Quite a few biotech entrepreneurs go to work each day operating under the assumption that clinical trial data is king. If you put together a rock-solid dataset from a big clinical trial that says your experimental drug beats today’s standard of care, then you’re onto something big, or so the line of thinking goes.
Everything should fall into place. Patients will demand the drug. Doctors will prescribe it. Your stock will soar. You’ll make a fortune.
Wrong. Sometimes great drugs reach the market, and flop. That sad story played out over the past decade with a drug from GlaxoSmithKline for non-Hodgkin’s lymphoma. It could have helped tens of thousands of patients, but never came close to fulfilling its potential.
The drug was tositumomab combined with iodine 131 (Bexxar). GlaxoSmithKline said recently that it will quit making and selling the drug in February 2014, a little more than a decade after it was approved by the FDA. Usage peaked in 2006, but sales have been dropping 30 percent annually since then. Fewer than 75 patients in the U.S. got the drug last year, a Glaxo spokeswoman recently told Oncology Times.
“It’s a shame to see this being pulled off the market,” said Anas Younes, the chair of the lymphoma service at Memorial Sloan-Kettering Cancer Center in New York, when we spoke by phone last week. “If you look at this drug, it has about a 70 percent response rate, in one shot. You don’t have to keep giving it for 2-3 years. It’s simple, with not much toxicity. Many patients could have benefitted.”
There are many reasons why Bexxar failed, which I’ll get to in a minute. But the story starts, like so many in biotech, with a tantalizing scientific concept.
The idea, driven by Mark Kaminski, Richard Wahl and colleagues at the University of Michigan in the 1980s, was simple. It was to take a genetically engineered antibody, aim it at a specific marker found in abundance on cancer cells, and tack on a dose of radiation to give it extra tumor-killing punch. This was the kind of product that molecular biologists had dreamed of since the late ‘70s, when there was talk of “magic bullets” or “targeted missiles” against cancer. Bexxar and its competitor—ibritumomab loaded with a radioactive isotope called yttrium-90 (Zevalin)—arrived on the U.S. market in the early 2000s as the pioneers of this new class of treatment known as “radioimmunotherapies.”
Bexxar, developed in the late ‘90s by South San Francisco-based Coulter Pharmaceutical and acquired in 2000 by Seattle-based Corixa, had a lot going for it. The drug was aimed at a protein marker called CD20, which was already a validated molecular target for cancer, based on the success a couple years earlier of a so-called “naked” antibody from Genentech and Idec Pharmaceuticals, rituximab (Rituxan). Corixa had a well-respected CEO in Steve Gillis who attracted scientific talent, and raised lots of cash. It had a Big Pharma partner in Glaxo to help it manufacture and market the drug to the fullest.
Most importantly, Bexxar had clinical trial data on its side. The pivotal study of Bexxar was small, but offered strong evidence. It enrolled 40 patients with non-Hodgkin’s lymphoma who had no other options left at the time, because their disease had worsened after they got rituximab and several rounds of chemotherapy. The trial showed that 63 percent of those very ill patients had significant tumor shrinkage on Bexxar, and the benefit lasted a median time of more than two years (25 months). About 29 percent of patients went into complete remissions, and researchers weren’t sure exactly how long they’d last because so many remissions were still ongoing at the time of FDA approval. Several patients from the earliest clinical trials in the early ‘90s were still alive more than a decade later, and became forceful advocates for the drug.
Like all cancer drugs, Bexxar came with some baggage—significant depletion of infection-fighting white blood cells, oxygen-carrying red blood cells, and clot-forming platelet cells. But those tended to be manageable side effects. There were warnings that the drug might cause nasty immune reactions sometimes associated with antibody infusions, but that’s also true for rituximab. It wasn’t a show-stopper for Bexxar.
Still, the drug was held up by a series of FDA questions and requests for information. The new drug application was first filed in June 1999, and wasn’t approved by the FDA until four years later. That delay, an excruciating time for Corixa, allowed a combo of Rituxan and chemotherapy more time to cement its position as the standard of care in non-Hodgkin’s lymphoma.
Despite the delays, it looked like
