Celgene Corp.’s nanoparticle formulation of paclitaxel Abraxane is now FDA-approved for first-line treatment of non-small cell lung cancer. While investors’ expectations are low due to lackluster survival data in NSCLC, there may be more opportunity in other new indications.

Abraxane (albumin-bound paclitaxel) for injectable suspension was approved as a first-line treatment for locally advanced or metastatic NSCLS, FDA announced Oct. 12. The drug was previously approved in 2005 for patients with metastatic breast cancer who did not respond to combination chemotherapy or who relapsed within six months of adjuvant chemotherapy, meaning treatment given with surgery to prevent recurrence.

Approval of the new NSCLC indication was supported by the Phase III, open-label CA-0131 study of over 1,000 patients, which tested Abraxane weekly with carboplatin every three weeks against paclitaxel every three weeks with carboplatin. In the study, Abraxane met the primary endpoint for improving overall response (33% for the test drug arm compared to 25% for the comparator). Overall response rate differences were more striking in squamous cell carcinoma, at 41% for the Abraxane patients compared to 24%, and also in large cell carcinoma, 33% compared to 15%.

When Celgene picked the drug up through its $2.9 billion cash and stock acquisition of Abraxis BioScience Inc. in July 2010, the hope was that product sales would grow along with approvals for new indications Also see "Celgene Moves Into Solid Tumors With $2.9 Billion Abraxis Acquisition" - Pink Sheet, 5 July, 2010.. Abraxane had about $314 million in sales in 2009 and $386 million in 2011.

However, following the Abraxis acquisition, the company reported that the Phase III NSCLC trial had failed to show a statistically significant PFS benefit.

“We believe the lack of any PFS benefit in either squamous or non-squamous patients is likely to provide a limited commercial opportunity,” Cowen and Company analysts noted in their March 2012 Therapeutic Categories Outlook report.

In an Oct. 12 note, UBS Investment analyst Matthew Roden said that the NSCLC approval is in line with expectations because the endpoint was met in the study, which was designed with a special protocol assessment. However, he also concluded that the label doesn’t allow Celgene to make a PFS or OS claim, which may limit overall uptake in this disease.

Median PFS was 5.6 months for Abraxane vs. 5.7 months for the comparator, not a statistically significant result, while overall survival was “slightly better” at 10.7 months compared to 9.5 months, the company reported at the American Society of Clinical Oncology meeting on June 2. In this analysis, Celgene also noted a trend toward better PFS in elderly patients, at 8 months compared to 6.8 months.

On the bright side, Roden noted that “FDA is willing to expand the Abraxane label with modest signals of efficacy to a comparator, which in our view is a positive leading indicator for opportunities in melanoma and pancreatic cancers.”

On Oct. 2, Celgene announced that Abraxane met the PFS primary endpoint in the Phase III CA033 study in chemotherapy-naïve melanoma patients. Full results will be presented at the Society for Melanoma Research meeting in Los Angeles in November.

Abraxane is also in Phase III for pancreatic cancer.

Abraxane Lung Cancer Approval Comes With Questionable Commercial Value

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