Pfizer Inc., Eli Lilly and Co. and Novartis AG have dug an idea out of the pharmaceutical dustbin to create new medicines that are showing blockbuster potential against hard-to-treat forms of breast cancer.
In findings reported Sunday, Pfizer’s drug, called palbociclib, stopped tumor growth for 20.2 months in advanced forms of hormone-related breast cancer, twice the time seen with an older therapy alone. The treatment, projected to add $3.1 billion in sales by 2020, is based on a strategy largely abandoned in the 1990s after it failed to show consistent response against a broad range of cancers.
Since then, a deeper understanding of cancer’s diverse genetic underpinnings has emerged, giving drugmakers new information on how the drugs, called CDK inhibitors, keep tumors from growing and spreading. The breakthrough offers the first major new therapy in a decade for patients whose breast cancer fails to respond to other treatments, doctors say.
“There haven’t been a lot of new drugs in this space,” said Judy Garber, an oncologist at the Dana-Farber Cancer Institute in Boston. “These, to me, are the most exciting drugs to come along in the treatment of estrogen-receptor positive breast cancer in a long time.”
The Pfizer findings, coming in the second of three phases of testing normally needed for U.S. approval, were reported at the American Association for Cancer Research meeting in San Diego, along with results from an earlier-stage study on a similar treatment from Indianapolis-based Lilly.
The Pfizer outcome may help the company secure faster clearance for a therapy that could one day generate peak sales of $6 billion a year, said Mark Schoenebaum, an ISI Group analyst in New York.
Pfizer said it is talking with the Food and Drug Administration about such a possibility. “We’re just not far enough along with the FDA yet” to announce such a move, said Gary Nicholson, head of Pfizer’s oncology business, in a conference call with analysts.
While Pfizer’s palbociclib improved progression-free survival time compared with existing therapy, it wasn’t as strong a finding as investors expected, ISI’s Schoenebaum said in a note to clients. That may cause the New York-based company’s stock to drop, he said.
Pfizer isn’t alone in pursuing CDK drugs, which block a genetic pathway for cellular growth. Lilly, London-based AstraZeneca Plc and Novartis, based in Basel, Switzerland, are all testing targets among about 20 types of CDK blockers, with the breast tumor drugs the furthest along.
Lilly’s drug, called bemaciclib, stopped tumor growth for an average of 9.1 months, according to results announced at the cancer meeting yesterday. About 25 percent of patients with hormone receptor-positive breast cancer saw their tumors shrink while 55 percent had them stay the same size.
It’s too early to know exactly how the Pfizer and Lilly drugs compare, ISI’s Schoenebaum said. One difference is that Lilly’s therapy can be given continuously, he said, while patients using the Pfizer product may need to break from treatment every three weeks.
“There is very little, if anything, in Lilly consensus estimates for this drug — so, in theory at least, it represents all upside,” he said.
Breast cancer is the most diagnosed cancer among American women with 207,000 cases in 2010, according to the U.S. Centers for Disease Control and Prevention. Hormone-sensitive cancers are the most common type in post-menopausal women with metastatic or advanced disease, and is among the deadliest.
The CDK strategy almost didn’t make it. In the early 1990s, researchers suspected CDK inhibitors could be used to slow uncontrolled growth in a broad spectrum of cancers. The science at the time, though, was unable to identify subtle differences in how the inhibitors worked in different types of tissue, and the research was largely scuttled after trials shows a lack of consistency in outcomes.
“The Wright brothers probably had some prototypes that didn’t work,” said Mace Rothenberg, a senior vice president at Pfizer’s oncology unit, in comparing development of the new drugs to the early days of airplanes. “They had to get all the right pieces in place, and they had to have the right conditions for it to fly.”
Without being able to identify exactly which cell functions were affected by the CDK inhibitors, researchers back then were basically taking shots in the dark, said Clive Stanway, chief scientific officer at Cancer Research Technology, the drug licensing and commercialization arm of Cancer Research U.K.
“We didn’t know which disease setting to put a particular CDK inhibitor into,” Stanway said. As a result, CDK blockers became “a backwater” for researchers.
Since then, scientists have learned more about how genetics affect cancer. Instead of it being one disease, researchers now believe it is dozens of diseases, each with their own unique genetic characteristics. In determining that, they have looked deeper into the genetic switches that turn malignancies on and off, giving them new insight in how the CDK inhibitors block growth in different cell types.
The drugs from Pfizer and Lilly are being tested in patients whose disease has spread from their breasts into their brain, lungs and elsewhere. Both are moving their therapies into final-stage testing. Novartis’s similar drug also is in a late- stage trial with an expected filing for marketing clearance in 2016.
“It’s the early days but there’s a lot of excitement and a lot of potential,” said Richard Gaynor, vice president of product development and medical affairs for Lilly’s oncology unit. “It’s certainly an area that has caught our attention and the attention of other groups in the field, and we’ll see how it plays out.”