Northwest Biotherapeutics (NWBO) is way overdue disclosing results from an interim analysis of a phase III study of its brain cancer vaccine DCVax.
Twelve weeks have passed since Northwest Bio said independent data monitors were taking their first look at the study, which compares DCVax to placebo in patients with newly diagnosed glioblastoma mutliformae (GBM).
Results from the interim analysis were expected no later than the first week of February, Northwest Bio said. On Feb. 10, Northwest Bio CEO Linda Powers, speaking at the BIO CEO healthcare investor conference, said data monitors needed "another couple of weeks" to complete their work.
We're now another week beyond Power's acknowledged delay and still no word from the company.
Last March -- almost one year ago, actually -- Northwest Bio told investors enrollment in the 312-patient GBM study of DCVax would be completed this quarter or early in the second quarter, and that the first interim analysis would be conducted in the third quarter of 2013.
Northwest Bio spokesperson Farrell Kramer would not disclose the current number of GBM patients enrolled in the DCVax study. "We're not at liberty to provide any information to you that has not been announced publicly," Kramer said, via email.
The DCVax study in GBM has gone through numerous design changes and patient enrollment freezes since it was started in 2005 as a small, non-randomized phase II study expected to enroll 90 patients. In addition to upsizing to 312 newly diagnosed GBM patients, Northwest Bio added a placebo arm to the study and changed its designation to "phase III" -- implying positive results could be used to support an FDA approval filing.
Northwest Bio claims FDA agreed to the changes made the DCVax study but the company does not have a Special Protocol Assessment (SPA) agreement with regulators.
The lack of an SPA is a real concern because Northwest is using a primary endpoint for the DCVAx study -- progression-free survival -- which appears to fall short of FDA's approval standards for therapies addressing newly diagnosed GBM patients.
ImmunoCellular Therapeutics (IMUC) used overall survival as the primary endpoint for a recently completed phase II study of its brain cancer vaccine ICT-107 based on feedback from the FDA.
In a recent shareholder letter, ImmunoCellular stated:
We selected OS as the primary endpoint for clear, pragmatic reasons: to follow the guidance of the FDA relative to what constitutes a registration endpoint, and to inform the design of a phase III registration study. In 2011 written correspondence with our Company regarding our phase II protocol, the FDA indicated "progression free survival (PFS) as an endpoint is acceptable for hypothesis testing, but not as a primary endpoint for a phase 3 trial to support a BLA." Based on FDA's guidance, we focused the trial on generating detailed survival data, and retained PFS as an important secondary clinical endpoint.
Celldex Therapeutics (CLDX - Get Report) is also using overall survival as the primary endpoint for an ongoing phase III study of its brain cancer vaccine rindopepimut.
Northwest Bio has never explained why FDA would agree to review DCVax for approval based on progression-free survival data when two other companies also developing vaccines for newly diagnosed GBM patients said FDA wanted overall survival as the primary endpoint.
The efficacy bar for any interim analysis is always set high, so an announcement from Northwest Bio that the DCVax GBM study is continuing is the most likely outcome of the first interim analysis. However, Northwest Bio should also update investors on the pace of overall enrollment and better explain why a study long-delayed, changed and utilizing a non-approvable primary endpoint can be considered registration worthy.