Partial return of pacritinib likely.
FDA offers to tell all…with CTI’s permission.
CTI BioPharma declines.
February 29, 2016…. Richard Pazdur, the FDA’s oncology chief, offered to discuss openly reasons for placing a hold on pacritinib provided CTI authorized, in writing, the FDA’s disclosure of any and all clinical results.
CTI provided various reasons for its refusal. “The FDA,” said Senior VP Monique Greer, “has not yet shared its findings with CTI and the company has not seen the PERSIST2 data.”
Moreover, “unblinding the data prior to locking it down would place the study in jeopardy,” said Jack W. Singer, MD, CTI Chief Scientific Officer.
The clinical trial’s independent Data Safety Monitoring Committee, according to Singer, MD, concluded the trial should continue. There are confirming reports of this conclusion. The DMSC reportedly also expressed concern over bleeding issues and sought more rigorous monitoring.
Only those with thrombocytopenia (platelet count ≤ 100,000/µL) qualified for the trial. Without close scrutiny of the data – and perhaps even afterward — it is difficult to say whether myelofibrosis or pacritinib is responsible for bleeding and deaths on the clinical trial.
The bottom line: Pacrinitib is a drug that helps some and possibly harms others. Without hearing from the FDA why this Phase III drug that met with approvals through all its clinical trial stages was hit with a partial clinical hold and shortly afterward a full ban, we cannot know the full risk/benefit picture.
And without authorization from CTI BioPharma, the FDA will be unable to explain its actions despite the agency’s “frustration…at its inability to disclose” this information in the absence of formal, written consent by CTI BioPharma.
Without exception, every investigator we spoke with believes those patients who were deriving benefit from pacritinib should be allowed to continue taking the drug. Many have been in touch with the FDA formally requesting immediate resumption of pacritinib to that population.
The reported FDA gesture – return to the partial hold of February 4 which would make pacritinib available to those already benefiting from the drug — has a morass of administrative detail attached.
Today, Singer said the company would present the FDA-requested revised consent form to the agency “early this week” and a proposal broadening the application to make the path for qualified patients to acquire pacritnib easier.
Unless there are revisions to the current FDA proposal, as it now stands each patient would have to qualify separately, acquire an independent NDA, and get approval of an Institutional Review Board. Moreover, none of this would apply to European patients.
Unfortunately for those with MF and very low platelet levels, there do not appear to be any good alternative meds.
Pacritinib is an oral tyrosine kinase inhibitor targeting two MPN mutations, JAK2 and CD135 or FLT-3, a protein frequently mutated in acute myeloid leukemia. The drug was widely seen as a possible alternative to Jakafi for myelofibrosis patients with very low platelets or anemia. After completing its Phase III PERSIST-I clinical trials, reported on favorably at ASCO and ASH in 2015, CTI readied its application for FDA approval in January, 2016.
After evaluation of PERSIST-2 trial data, the FDA placed a partial clinical hold on the drug February 4 followed on February 8 with a full clinical hold, essentially banning all use of the drug. Two weeks later FDA approached CTI to explore restoring the partial ban permitting pacritinib use by those clinical trial patients benefiting from the drug.
Contact FDA: Toll Free (855) 543-3784, firstname.lastname@example.org
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