FDA Approves Alunbrig (brigatinib) for Rare Lung Cancer

On Friday evening, Takeda Pharmaceuticals announced the FDA has approved Alunbrig (brigatinib) to treat patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

Brigatinib is a kinase inhibitor that can be taken orally. The recommended dose is 90 mg orally once daily for the first 7 days. If 90 mg is tolerated during the first 7 days, patient should increase the dose to 180 mg orally once daily. The pill can be taken with or without food.

Brigatinib has an orphan drug designation for this indication and Takeda received an Accelerated Approval of the drug based on tumor response rate and duration of response. An Accelerated Approval means Takeda can market the drug now but additional studies (ie, a phase 3 clinical trial) may be needed by the FDA moving forward.

Efficacy

The FDA approval was based largely on the Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial of brigatinib in adults. This ongoing, two-arm, open-label, multicenter trial enrolled 222 patients with locally advanced or metastatic ALK+ NSCLC who had progressed on crizotinib.

Patients received either 90 mg of brigatinib once daily (n=112) or 180 mg once daily following a seven-day lead-in of 90 mg once daily (n=110). The major efficacy outcome measure was confirmed overall response rate (ORR) as evaluated by an Independent Review Committee (IRC).

With a median follow-up of 8 months (range 0.1 - 20.2), results demonstrated that of the patients who received the recommended dosing regimen (90→180 mg), 53% achieved a confirmed overall response (OR with a median duration of response of 13.8.

Table: Efficacy

Outcome Measure	90 mg daily (n=112)	90 mg →180 mg (n=110)
Overall Response Rate Complete Response Partial Response Duration of Response	48% 3.6% 45% 13.8 months	53% 4.5% 48% 13.8 months

 The drug was also effective in patient who had their cancer metastasized to the brain. At the recommended dosing regimen, 67% of patients with measurable brain metastases (n=18) achieved a confirmed intracranial OR by IRC.

Table: Efficacy in Patients with Brain Metastases

Outcome Measure	90 mg daily (n=26)	90 mg →180 mg (n=18)
Intracranial ORR Complete Response Partial Response Duration of Response	42% 7.7% 35% Not estimated	67% 0 67% 5.6 months

Safety

Serious adverse reactions occurred in 38% of patients in the 90 mg group and 40% of patients in the 90→180 mg group. The most common serious adverse reactions were pneumonia (5.5% overall, 3.7% in the 90 mg group, and 7.3% in the 90→180 mg group) and ILD/pneumonitis (4.6% overall, 1.8% in the 90 mg group and 7.3% in the 90→180 mg group). Fatal adverse reactions occurred in 3.7% of patients and consisted of pneumonia (2 patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis and urosepsis (1 patient each).

At the recommended dosing regimen, the most common adverse reactions (≥25%) were nausea, diarrhea, fatigue, cough, and headache.

Warnings and Precautions

The drug does come with warnings and precautions. The drug has been associated with interstitial lung disease (ILD)/pneumonitis, hypertension, bradycardia, visual disturbance, creatine phosphokinase (CPK) elevation, pancreatic enzyme elevation, hyperglycemia and embryo-fetal toxicity. Please see the prescribing information for further details.

NSCLC Community Thrilled with the Approval News

In a news release, D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the University of Colorado said, “In recent years, small molecule ALK inhibitors have revolutionized the treatment options for those with advanced ALK+ non-small cell lung cancer. Nevertheless, there is still a need for additional ALK inhibitors like brigatinib (Alunbrig), which have a manageable safety profile and may address mechanisms of clinical resistance to crizotinib, including progression in the central nervous system.”

Dr Camidge added, “The ALTA trial showed that brigatinib (ALUNBRIG) was highly effective post-crizotinib with the majority of patients who received 180 mg once daily with a seven-day lead in at 90 mg once daily achieving an overall response and a median duration of response greater than one year. Importantly, the extent of activity among those with brain metastases was also notable.”

Bonnie Addario, founder and chair of the Addario Lung Cancer Foundation stated, “For patients with ALK+ metastatic NSCLC who have progressed on or are intolerant to crizotinib, who are facing the uncertainty of disease progression and the potentially devastating impact of brain metastases, the approval of Alunbrig offers a new hope.”

Finally, Andy Plump, M.D., Ph.D., Takeda Chief Medical and Scientific Officer commented on the ability of the research community to develop a drug that could get Accelerated Approval so quickly. Dr Plump stated, “The rapid development of Alunbrig is a tribute to the dedication of many research scientists and clinicians who carefully designed and developed this new medicine to address unmet medical needs in the ALK+ NSCLC patient population. Most importantly, we would like to thank the patients and families who participated in the clinical trials.”

About ALK+ NSCLC

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer is not considered a rare cancer. However, approximately 2 – 8% of patients with NSCLC have a rearrangement in the ALK gene.

About 70% patients with ALK+ NSCLC who progress following first-line ALK inhibitor therapy develop brain metastases.

Saturday, Apr 29, 2017

Source: http://www.raredr.com/