Ariad Pharmaceuticals, Inc. (NASDAQ:ARIA) announced updated clinical data on brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, from the pivotal ALTA trial in patients who had experienced disease progression on crizotinib therapy. The data show that, of patients on the 180 mg regimen (Arm B) with a median follow-up of 8.3 months, 54 percent achieved a confirmed objective response, the trial’s primary endpoint. In this arm, the median progression free survival (PFS) exceeded one year (12.9 months) in this post-crizotinib setting. Additionally, a 67 percent confirmed intracranial objective response rate (ORR) was achieved in patients with measurable brain metastases. These data will be presented today, for the first time, at the Annual Meeting of the American Society of Clinical Oncology (ASCO), reflecting an additional 12 weeks of patient follow up and new data on central nervous system (CNS) activity compared to the abstract released last month.
“Most patients with ALK-positive non-small cell lung cancer who are treated with crizotinib eventually experience disease progression, often due to acquired ALK resistance mutations or metastases in the central nervous system,” said presenting author Dong-Wan Kim, M.D., Ph.D., head of the Cancer Clinical Trials Center at the Seoul National University Hospital in South Korea. “For these patients, we are very excited by the brigatinib ALTA trial data, which showed compelling efficacy and safety data, including complete responses and activity in the CNS.”
The ALTA trial
The primary endpoint of the ALTA (ALK in Lung Cancer Trial of AP26113) trial is investigator-assessed confirmed objective response rate (ORR) as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Key secondary endpoints include progression free survival (PFS), confirmed ORR assessed by an independent review committee (IRC), CNS response (IRC-assessed intracranial ORR and PFS), overall survival, safety and tolerability. Brigatinib was granted the U.S. Food and Drug Administration (FDA) Orphan Drug designation for ALK+ non-small cell lung cancer (NSCLC) and the FDA Breakthrough Therapy designation for the treatment of patients with ALK+ non-small cell lung cancer (NSCLC) that is resistant to crizotinib.
The trial enrolled 222 patients with ALK+ NSCLC who had been treated with and experienced disease progression on crizotinib. Patients were randomized one-to-one to receive either 90 mg of brigatinib once per day (QD) (Arm A), or 180 mg QD with a seven day lead-in at 90 mg QD (Arm B).
In addition, patients were stratified by the presence of brain metastases at baseline and best response to prior crizotinib.
Key Data from the ALTA Trial
Brigatinib Efficacy and Safety in ALK+ NSCLC Patients:
Data as of February 29, 2016
- A total of 222 patients with ALK+ NSCLC treated with prior crizotinib therapy were randomized in the study (110 patients in Arm B at the 180 mg dose level with 7-day lead-in at 90 mg and 112 patients in Arm A at the 90 mg dose level). The last patient enrolled in the study in September 2015.
- The median follow-up was 8.3 months in Arm B (range 0.1—20.2) and 7.8 months in Arm A (range 0.1—16.7).
- Investigator-assessed confirmed ORR in Arm B was 54 percent, including four complete responses. Confirmed ORR in Arm A was 45 percent, including one complete response.
- Responses in Arm B included a confirmed partial response in a patient with the ALK kinase domain G1202R mutation at baseline, which is associated with resistance to all approved tyrosine kinase inhibitors (TKIs).
- Median PFS was 12.9 months and 9.2 months in Arm B and Arm A, respectively. Probability of overall survival (OS) at 1-year was 80 percent and 71 percent in Arm B and Arm A, respectively.
- An evaluation of the efficacy of brigatinib in ALK+ NSCLC patients with intracranial CNS metastases at baseline was also included in the ASCO presentation.
- In an independent central review of brain magnetic resonance imaging (MRI) scans, 18 patients in Arm B and 25 patients in Arm A were identified as having measurable CNS metastases at baseline.
- Among patients with measurable CNS metastases at baseline, the IRC-assessed confirmed intracranial ORR was 67 percent (12/18) in Arm B and 36 percent (9/25) in Arm A; among the subset of patients with measurable, active brain metastases, confirmed intracranial ORR was 73 percent (11/15) in Arm B and 36 percent (7/19) in Arm A. Measurable, active brain metastases are defined as having had no prior radiotherapy or progression following radiotherapy.
- Median intracranial PFS for patients with intracranial CNS metastases at baseline was not yet reached in Arm B and was 15.6 months in Arm A.
- The most common treatment-emergent adverse events (TEAEs; ≥ 25% of all patients, [Arm B/A]), regardless of relationship to treatment, were nausea (40%/33%), diarrhea (38%/19%), cough (34%/18%), and headache (27%/28%).
- TEAEs, ≥ grade 3, occurring in ≥ 5 percent of all patients (Arm B/A), were increased blood creatine phosphokinase (9%/3%) and hypertension (6%/6%).
- A subset of pulmonary adverse events with early onset (median: Day 2; range: Day 1-9) occurred in 6 percent of all patients (≥ grade 3 in 3% of patients); no such events with early onset occurred after dose escalation to 180 mg QD in Arm B.
- Discontinuations and dose reductions due to AEs (Arm B/A) were 8 percent/3 percent and 20 percent/7 percent, respectively. Discontinuations due to progressive disease (Arm B/A) were 17 percent and 30 percent.
“The ALTA trial data support our planned NDA submission with a recommendation for dosing with 180 mg once daily following a seven-day lead-in at 90 mg. We are on track for submission in the third quarter,” stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “We believe brigatinib’s antitumor activity both on disease in the lungs and in the central nervous system, safety profile, and once-daily dosing regimen taken with or without food, provide the potential for brigatinib to be an important new therapeutic option for the crizotinib-resistant patient population.” (Original Source)
Shares of Ariad closed last Friday at $8.98, up $0.07 or 0.79%. 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 $7.63 and its 200-day moving average is $6.34.
On the ratings front, Ariad has been the subject of a number of recent research reports. In a report issued on May 24, Jefferies Co. analyst Eun Yang reiterated a Buy rating on ARIA, with a price target of $13, which represents a potential upside of 44.8% from where the stock is currently trading. Separately, on May 23, William Blair’s Y Katherine Xu 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, Eun Yang and Y Katherine Xu have a total average return of -2.9% and 4.2% respectively. Yang has a success rate of 60% and is ranked #3379 out of 3894 analysts, while Xu has a success rate of 49% and is ranked #1056.
Overall, one research analyst has rated the stock with a Sell rating, 4 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 $10.00 which is 11.4% above where the stock closed last Friday.
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.