Spectrum Pharmaceuticals Inc. will use the confirmatory trial for its peripheral T-cell lymphoma (PTCL) drug Beleodaq (belinostat) as the confirmatory trial for the company’s already marketed drug Folotyn (pralatrexate) as well.

The confirmatory trial will provide head-to-head data on the drugs versus standard of care.

“They want to see how the three treatments compare,” CEO Rajesh Shrotriya told “The Pink Sheet” DAILY.

Beleodaq, a histone deacetylase inhibitor (HDAC), was granted accelerated approval July 3, more than a month ahead of the Aug. 9 user fee date, for the treatment of relapsed or refractory PTCL, a rare and fast growing type of non-Hodgkin lymphoma. It was approved based on a Phase II trial that examined tumor response rate and duration of response. Just over one-quarter (25.8%) of the 129-patients in the Phase II study achieved either a complete or partial response.

A confirmatory Phase III trial will look at progression-free survival. In addition to fulfilling the accelerated approval post-marketing requirement for Beleodaq, Spectrum has reached an agreement with FDA to use the same trial to serve the same purpose for the firm’s previously approved PTCL drug Folotyn.

FDA released Spectrum from Folotyn’s two previous PMRs for a Phase III PTCL trial and a Phase III cutaneous T-cell lymphoma trial, the company announced in a regulatory filing July 3. Folotyn, a folate analogue metabolic inhibitor was approved for the same indication in 2009 based on a Phase II trial that examined overall response rate Also see "Post-Market Requirements Could Broaden Label For Allos' Newly Approved PTCL Drug Folotyn" - Pink Sheet, 25 September, 2009..

“We Will Try Our Very Best To Complete This Study”

While the protocol for the new trial is still being finalized with FDA, the company will need to evaluate the comparative efficacy and safety of Beleodaq in combination with the standard-of-care treatment regimen cyclophosphamide/vincristine/doxorubicin/prednisone (CHOP) or Folotyn plus CHOP, versus CHOP alone for initial therapy of patients with PTCL.

The primary endpoint will be PFS, but FDA has not yet told the company the magnitude of benefit that will be needed to confirm the treatment effect. It will involve several hundred patients, Shrotriya said.

Shrotriya said that the company was having difficulty with Folotyn’s previous confirmatory trials due to low enrollment, noting that they were required to study 500 patients.

When asked whether the company was more confident in the feasibility of the new trial, Shrotriya said, “All I can say is that we will try our very best to complete this study.” FDA has several times convened its Oncologic Drugs Advisory Committee to consider the difficulties of completing confirmatory trials for accelerated approvals in cancer Also see "FDA Will Make Advisory Committee Review Of Accelerated Approvals An Annual Event" - Pink Sheet, 14 February, 2011..

Beleodaq has seven other post-marketing requirements six of which are clinical trials including a Phase I dose-finding study that asks them to find the optimal and safe dose of Beleodaq in combination with CHOP. The drug’s label currently includes dosage modification for hematologic and non-hematologic toxicities based on platelet count, and patients with reduced UGT1A1 activity.

“There’s Room For Both”

Shrotriya said it should launch Beleodeq by the end of July but would not comment on pricing. Folotyn has commanded $100,000 per course of treatment Also see "Spectrum Hopes For Synergies With Allos Acquisition Amid Phase III Setback" - Pink Sheet, 5 April, 2012..

Spectrum plans to capitalize on its experience in the PTCL field and is banking on synergies to help it easily market the product.

“We know this market like the back of our hand. We know where the prescribers are. We know where the patients are,” he said.

“There’s room for both” Beleodaq and Folotyn, Chief Operating Officer and President Joe Turgeon said on the company’s first quarter earnings call in May, and there are significant opportunities for cross-promotion. “A sales rep is going to get increased selling time in front of those doctors selling both products, and that's a great thing when you're talking sales.”

He cited FDA’s granting belinostat priority review as one signal of the need for more treatment options in a field where most patients who initially respond to a drug progress within a year and routinely cycle through several lines of therapy.

Sicker Patients Are The Target

Beleodaq will be differentiated from Folotyn and Celgene Corp.’s Istodax (romidepsin), which was approved in 2011 for PTCL patients who received at least one prior therapy, due to its ability to be given to sicker patients with lower platelet counts, Shrotriya said. Other drugs have not been studied in patients with such low platelet counts, the exec explained, noting that Beleodaq’s label indicates that 17% of clinical trial patients had lower than a 100,000 platelet count.

He also said the drug has a relatively better safety profile, saying the drug has a relatively small effect on bone marrow.

There are a number of serious adverse events listed in the drug’s label including warnings about thrombocytopenia, leukopenia and anemia, as well as serious and fatal infections and hepatic toxicity, among others. More than 47% of patients in the Phase II study experienced serious adverse reactions while taking the drug or within 30 days after their last dose.

The company also notes that Belodaq inhibits all three classes of the zinc-dependent HDAC enzymes, differentiating it from Istodax.

And, Shrotriya said, Beleodaq’s label shows the drug has “marked activity” in certain subtypes of patients. For instance, the overall response rate for angioimmunoblastic T-cell lymphoma (AITL) patients was 45.5%.

Credit Suisse analysts estimate Beleodaq will take in $10 million in sales in 2014, $25 million in 2015 and $30 million in 2016 and $2017. This is slightly less than half of their models for Folotyn, which they have taking in $45.9 million in 2015, $48.2 million in 2016 and $50.6 in 2017. Laidlaw & Company forecasted peak sales potential of Beleodaq at $100 million.

Folotyn brought in $44.4 million worldwide in 2013, up from $20.4 million in 2012.

Beleodaq’s approval trigged a $25 million payment to partner Topotarget AS, which licensed the drug to Spectrum in 2010. Topotarget recently merged with France’s Onxeo SA ([A#00140421017]).

The company is also looking at Beleodaq in other indications including non-small cell lung cancer and other solid tumors and hematological malignancies. It has not decided to take any other indication forward to Phase III studies yet.

Spectrum Puts Its Eggs In One Basket: Folotyn, Beleodaq To Share Confirmatory Trial

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