Takeda to Present Results from the Phase 3 TOURMALINE-AL1 Trial of NINLARO in Patients with Amyloidosis

Oral Presentation at the American Society of Hematology (ASH) Annual Meeting on December 7, 2019 

Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) today announced that results of the TOURMALINE-AL1 trial will be presented during an oral session at the 61st American Society of Hematology (ASH) annual meeting on Saturday, December 7, 2019 in Orlando, Florida. TOURMALINE-AL1 is a Phase 3, randomized clinical trial evaluating the effect of NINLAROTM (ixazomib) in combination with dexamethasone in patients with relapsed or refractory systemic light-chain (AL) amyloidosis.

The TOURMALINE-AL1 trial did not meet the first of the two primary endpoints of significant improvement in overall hematologic response, as reported in June 2019. Hematologic responses were seen in 53% versus 51% of patients receiving NINLARO plus dexamethasone versus physician’s choice (odds ratio 1.10 [95% CI 0.60-2.01], p=0.762) as assessed by an Adjudication Committee (AC). The second primary endpoint of two-year vital organ deterioration or death was not mature at the time of analysis. Other endpoints studied including vital organ progression free survival (PFS), hematologic PFS, time to treatment failure and time to subsequent therapy were numerically higher in the NINLARO plus dexamethasone arm compared to the physician’s choice arm. Takeda is committed to making data available to researchers to continue investigation of this disease. NINLARO is not approved as a treatment for AL amyloidosis.

“AL amyloidosis is a rare condition, for which prognosis and patient outcomes are poor. Current treatments are often retrofitted from therapies used for multiple myeloma,” said Angela Dispenzieri, MD, Mayo Clinic, and the trial’s principal investigator and lead author. “For a Phase 3 study that did not meet its primary endpoint, this trial provides interesting information for this community and for future studies. Ongoing research and development to investigate potential treatment options for this underserved patient population is critical.”

“We look forward to the opportunity to share the data from the TOURMALINE-AL1 trial,” said Phil Rowlands, Head of Oncology Clinical Research and Development, Takeda. “We are confident that sharing our findings with the community will help encourage conversations around the need for continued research to address the needs that remain in this patient population.”

“There are serious unmet needs for people living with amyloidosis. AL amyloidosis is a progressive and fatal disease; many patients are diagnosed late, significantly impacting life expectancy. The challenges associated with developing drugs for this disease make continued research and development for treatment critical,” said Isabelle Lousada, Founder and CEO of the Amyloidosis Research Consortium. “The data from TOURMALINE-AL1 provide valuable insights to researchers as they select endpoints for future amyloidosis studies, and knowledge that will provide context in future drug reviews and approvals, ultimately aiding in providing treatment options for patients.”

Primary Results from the Phase 3 TOURMALINE-AL1 Trial of Ixazomib-Dexamethasone Versus Physician’s Choice of Therapy in Patients (Pts) with Relapsed/Refractory Primary Systemic AL Amyloidosis (RRAL). Saturday, December 7, 9:30 a.m., Orange County Convention Center, Hall E1.

Key findings, to be presented by Dr. Angela Dispenzieri, include:

  • The first of two primary endpoints was not met in TOURMALINE-AL1. Hematologic responses were seen in 53% versus 51% of patients receiving NINLARO plus dexamethasone versus physician’s choice (odds ratio 1.10 [95% CI 0.60-2.01], p=0.762).
  • Complete response (CR) rate was 26% in the NINLARO plus dexamethasone arm versus 18% in the physician’s choice arm.
  • The second primary endpoint, two-year vital organ deterioration or death, was not mature at the time of analysis.
  • Other endpoint data as assessed by investigators includes:
    • Median duration of hematologic response was 46.5 months in the NINLARO plus dexamethasone arm and 20.2 months in the physician’s choice arm as assessed by investigators.
    • Vital organ PFS was 18.0 months in the NINLARO plus dexamethasone arm and 11.0 months in the physician’s choice arm.
    • Hematologic PFS was 20.1 months in the NINLARO plus dexamethasone arm and 16.7 months in the physician’s choice arm.
    • Time to treatment failure was 10.1 months in the NINLARO plus dexamethasone arm and 5.2 months in the physician’s choice arm.
    • Time to subsequent therapy was 26.5 months in the NINLARO plus dexamethasone arm and 12.5 months in the physician’s choice arm.
  • At data cut-off, patients had received a median treatment duration of 11.7 versus 5.0 months on the NINLARO plus dexamethasone versus physician’s choice arms.
  • Safety data includes:
    • Drug-related adverse events (AE) were experienced by 82% of patients receiving NINLARO plus dexamethasone compared to 81% of patients receiving physician’s choice.
    • Serious adverse events (SAE) were experienced by 47% of patients in the NINLARO plus dexamethasone arm compared to 33% in the physician’s choice arm.
    • Discontinuation of treatment due to AEs was 26% in the NINLARO plus dexamethasone arm compared to 20% in the physician’s choice arm.
    • Common any grade AEs in both the NINLARO plus dexamethasone arm and physician’s choice arm included fatigue (45% and 43%), peripheral edema (46% and 32%), diarrhea (34% and 30%), insomnia (38% and 17%), rash (33% and 20%), constipation (21% and 26%), dyspnea (24% and 19%), upper respiratory tract infection (24% versus 16%), nausea (24% versus 14%) and peripheral neuropathy (19% versus 15%).
    • Common (≥5% overall) grade ≥3 AEs were fatigue (9% versus 9%), peripheral edema (5% versus 5%), rash (4% versus 5%) and dyspnea (6% versus 4%).
    • 6% of patients in the NINLARO plus dexamethasone arm and 5% of patients in the physician’s choice arm died on study. All deaths were considered to be related to AL amyloidosis or complications thereof.
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