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Perjeta Nod Boosts HER2 Portfolio in Breast Cancer

By Jennifer Boggs
Managing Editor

Genentech Inc. said it will be able to meet demand for newly approved Perjeta (pertuzumab), which it plans to roll out within the next two weeks, though the San Francisco-based biotech acknowledged it will have to resolve a manufacturing issue that could affect future supplies of the HER2-positive breast cancer drug.

"We do expect to meet demand," assured Susan Wilson, manager of corporate relations for Genentech. She explained that recently a "Perjeta-specific cell growth issue" was identified that might affect future supply, adding that the firm already is working on a manufacturing campaign to address the issue and "ensure that we will be able to provide the drug to every patient who needs it."

Perjeta, which began clinical development at Genentech about a decade before the biotech was snagged by Roche AG, was approved Friday night after a priority FDA review 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.

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.

"Perjeta attacks HER2-positive tumors differently than Herceptin," said Hal Barron, Genentech's chief medical officer and head of 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."

Swiss-based Roche submitted the biologics license application earlier this year 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.

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.)

Genentech has priced Perjeta at $5,900 per month. Monthly Herceptin therapy costs $4,500 per month.

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.

Genentech hasn't given a date for when APHINITY data are expected. "It will depend on a few different factors," Wilson told BioWorld Today.

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 last week. 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, and data from that trial are expected in 2013. (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.

"We started researching the role of HER2 in cancer 30 years ago," Wilson said. That work led to the 1998 approval of Herceptin, "and Perjeta and T-DM1 are coming out of the same lab, with many of the same researchers."

Roche even has aims to combine all three breast cancer drugs – Herceptin, T-DM1 and pertuzumab – as a possible cocktail therapy in HER2-positive breast cancer. "Our ultimate goal is to determine a combination or regimen that will provide the maximum benefit to patients," Wilson said.

Perjecta – and T-DM1 if it's approved – also adds another potential blockbuster to shore up Genentech's HER2 franchise. Herceptin loses patent protection in 2014, and several companies such as Danish Synthon BV and Korean Celltrion Inc. are working on biosimilar versions that are expected to cost less.

In addition to its work with ImmunoGen, Genentech and parent Roche have reached out to other firms working in the HER2 space. For instance, Roche 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.