Spectrum Pharmaceuticals Inc.'s endpoint-beating success in the pivotal Phase II study with belinostat for relapsed/refractory peripheral T-cell lymphoma (PTCL) keeps the firm on track potentially to pair the pan-histone deacetylase (HDAC) inhibitor with Spectrum's antifolate Folotyn (pralatrexate), already approved for the condition.

"PTCL is still a small market, and this puts a cap on sales, however good the results," Decision Resources analyst Lisa Murch told BioWorld Today.

In September, when Henderson, Nev.-based Spectrum disclosed positive top-line results from the trial known as BELIEF, Murch called them "not a game changer" for belinostat, because of the narrow market.

Another FDA-cleared player in PTCL is Summit, N.J.-based Celgene Corp.'s Istodax (romidepsin). Adnan Butt, analyst with RBC Capital Markets, wrote in a research report that belinostat shows promise as a stand-alone or combo drug with Folotyn, acquired in Spectrum's buyout of Allos Therapeutics Inc., of Westminster, Colo. (See BioWorld Today, April 6, 2012.)

Folotyn and Istodax sales add up to about $100 million annually, Butt wrote, and belinostat could grow that number by more than 50 percent if approved.

Decision Resources' Murch said the company "will need to develop [belinostat] in larger indications for forecasts to be substantially increased upwards," a task that "might be easier, once it is approved for PTCL."

Full results from the BELIEF trial surpassed an objective response rate of at least 20 percent, the study's primary efficacy endpoint as established under a special protocol assessment agreement with the FDA, according to Spectrum, which entered a potential $350 million deal with Copenhagen, Denmark-based TopoTarget A/S for belinostat in 2010.

The complete safety evaluation of belinostat has been accepted for presenting at the T-Cell Lymphoma Forum in San Francisco in late January, Spectrum said.

Butt predicted Spectrum will submit a new drug application around the middle of next year, followed by approval in 2014. "Although PTCL remains an unmet need needing new drug approvals, we conservatively assume a standard review cycle, given that Folotyn and Istodax are already approved," he wrote, calling the likelihood of market clearance high.

Murch, asked about other PTCL candidates that show promise, cited MLN8237 (alisertib), from Cambridge, Mass.-based Millennium: The Takeda Oncology Co., which entered Phase III trials in March.

Likely to launch in 2018, Murch said, MLN8237 is the first Aurora A kinase inhibitor to reach late-stage testing, and has shown a response rate of 57 percent against PTCL in Phase II studies. "Again, I would expect Takeda to expand this out into larger indications," she said.

MLN8237 already was under investigation for a broad range of cancers, including B-cell and T-cell non-Hodgkin lymphoma and solid tumors when the Phase III trial in PTCL started, with overall response rate and progression-free survival as endpoints.

Meanwhile, belinostat is one of the higher profile HDAC inhibitors in a space that's growing hotter. Over the summer, MEI Pharma Inc., of San Diego, disclosed plans to acquire Singapore-based S*BIO Pte Ltd.'s exclusive worldwide rights to pracinostat, an oral HDAC inhibitor of interest for hematologic diseases, such as acute myeloid leukemia and myelofibrosis, and solid tumors. (See BioWorld Today, Aug. 15, 2012.)

MEI said it would issue $500,000 of common stock to S*BIO, and will commit to success-based clinical, regulatory and sales milestone payments up to $75.2 million, plus low, single-digit royalties. MEI snatched up the drug to complement its portfolio of isoflavone-based drug candidates.

Boston-based Acetylon Pharmaceuticals Inc. formed around work done at the Dana-Farber Cancer Institute and Harvard University.

The company's lead candidate, ACY-1215, is an oral, selective HDAC6 inhibitor for relapsed and relapsed/refractory multiple myeloma. Earlier in the year, Celgene made a $15 million investment in the company. (See BioWorld Today, Feb. 10, 2012.)

Spectrum's stock (NASDAQ:SPPI) closed Friday at $11.72, up 42 cents.