Just shy of four years ago, MEI Pharma Inc. and Helsinn Group hashed out a $464 million deal to develop and commercialize pracinostat. Now an interim futility analysis has persuaded them to halt their phase III study in acute myeloid leukemia (AML) while, pending further evaluation, patients enrolled in other pracinostat studies continue their treatment.

An independent data monitoring committee’s futility analysis demonstrated the trial of pracinostat, an oral histone deacetylase inhibitor, combined with azacitidine in patients with AML who are unfit to receive standard intensive chemotherapy, was unlikely to hit its primary endpoint of overall survival (OS) when compared to a control group. Efficacy concerns, not lack of safety, were cited as the core reason to discontinue.

The decision hit San Diego-based MEI’s stock (NASDAQ:MEIP), as it sagged 18.2% July 2, with shares closing at $3.49. Despite the rough showing, the stock is 49.7% higher than it was on July 3, 2019, when shares went for $2.33 each. The worst showing of the past 12 months for MEI was March 18 when shares closed at 75 cents.

The original deal between MEI and the Helsinn, of Lugano, Switzerland, was struck in August 2016. The agreement gave Helsinn exclusive worldwide rights, including manufacturing and commercialization rights, and responsibility for funding pracinostat’s global development. MEI was to receive near-term payments of $20 million, composed of a $15 million up-front payment and a $5 million payment upon dosing of the first patient in the phase III study of newly diagnosed AML patients unfit to receive induction therapy. MEI is eligible to receive up to $444 million in potential development, regulatory and sales-based milestone payments, along with additional tiered royalty payments in selected territories.

The week before the deal was announced, pracinostat against AML won breakthrough therapy status from the FDA, thanks to a median OS in the phase II trial of 19.1 months and a complete response (CR) rate of 42% (21 of 50 patients). The results, in patients 75 and older or unfit for chemo, compare favorably to a phase III study of Vidaza (azacitidine) in a similar population, which showed a median OS of 10.4 months with Vidaza alone and a CR rate of 19.5%. Generally well-tolerated, the combo turned up with no unexpected toxicities.

The FDA and EMA granted pracinostat orphan drug designation in combination with azacitidine for the treatment of patients with newly diagnosed AML who are 75 or older or unfit for intensive chemotherapy.

The market size for AML is set to expand enormously in the next 10 years, according to DRG, which predicts the $686 million brought in for treatment in the U.S., western Europe and Japan will hit $2.9 billion in 2028. More than half of both the 2018 and 2028 tallies came or will come from the U.S. Market leaders in 2018 were Vidaza from Bristol Myers Squibb Co., Vyxeos (daunorubicin and cytarabine) from Jazz Pharmaceuticals plc and Dacogen (decitabine) from Otsuka Co. Ltd.

Pracinostat is also being evaluated by Helsinn and MEI in an open-label, multicenter phase II study in patients with high or very high-risk myelodysplastic syndromes who are previously untreated with hypomethylating agents. Patients receive a 45-mg dose of pracinostat combined with a 75-mg dose of azacitidine. The primary endpoints are safety and tolerability of pracinostat in combination with azacitidine and overall response rate (ORR), defined as CR plus partial response. Overall survival was a secondary endpoint.

In May, the collaboration released new data from the phase II study showing the combination demonstrated an estimated median OS rate of 23.5 months with a one-year OS rate of 77%. The median follow-up was 17.6 months (range, 15.7–18.8 months) and the ORR was 33% (21/64), all of which are CRs. The clinical benefit rate (CR, mCR plus hematologic improvement [HI], mCR with no HI, or HI with no mCR) was 77% (49/64). Twenty-seven percent of patients (17/64) proceeded to a stem cell transplant while on study. Eleven percent of patients discontinued treatment because of adverse events. The most common grade 3 or higher treatment-emergent adverse events were hematologic, and included decreased neutrophil count (50%), anemia (39%), febrile neutropenia (34%), decreased platelet count (33%), thrombocytopenia (27%) and decreased white blood cell count (20%).

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