Investors will have to wait for November for details, but Celgene Corp. said Abraxane met its primary endpoint of progression-free survival (PFS) in a Phase III metastatic melanoma trial by the company's Swiss subsidiary.

Celgene's stock (NASDAQ:CELG) reacted slightly, closing Tuesday at 78.44, up $1.66, on word that the nanoparticle albumin-bound version of paclitaxel, already approved for breast cancer, showed efficacy against the most deadly skin tumor.

Savade Solanki, analyst with Decision Resources, called the news "very promising," adding that the PFS advantage "could well translate into an overall survival benefit upon maturity of the study."

The trial, called CA033, enrolled 529 chemotherapy-naïve subjects, and compared results of patients given Abraxane to those with patients dosed with dacarbazine, the only chemo agent approved by the FDA for metastatic melanoma.

Summit, N.J.-based Celgene's subsidiary, Celgene International Sàrl, of Boudry, Switzerland, randomized the patients to get either Abraxane at a dose of 150 mg/m2 weekly for three out of four weeks, or 1,000 mg/m2 of dacarbazine every three weeks. Secondary endpoints included overall survival (OS), overall response rate and disease control, safety and tolerability.

The safety profile in the CA033 trial worked out similarly to those in other pivotal trials with Abraxane, Celgene reported, but more details will not be disclosed until the Society for Melanoma Research Congress 2012 in Los Angeles, which takes place the second week of November.

Meanwhile, the trial has not tallied enough events to calculate OS, which will likely need to beat dacarbazine, wrote Michael Yee, analyst with RBC Capital Markets, in a research note. Abraxane earned $110 million for Celgene in the second quarter, a year-to-year gain of 16 percent.

Solanki agreed with Yee. "Generally, of course, physicians and regulators want to see OS benefit, and so it could be that Celgene will wait for the OS data before submitting," he told BioWorld Today.

Using dacarbazine as the comparator might provide an edge, since that chemotherapy "has very modest efficacy," Solanki said. "Some key opinion leaders think of dacarbazine almost like a placebo."

As Abraxane continues down melanoma's generally failure-strewn road, recent approvals in metastatic melanoma suggested the level of the FDA's data bar for market clearance.

New York-based Bristol-Myers Squibb Co.'s CTLA-4 blocker Yervoy (ipilimumab), cleared last year, garnered a median OS of 10 months vs. 6 months on adjuvant vaccine (HR = 0.68), and in another trial improved OS benefit in combination with dacarbazine: 11 .2 months for combo vs. 9.1 months for dacarbazine (HR = 0.72). (See BioWorld Today, April 4, 2011.)

Another winner in the melanoma space, later last year, was the kinase inhibitor for patients with the BRAF V600E mutation Zelboraf (vemurafenib, Daiichi Sankyo Co. Ltd. and Roche AG). Zelboraf also boosted OS, with a median survival not reached, as compared to 7.9 months for patients on dacarbazine. (See BioWorld Today, Aug. 18, 2011.)

Expectations for CA033 were "not high," wrote Wells Fargo analyst Brian Abrahams in a research note, and Celgene has chosen to speak only about the timing of its data, rather than regulatory steps and strategy.

What the melanoma outcomes might mean for an ongoing study with Abraxane in pancreatic cancer also is unclear, but Abrahams wrote that no melanoma upside is included in his valuations, though "strong OS data could speak to a larger opportunity."

Oppenheimer analyst Boris Peaker weighed in, citing the approval of Abraxane in breast cancer without OS improvements but with a boost in response rates as compared to ordinary paclitaxel.

Peaker estimated a "reasonable chance" that Abraxane could win the FDA's blessing without more studies, but it's hard to guess, given the lack of full safety and efficacy results from CA033. The breast cancer approval, he wrote in a research note, was based on a response rate of 22 percent for Abraxane vs. 11 percent for paclitaxel. A similar magnitude of improvement, Peaker wrote, might do the trick for the melanoma indication.

Solanki said most oncology opinion leaders are optimistic about Abraxane in melanoma. "In particular, the BRAF wild-type patients have [few] therapeutic options, outside Yervoy, especially as metastatic melanoma has historically been a chemotherapy-resistant disease," he said, calling the Abraxane story "very interesting."

Decision Resources expects Abraxane to win FDA approval and gain use particularly in BRAF-negative/wild type patients in the second-line after Yervoy, or in first-line patients ineligible for Yervoy due to co-morbidities or performance status.

Also, Abraxane could be used to treat BRAF-positive patients who have progressed on a BRAF inhibitor such as Zelboraf, Solanki said.

As for pancreatic cancer, RBC's Yee pegs Abraxane's chances at 30 percent to 35 percent. That trial's primary endpoint is OS, and its design differs importantly from the melanoma study. In pancreatic, Celgene is testing Abraxane plus gemcitabine vs. gemcitabine alone, instead of pitting Abraxane against chemo.