Ariad Pharmaceuticals, Inc. (NASDAQ:ARIA) announced clinical data on brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, from the pivotal ALTA trial in ALK-positive (ALK+) non-small cell lung cancer (NSCLC) patients who had experienced disease progression on crizotinib therapy.
As of May 31, 2016, the data show that of patients on the 180-mg regimen with a median follow-up of 11 months, 55 percent achieved confirmed objective response as assessed by the investigator. In this arm, the median progression-free survival (PFS) was 15.6 months in this post-crizotinib setting, by both investigator and independent review committee (IRC) assessment.
Additionally, in this arm, 67 percent of patients with measurable brain metastases achieved a confirmed intracranial objective response, and intracranial PFS was 18.4 months among patients with any brain metastases at baseline. These data will be presented today at the International Association for the Study of Lung Cancer (IASLC) 17thWorld Conference on Lung Cancer (WCLC) being held in Vienna.
“These updated ALTA trial data show that with additional follow-up, median progression-free survival from brigatinib given post-crizotinib is now 15.6 months, and that this is the same whether assessed by the investigators or an independent review committee,” said D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the University of Colorado. “Whether this is a reflection of broader suppression of potential resistance mutations, or its effects on protecting the central nervous system, or both, requires further investigation but by itself these progression-free survival data should be very encouraging for physicians and patients alike. These data really support the idea to pursue brigatinib, not just post-crizotinib, but also in the ongoing ALTA 1L study, which aims to assess its potential in the ALK-treatment naive setting.”
The ALTA Trial
The ALTA (ALK in Lung Cancer Trial of AP26113) trial enrolled 222 patients with ALK+ NSCLC who had been treated with and experienced disease progression on their most recent crizotinib therapy. Patients were randomized one-to-one to receive either 90 mg of brigatinib once per day (QD) (Arm A), or 180 mg QD, preceded by a lead-in dose of 90 mg QD for seven days (Arm B). In addition, patients were stratified by presence of brain metastases at baseline and best response to prior crizotinib therapy.
The primary endpoint of the ALTA trial is investigator-assessed confirmed objective response rate (ORR) as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Key secondary endpoints include PFS, confirmed ORR assessed by an IRC, overall survival (OS), CNS response and PFS, duration of response, safety and tolerability.
Key Data from the ALTA Trial Update
Brigatinib Efficacy and Safety in ALK+ NSCLC Patients:
Clinical Data as of May 31, 2016 with IRC Data as of July 13, 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 a seven-day lead-in at 90 mg and 112 patients in Arm A at the 90-mg dose level). The last patient was enrolled in the study in September 2015.
- The median follow-up was 11 months in Arm B and 10.2 months in Arm A. ALTA trial data presented at the 2016 American Society of Clinical Oncology (ASCO) meeting, as of February 29, 2016, had median follow-up of 8.3 months in Arm B and 7.8 months in Arm A.
- Investigator-assessed confirmed ORR in Arm B was 55 percent. IRC-assessed confirmed ORR in Arm B was 54 percent. Investigator-assessed confirmed ORR in Arm A was 45 percent. IRC-assessed confirmed ORR in Arm A was 49 percent.
- In a subgroup analysis of confirmed ORR by baseline characteristics, there was no difference in confirmed ORR based on prior chemotherapy versus no prior chemotherapy.
- The subgroup analysis by best response to prior crizotinib (partial or complete response versus other) suggests that patients who had achieved partial or complete responses on prior crizotinib treatment had a significantly higher confirmed ORR, compared with patients who did not achieve these responses.
- 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 15.6 months by both investigator assessment and IRC assessment in Arm B. Median PFS was 8.8 months by investigator assessment and 9.2 months by IRC assessment in Arm A.
- Probability of OS at one year was 82 percent and 71 percent in Arm B and Arm A, respectively. The median OS had not been reached in either arm.
- Of the 44 patients with measurable intracranial brain metastases at baseline, the IRC-assessed intracranial ORR was 67 percent (12/18) in Arm B and 46 percent (12/26) in Arm A.
- The median IRC-assessed intracranial PFS was 18.4 months in Arm B and 15.6 months in Arm A.
- The most common treatment-emergent adverse events (TEAEs; ≥ 30% of all patients, [Arm B/A]), regardless of relationship to treatment, were nausea (43%/36%), diarrhea (39%/21%), cough (36%/23%), headache (30%/28%) and increased blood creatine phosphokinase (CPK) (33%/11%).
- TEAEs, grade ≥3, occurring in ≥4 percent of all patients (excluding neoplasm progression; Arm B/A), were increased CPK (10%/3%), hypertension (6%/6%), pneumonia (5%/3%) and increased lipase (3%/5%).
- A subset of pulmonary adverse events (AEs) with early onset (median: Day 2; range: Day 1-9) occurred in six 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 10 percent/three percent and 23 percent/eight percent, respectively. Discontinuations due to documented progressive disease (Arm B/A) were 23 percent and 30 percent.
“We are encouraged by the maturing efficacy and safety profile of brigatinib in this later data cut, which adds three months of follow up compared to the data presented at ASCO,” stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “These data are intended to be submitted to the European Medicines Agency in early 2017 for marketing approval. Pending regulatory review, we expect that brigatinib may become an important therapeutic option for the crizotinib-resistant population.”
The poster presentation, “Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Central Assessment and Updates from ALTA, a Pivotal Randomized Phase 2 Trial,” (Abstract #4046, Poster ID P3.02a-013) will be presented today, Wednesday, December 7, 2016 from 14:30 – 15:45 GMT. (Original Source)
Shares of Ariad Pharmaceuticals closed yesterday at $13.69, up $0.41 or +3.09%. ARIA has a 1-year high of $14.42 and a 1-year low of $4.37. The stock’s 50-day moving average is $10.94 and its 200-day moving average is $9.83.
On the ratings front, Ariad Pharmaceuticals has been the subject of a number of recent research reports. In a report issued on November 30, JMP analyst Michael King reiterated a Hold rating on ARIA. Separately, on November 17, Leerink Swann’s Michael Schmidt reiterated a Buy rating on the stock .
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Michael King and Michael Schmidt have a yearly average return of 0.2% and 28.7% respectively. King has a success rate of 45% and is ranked #2427 out of 4262 analysts, while Schmidt has a success rate of 61% and is ranked #28.
Sentiment on the street is mostly bullish on ARIA stock. Out of 9 analysts who cover the stock, 5 suggest a Buy rating , 2 suggest a Sell and 2 recommend to Hold the stock. The 12-month average price target assigned to the stock is $12.00, which reflects a potential downside of -12% from last closing price.
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.