Ariad Pharmaceuticals, Inc. (NASDAQ:ARIA) announced long-term follow-up data from its pivotal Phase 2 PACE clinical trial of Iclusig® (ponatinib), its approved BCR-ABL inhibitor, in heavily pretreated patients with resistant or intolerant chronic myeloid leukemia (CML) or Philadelphiachromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Responses have been maintained long-term in chronic phase CML (CP-CML) patients. The study shows that patients treated with Iclusig continued to demonstrate anti-leukemic activity with a median follow-up of 4.0 years for CP-CML. Additionally, 96 percent of CP-CML patients who underwent ponatinib dose reductions while in response maintained their responses (MCyR) at the four year timepoint.

“We remain very pleased by these continued responses in the PACE study in such a heavily pretreated patient population, as 59 percent of patients had previously received three or more approved tyrosine kinase inhibitors (TKIs). Altogether, 82 percent of CP-CML patients who achieved MCyR are estimated to remain in MCyR at four years,” stated Jorge E. Cortes, M.D., professor and deputy chair, department of leukemia, University of Texas MD Anderson Cancer Center. “These data showing long-term major cytogenic response offer the optimism of favorable outcomes for many patients who previously had no or very limited treatment options available.”

The data were featured at the 21st Conference of the European Hematology Association (EHA) inCopenhagen, Denmark.

PACE Trial Update

The efficacy and safety of ponatinib in CML and Ph+ ALL patients resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation, were evaluated in the PACE trial. A total of 449 patients were treated with ponatinib at a starting dose of 45 mg/day. An estimated 93 percent of patients received two or more approved tyrosine kinase inhibitors (TKIs), and 59 percent of all patients received three or more approved TKIs. Enrollment in the PACE trial was completed in October 2011.

Updated data on CP-CML patients (n=270) from the ongoing trial indicate that with a median follow-up of 48.2 months (data as of August 3, 2015), 110 patients (41%) continued to receive ponatinib. Additional data for CP-CML patients include:

  • 59 percent of CP-CML patients achieved MCyR (primary endpoint) at any time.
    • 82 percent of patients who achieved MCyR are estimated to remain in MCyR at four years by Kaplan-Meier analysis.
  • 39 percent of patients achieved a major molecular response (MMR) or better at any time.
  • By Kaplan-Meier analysis, progression-free survival at four years is estimated to be 56 percent.
  • Overall survival at four years is estimated to be 77 percent.
  • 23 percent of CP-CML patients experienced arterial occlusive events (AOE) that were designated a serious adverse event (SAE), and 29 percent of CP-CML patients experienced any AOE.
  • 4 percent of CP-CML patients experienced a venous thromboembolic SAE, and 5 percent of all patients experienced a venous thromboembolic SAE.
  • The most common any-grade treatment-emergent adverse events occurring in ≥ 20 percent of CP-CML patients included abdominal pain (46%), rash (47%), thrombocytopenia (45%), headache (43%), constipation (41%), and dry skin (42%).

“These data continue to show that ongoing CP-CML patients in the PACE trial have retained long-term cytogenetic and molecular responses at a median of four years follow-up,” stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “We currently have two additional trials underway evaluating Iclusig. Our OPTIC randomized trial evaluating Iclusig at starting doses of 45 mg/day or lower, is currently enrolling patients. Outside the U.S., we initiated our randomized Phase 3 trial of Iclusig in second-line patients with CP-CML called OPTIC-2L in December of 2015 and expect full enrollment in the trial in 2018.”

Efficacy Update Following Dose-Reduction Recommendations

(Data from October 10, 2013 to August 3, 2015)

On October 10, 2013, dose-reduction recommendations were provided by ARIAD to investigators for patients remaining on the PACE trial. The following dose reductions were recommended, unless the benefit-risk analysis warranted treatment with a higher dose:

  • CP-CML patients who already achieved a MCyR should have their ponatinib dose reduced to 15 mg/day,
  • CP-CML patients who had not already achieved MCyR should have their dose reduced to 30 mg/day, and
  • Advanced-phase patients should have their dose reduced to 30 mg/day.

As of August 3, 2015, with an additional 1.9 years (22 months) of follow up after these recommendations, maintenance of response (MCyR) in CP-CML patients was 95 percent (56 of 59) and 100 percent (25 patients), respectively, for patients who were either at 15 mg/day in October 2013 or were reduced to 15 mg/day after October 2013.

  • Of the 69 patients who were in MCyR as of October 10, 2013 and had a dose reduction, 66 patients (96%) maintained their response at 1.9 years following prospective dose reduction.
  • Of the 51 patients who were in MMR as of October 10, 2013 and had a dose reduction, 46 patients (90%) maintained MMR at 1.9 years following dose reduction.
  • 35 patients in MCyR did not undergo any dose reductions (the majority of which were already at a reduced dose of 30 mg/day or 15 mg/day as of October 10, 2013); of these, 33 patients (94%) maintained MCyR after 1.9 more years of ponatinib treatment.

Safety Update Following Dose-Reduction Recommendations (Data from October 10, 2013 to August 3, 2015)

  • Of the patients who underwent dose reduction, six of 75 patients (8%) without prior AOEs had a new AOE during the 1.9-year interval following dose reduction.
  • 31/75 patients reduced from 45 mg to 15 mg
  • 25 /75 patients reduced from 30 mg to 15 mg
  • 19/75 patients reduced either other doses (45 mg to 30 mg or not specified)
  • Of the patients who did not undergo dose reduction, 10 of 62 patients (16%) without prior AOE had a new AOE in the same time interval.

Shares of Ariad Pharmaceuticals closed last Friday at $8.27, down $0.15 or -1.78%. ARIA has a 1-year high of $10.07 and a 1-year low of $4.37. The stock’s 50-day moving average is $7.82 and its 200-day moving average is $6.42.

On the ratings front, Ariad has been the subject of a number of recent research reports. In a report issued on June 6, JMP analyst Michael King reiterated a Buy rating on ARIA, with a price target of $9, which implies an upside of 8.8% from current levels. Separately, on the same day, Cowen’s Chris Shibutani reiterated a Buy rating on the stock and has a price target of $10.

According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Michael King and Chris Shibutani have a total average return of -6.2% and 5.7% respectively. King has a success rate of 42% and is ranked #3349 out of 3892 analysts, while Shibutani has a success rate of 75% and is ranked #1624.

ARIAD Pharmaceuticals, Inc. operates as an oncology company which engages in the discovery, development, and commercialization of small-molecule drugs for the treatment of cancer. Its products include Iclusig and Caregivers. The company was founded by Harvey J. Berger in April 1991 and is headquartered in Cambridge, MA.