
“I don’t believe that this drug can substantially increase sales,” Morgan Joseph & Co. analyst Shiv Kapoor told Reuters after the Spectrum purchase.
Some blame the companies for not marketing their drugs effectively. Oncologists say that there is not enough evidence proving the effectiveness of radioimmunotherapy.
Some radioimmunologists and executives at Cell Therapeutics say oncologists are discouraged from using the drugs through a mix of poor insurance reimbursement, regulatory red-tape and training requirements. The label expansion sought for Zevalin would enable it to be used like similar therapies already are in Europe.
“Although Dr. Macklis and we believe that Zevlin has a major role, doctors had other options,” said Jack Singer, Cell Therapeutics chief medical officer. “This is certainly more difficult than [drugs] they can give in their office.”
So Macklis’ approach has been to campaign — online, with drug companies and with his peers — for a broader use of Zevalin with chemotherapy. He worked with Cell Therapeutics and urged the company to push for the label expansion, which was applied for in January.
Macklis has waged his own online campaign via Within3, a professional network for physicians, for which he works as an adviser and in which he owns an equity stake. Macklis built an online community there to promote the front-line approach to radioimmunotherapy with like-minded physicians.
He hopes to present research this fall at the American Society for Therapeutic Radiology and Oncology (ASTRO) that shows more success of radioimmunotherapy.
Radiation oncologists are a fragmented bunch, but Macklis’ approach has been part of a broader movement to unify them, said Larson of Sloan Kettering. Larson also said Macklis’ efforts could help bring about greater collaboration among oncologists.
But is Macklis — or radioimmunotherapy — truly disruptive? If the FDA’s approval were to move ahead, the procedure would likely be more costly than current therapies, not less, he admits. In time, he says, as more physicians use the approach, the costs could drop.
That’s why Macklis’ ASTRO presentation may be particularly important. He thinks there is enough evidence to show that mixing radioimmunologics with chemotherapies can extend the time between cancer recurrences – known as “remissions” – by up to two years.
But he thinks broader use of the radioimmunotherapy drugs is hindered by insufficient data for long periods of time that indicate dramatic improvements in results.
“It’s going to take awhile longer to show survival differences [that could] change many of the opinions that are on the fence,” he admits.
[Front-page photo courtesy of Flickr user wired.lain]
