Ariad Pharmaceuticals, Inc. (NASDAQ:ARIA) announced long-term follow up from its pivotal Phase 2 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). The study now shows that with a median follow-up of approximately 3.5 years for chronic phase CML (CP-CML) patients and a median follow-up of approximately 2.9 years in all patients in the trial, Iclusig continues to demonstrate anti-leukemic activity in patients with limited treatment options. Responses have been maintained long-term in CP-CML patients. Eighty-three percent (83%) of CP-CML patients who achieved a major cytogenetic response (MCyR) are estimated to remain in MCyR at three years.
Additionally, 95 percent of CP-CML patients who underwent ponatinib dose reductions maintained their responses (MCyR). Benefit-risk evaluations should guide the decision to initiate and maintain Iclusig therapy, particularly in patients who may be at increased risk for arterial occlusive events (AOE).
“These continued responses in the PACE study, with a minimum follow-up of 3.3 years, in such a heavily pretreated patient population are very encouraging. Eighty-three percent of CP-CML patients who achieved the primary endpoint of major cytogenetic response remain in MCyR at three years,” stated Jorge E. Cortes, M.D., Professor and Deputy Chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center. “Careful assessment of the benefit and risk of initiating ponatinib therapy, particularly in patients who may be at increased risk for arterial occlusive events, can help identify patients with refractory Ph+ leukemias who can benefit most from this treatment.”
The data were featured today at the 20th Conference of the European Hematology Association (EHA) in Vienna, Austria.
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 pivotal Phase 2 PACE trial. A total of 449 patients were treated with ponatinib at a starting dose of 45 mg/day. Ninety-three percent of patients had previously received two or more approved tyrosine kinase inhibitors (TKI), and 55 percent had previously received three or more approved TKIs.
Updated data on CP-CML patients (n=270) from the ongoing trial indicate that with a median follow-up of 42.3 months (data as of February 2, 2015), 114 patients (42%) continue to receive ponatinib. Additional data in CP-CML patients include:
- 59% of CP-CML patients achieved MCyR (primary endpoint) at any time.
- 83% of patients who achieved MCyR are estimated to remain in MCyR at 3 years.
- 39% of patients achieved a major molecular response (MMR) or better.
- By Kaplan-Meier analysis, progression-free survival at 3 years is estimated to be 60%.
- Overall survival at 3 years is estimated to be 81%.
- 23% of CP-CML patients experienced an AOE designated a serious adverse event (SAE), and 28 percent of CP-CML patients experienced any AOE. The median time to onset for AOEs in CP-CML patients was 14.1 (0.3–44.0) months.
- 4% and 5% of CP-CML patients, respectively experienced a venous thromboembolic SAE or AE.
- The most common all-grade treatment-emergent adverse events occurring in ≥ 40% of CP-CML patients were abdominal pain (46%), rash (46%), thrombocytopenia (45%), headache (43%), constipation (41%), and dry skin (41%); the discontinuation rate due to adverse events was 18% in CP-CML.
“These data show that the majority of CP-CML patients in the PACE trial retained their anti-leukemic responses, even when lowering the daily dose of Iclusig,” stated Frank G. Haluska, M.D., Ph.D., senior vice president of clinical research and development and chief medical officer at ARIAD. “The safety and efficacy of Iclusig at starting doses lower than 45 mg will be studied in the randomized OPTIC (Optimizing Ponatinib Treatment InCML) trial set to begin shortly.”
Efficacy Update Following Prospective Dose-Reduction Recommendations
(Data from October 10, 2013 to February 2, 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 February 2015, with 1.3 years (16 months) of follow-up after these recommendations, the rate of maintenance of response in CP-CML was 95% — whether or not patients underwent prospective dose reductions.
- Of the 64 patients who were in MCyR as of October 10, 2013 and had a prospective dose reduction, 61 patients (95%) maintained their response at 1.3 years following prospective dose reduction.
- Of the 47 patients who were in MMR as of October 10, 2013 and had a prospective dose reduction, 44 patients (94%) maintained their response at 1.3 years following prospective dose reduction.
- 42 patients in MCyR did not undergo any dose reductions (the majority of which were already at a reduced dose of 30 mg or 15 mg as of October 10, 2013); of these, 39 patients (93%) maintained MCyR after 1.3 more years of ponatinib treatment.
Safety Update Following Prospective Dose-Reduction Recommendations (Data from October 10, 2013 toFebruary 2, 2015)
- Of the patients who underwent prospective dose reduction, 5 of 71 patients (7%) without prior AOEs had a new AOE during the 1.3 year interval following prospective dose reduction.
- Of the patients who did not undergo prospective dose reduction, 9 of 67 patients (13%) without prior AOE had a new AOE in the same time interval. (Original Source)
Shares of Ariad Pharmaceuticals opened today at $8.82 and are currently trading down at $8.74. ARIA has a 1-year high of $9.89 and a 1-year low of $4.90. The stock’s 50-day moving average is $9.02 and its 200-day moving average is $7.85.
On the ratings front, Ariad has been the subject of a number of recent research reports. In a report issued on June 3, William Blair analyst Tim Lugo reiterated a Buy rating on ARIA, with a price target of $11, which implies an upside of 24.7% from current levels. Separately, on May 14, BMO’s Jim Birchenough reiterated a Buy rating on the stock and has a price target of $14.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Tim Lugo and Jim Birchenough have a total average return of -1.7% and 40.6% respectively. Lugo has a success rate of 50.0% and is ranked #2963 out of 3623 analysts, while Birchenough has a success rate of 63.6% and is ranked #18.
Overall, 2 research analysts have assigned a Hold rating and 2 research analysts have given a Buy rating to the stock. When considering if perhaps the stock is under or overvalued, the average price target is $10.50 which is 19.0% above where the stock opened today.
ARIAD Pharmaceuticals Inc is an oncology company. The Company is engaged in transforming the lives of cancer patients with breakthrough medicines. It commercializes & develops products and product candidates including Iclusig, Brigatinib, and AP32788.