Roche Wins Pertuzumab Nod in Metastatic Breast Cancer
By Jennifer Boggs
The FDA approved Perjeta (pertuzumab) in metastatic breast cancer late Friday, a move that bolsters Roche AG’s HER2 franchise with another potential blockbuster.
Pertuzumab, which began clinical development at Genentech Inc. about a decade before the South San Francisco-based biotech was snagged by Roche, was approved for use in combination with existing HER2-targeting blockbuster Herceptin (trastuzumab) and docetaxel chemotherapy in HER-positive metastatic or locally recurrent, unresectable breast cancer patients who have not received previous treatment or whose disease has relapsed after adjuvant therapy.
“Perjeta attacks HER2-positive tumors differently than Herceptin,” said Hal Barron, Genentech’s chief medical officer and head, global product development. “Based on the way the two medicines work together, the combination plus chemotherapy can prolong the time before this aggressive cancer worsens compared to Herceptin and chemotherapy alone. We are very pleased to see our efforts in studying the science of HER2 translate into another personalized medicine.”
The Swiss big pharma submitted the biologics license application earlier this year, receiving priority review designation at the FDA. And expectations ahead of Friday’s PDUFA date were high, given the impressive six-month progression-free survival (PFS) benefit reported in the Phase III CLEOPATRA study last year and the absence of an FDA advisory panel.
Designed specifically to target a different region on the HER2 receptor, pertuzumab is believed to complement, rather that compete with Herceptin, a drug that pulled in about $5.5 billion in global sales for Roche in 2011. The idea is that combining those drugs will provide a more comprehensive blockage of HER signaling pathways.
Findings from CLEOPATRA showed a 38 percent improvement in PFS when pertuzumab was added to the mix, compared to Herceptin and docetaxel alone. Overall survival data are expected in 2013. (See BioWorld Today, Dec. 9, 2011.)
Though Genentech execs said pertuzumab will be available in the U.S. within two weeks, they also revealed that they have “identified a cell growth issue” which could affect the future supply of pertuzumab. Patrick Y. Yang, head of pharma global technical operations, said, “We take this very seriously and are working with the FDA to ensure a consistent manufacturing process that maintains drug supply for the people who need it.”
Roche already submitted a marketing authorization application in Europe, which is currently under review by the European Medicines Agency.
The market for pertuzumab in metastatic disease is small – at least comparatively. Jefferies & Co. analysts have estimated peak sales of $1.9 billion. But the adjuvant setting is expected to prove much more lucrative for Roche. An approval in that indication could mean an estimated $6.6 billion more in peak annual sales.
An ongoing Phase III study, dubbed APHINITY, is testing pertuzumab as an adjuvant. It’s designed to compare rates of invasive disease-free survival in HER2-positive patients with early stage breast cancer who receive Herceptin plus an anthracycline-taxane- or taxane-platin-based chemotherapy, with or without pertuzumab.
Another ongoing Phase III trial is testing pertuzumab in combination with T-DM1 (trastuzumab emtansine), an antibody-drug conjugate that wowed attendees of the American Society of Clinical Oncology meeting earlier this month. That trial, the MARIANNE study, is investigating three treatment regimens – pertuzumab/T-DM1, T-DM1 alone or Herceptin plus chemotherapy – in first-line HER2-positive metastatic breast cancer. (See BioWorld Today, June 6, 2012.)
T-DM1, which combines Herceptin with a cell-killing agent, is partnered with ImmunoGen Inc., of Waltham, Mass. The companies anticipate filing for approval of the drug this fall for use in locally advanced or metastatic breast cancer that previously had been treated with both Herceptin and a taxane agent.
Ultimately, though, Roche has aims to combine all three breast cancer drugs – Herceptin, T-DM1 and pertuzumab – as a possible cocktail therapy in HER2-positive breast cancer. It’s part of the company’s ongoing strategy to shore up its HER2 franchise. Herceptin loses patent protection in 2014, and several companies such as Danish Synthon BV and Korean Celltrion Inc. area working on biosimilar versions that are expected to cost less.
In addition to its work with ImmunoGen, Roche has reached out to other firms working in the HER2 space. The big pharma is jointly funding a Phase II trial with Galena Biopharma Inc., which is testing Herceptin in combination with the Lake Oswego, Ore.-based biotech’s cancer vaccine NeuVax (E7 plus GM-CSF). NeuVax is designed to work by stimulating cytotoxic CD8-positive T cells to target cells expressing any level of HER2.
The study is expected to enroll 300 breast cancer patients with HER2 low-expressing tumors, with a goal of establishing the benefit of Herceptin plus NeuVax vs. Herceptin alone in an adjuvant setting.
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