Two of the four post-market studies Allos is required to conduct as part of Folotyn 's Sept. 24 accelerated approval could broaden the label of the oncologic, newly cleared for treatment of relapsed or refractory peripheral T-cell lymphoma.

The post-marketing commitments include randomized Phase III trials of Folotyn in both first-line PTCL and in cutaneous T-cell lymphoma.

"It's worked out well," Allos Chief Commercial Officer Jim Caruso said in an interview. "It gives us the opportunity to have further understanding of Folotyn and its clinical utility, and at the same time advance treatment of T-cell lymphoma, as well as add two strategic elements to our three- to five-year product commercialization plan."

The front-line trial has a two stage design. Patients will be enrolled prior to initiating chemotherapy with a CHOP-based regimen; those patients that have either a complete or partial response to CHOP chemotherapy will be transferred to either Folotyn or followed for observation while receiving supportive care. The primary endpoint will be progression-free survival.

The trial in CTCL will compare treatment with Folotyn + Ligand Pharmaceuticals' Targretin (bexarotene) to treatment with Targretin alone in patients refractory to at least one prior systemic therapy. Like the front-line study, this trial is randomized - a trial design that FDA's Oncologic Drugs Advisory Committee voted was necessary for approval of future CTCL drugs (Also see "FDA To Follow EMEA's Lead: ODAC Votes To Require Randomized Controlled Trials For Future Cutaneous T-Cell Lymphoma Drug Approval" - Pink Sheet, 7 September, 2009., p. 18). Targretin is one of four agents indicated to treat CTCL in the U.S.

The other two trials Allos is also required to conduct in the post-approval setting include a Phase I pharmacokinetic study in patients with renal impairment and a Phase I pharmacokinetic/pharmcodynamic trial of Folotyn + Targretin.

The firm has not released details on timing of the trials.

ODAC Endorsement PROPELs Approval Three Weeks Later

Folotyn's accelerated approval was based on overall response rate. No benefit has yet been demonstrated for progression-free survival or overall survival, and under the accelerated approval process it is now Allos' task to confirm that tumor shrinkage actually does predict that patients will live longer.

The approval comes three weeks after ODAC endorsed the orphan indication based on an NDA supported by one, open-label, single-arm, Phase II trial called PROPEL. The study was designed under a Special Protocol Assessment with FDA - an agreement that ensures the agency is on board with the trial design and protocol, but not that it will be satisfied with the ultimate magnitude of benefit shown (Also see "When An SPA Is Not Enough: FDA Will Consider Response Rate For Allos Drug" - Pink Sheet, 6 April, 2009., p. 14).

In PROPEL, that benefit was a 27 percent overall response rate. A key secondary endpoint was duration of response, for which the median was 287 days, or 9.4 months.

ODAC recommended approval of the NDA with a 10-4 vote, agreeing that the drug was active in PTCL, but with concerns that the duration of those responses was weak: only 13 of the 109 evaluable patients maintained that response for more than 14 weeks (Also see "ODAC Backs Allos' Folotyn Despite Fickle Data, Finds Many Paths Forward" - Pink Sheet, 7 September, 2009., p. 19).

FDA's final labeling includes the response duration data in a chart, but does not include any discussion of the findings.

The only additional description of the response findings was that of the responders, 66 percent responded within cycle 1, and the median time to first response was 45 days (range 37-349 days).

The advisory panel also was concerned that the single-arm trial couldn't fully clarify those responses. But the lack of treatment options for PTCL and the difficulty of conducting randomized trials in the setting was not insignificant in their ultimate vote of support, albeit with further investigation in the post-market setting. The outside group endorsed the proposed Phase III study testing Folotyn against placebo following CHOP-based chemotherapy.

One potential benefit of the therapy that came during the panel review but was not included in the product's labeling was its use as bridge therapy to get patients well enough to undergo a stem cell transplant.

With Approval Out Of The Way, Allos Begins Transition To Launch

As Folotyn's approval is Allos' first U.S. indication, it is a transformative event for the firm, which will now add a strong commercial aspect to the organization.

Allos expects to make drug available through a trade launch to health care providers in October, with a sales force of 25 oncology specialists. It will launch the drug commercially in the first quarter of 2010, with a sales force of 50.

Though the company has not released pricing details, the cost of an average course of therapy ranges from $75,000 to $140,000.

Allos has established a reimbursement support program called ASAP (Allos Support for Assisting Patients) similar to that for Genentech's Avastin (bevacizumab), which provides assistance to all patients, regardless of insurance coverage, once an expenditure cap has been met (Also see "Avastin For Lung Cancer Will Be Free To Patients Who Beat The Average" - Pink Sheet, 16 October, 2006., p. 6).

Allos CEO Paul Berns told investors during a Sept. 25 conference call that the company is well-capitalized to execute the four post-market trials, noting that Allos ended the second quarter with approximately $105 million in cash on hand.

- Jamie Hammon (j.hammon@elsevier.com)

Post-Market Requirements Could Broaden Label For Allos' Newly Approved PTCL Drug Folotyn

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