On November 20, 2015 Takeda reported that the U.S. Food and Drug Administration (FDA) has approved NINLARO (ixazomib) capsules, the first and only oral proteasome inhibitor, indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy (Press release, Takeda, NOV 20, 2015, View Source [SID:1234508305]).

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NINLARO is a once-weekly pill. More information is available at www.NINLARO.com.

Takeda submitted a New Drug Application for NINLARO to the FDA in July 2015, and in September NINLARO was granted Priority Review status with a PDUFA date of March 10, 2016, reflecting the profound and continuing unmet need for new treatments for multiple myeloma, a devastating, relapsing and incurable rare cancer.

"With the approval of NINLARO, we can now offer patients a once-weekly oral proteasome inhibitor as part of a highly active triplet therapy," said Paul Richardson, M.D., Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center Institute Physician at Dana-Farber Cancer Institute, and investigator for TOURMALINE-MM1, the pivotal Phase 3 trial on which today’s approval is based. "We, as investigators of the TOURMALINE-MM1 trial, felt it was vital to conduct a comprehensive ‘real world’ evaluation of this combination that included some of the most common patient types in the relapsed/refractory multiple myeloma setting, such as older patients, patients with moderate renal impairment, light chain disease, and high risk cytogenetics. Further, we treated patients until disease progression to determine the sustainability of NINLARO in treating their relapsed/refractory disease. The TOURMALINE-MM1 data demonstrate convincingly that oral NINLARO-based triplet treatment is effective at extending progression-free survival, over and above the clinical benefit seen with lenalidomide and dexamethasone, with a tolerable safety profile."

"We introduced the first proteasome inhibitor for multiple myeloma, VELCADE, into clinical research approximately 20 years ago. Since that time, we’ve significantly advanced scientific understanding of this rare cancer, culminating in the introduction of NINLARO," said Andy Plump, M.D., Ph.D, Takeda Chief Medical and Scientific Officer. "NINLARO is an entirely new molecule that offers the efficacy of this proteasome inhibitor in a convenient once-weekly pill with a tolerable safety profile. Takeda is delighted to bring this significant innovation to multiple myeloma patients today, and we continue to examine the potential of NINLARO through a robust clinical development program."

Dr. Brian Durie, Chairman of the International Myeloma Foundation, said, "The IMF is pleased by the approval of ixazomib. This opens the door for a fully oral proteasome inhibitor-based triplet combination therapy. Having worked in multiple myeloma for decades, I’ve seen notable progress, yet significant unmet needs remain. With today’s approval, we now have another attractive option for many patients living with multiple myeloma."

The FDA approval of NINLARO is based on results from the TOURMALINE-MM1 Phase 3 clinical trial, the first double-blind, placebo-controlled trial with a proteasome inhibitor. TOURMALINE-MM1 is the first of five ongoing Phase 3 clinical trials with study results available. The TOURMALINE program has enrolled approximately 3,000 patients to date in 40 countries. Data from the NINLARO Phase 3 TOURMALINE-MM1 pivotal trial will be presented at the upcoming 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) on December 7, 2015.

"The approval of ixazomib offers a much-needed additional option in the multiple myeloma treatment landscape. It is developments such as these that help us to better understand the disease and provide continued hope for patients," said Kathy Giusti, Founder and Executive Chairman of the Multiple Myeloma Research Foundation (MMRF). "A cancer diagnosis today is different from what it was just a few years ago and it’s exciting to see continued progress. As a patient, I understand the urgent need for advancing research through partnerships that bring new treatment options, as we’ve done with Takeda."

"NINLARO is a first-of-its-kind innovation that is supported by a global development program, unprecedented for us at Takeda Oncology, and we would like to express our immense appreciation for all patients involved for their incredible strength and invaluable participation. The introduction of NINLARO marks an important step forward, as its efficacy and safety profile – coupled with its completely oral administration – potentially can reduce some logistical burdens, and help enable patients to reap the full benefits of this sustainable therapy," explained Christophe Bianchi, M.D., President, Takeda Oncology. "As part of our unwavering 20-year commitment, Takeda will continue to pursue advances for these patients, and we look forward to introducing and expanding access to NINLARO in other markets around the world."

About the TOURMALINE-MM1 Trial

TOURMALINE-MM1 is an international, randomized, double-blind, placebo-controlled clinical trial of 722 patients, designed to evaluate NINLARO plus lenalidomide and dexamethasone compared to placebo plus lenalidomide and dexamethasone in adult patients with relapsed and/or refractory multiple myeloma. Results showed NINLARO is effective in extending Progression Free Survival (PFS) and has a manageable safety profile. The trial achieved its primary endpoint and demonstrated a clinically meaningful and statistically significant prolongation in PFS at this analysis, which showed that patients treated in the NINLARO arm lived without their disease worsening for a significantly longer time compared to patients in the control arm. Patients continue to be treated to progression in this trial and will be evaluated for long term outcomes.

In the TOURMALINE-MM1 trial, the most common adverse reactions (≥20%) in patients receiving NINLARO included diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting and back pain. Serious adverse reactions reported in ≥2% patients included thrombocytopenia (2%) and diarrhea (2%).

Efficacy and safety data were reviewed by an Independent Data Monitoring Committee (IDMC), who recommended the study be continued in blinded fashion to allow further maturation of long term outcomes, including overall survival (OS) and long-term safety.

On November 20, 2015 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) (Aptose or the Company), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported that the Food and Drug Administration (FDA), following a voluntary suspension of dosing by the Company and discussions with the Company, placed the Phase Ib clinical trial of APTO-253 in patients with hematologic cancers on clinical hold (Filing, 6-K, Aptose Biosciences, NOV 20, 2015, View Source [SID:1234508301]). This hold is intended to ensure patient safety on the trial and to ensure manufacturing and dosing procedures are consistent with the appropriate documented quality standards.

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The voluntary suspension of dosing by the Company was initiated as a result of a planned preliminary review, which was accelerated to evaluate manufacturing processes and procedures upon the report of an operational difficulty with an IV infusion pump at a clinical site. The pump experienced back pressure during IV patient dosing at the point of the filter. Further review discovered preliminary concerns regarding the documentation records of the manufacturing procedures of the drug product associated with APTO-253.

The Company stated that a complete safety review of all patient files had been completed prior to initial discovery of the manufacturing documentation irregularities, and there have been no drug-related serious adverse events (SAEs) reported. The observed pharmacokinetic levels in the patients treated were within the expected range.

"We are disappointed by these events and have engaged an independent third party review. Importantly, this finding does not undermine the positive safety profile that APTO-253 has demonstrated in clinical development, and we remain confident in its potential as a promising therapeutic option for patients with acute myeloid leukemia and other hematologic malignancies," said William G. Rice, Ph.D., Chairman, President and CEO. "While we expect some delay in the clinical trial, we are committed to ensuring that upon re-initiation of clinical dosing the drug product is of the highest standards. We plan to provide updated timeline guidance as soon as practical."

Key Points:

An internal review identified potential documentation irregularities and the Company voluntarily and immediately suspended dosing of patients out of an abundance of caution to ensure safety.

Aptose currently possesses a sufficient supply of API to create fresh batches of drug product for the resumption of clinical dosing upon FDA approval and guidance.

New contract manufacture organizations have been identified to manufacture fresh batches of cGMP clinical supply upon completion of investigation and in coordination with FDA guidance.

Overall effect to the Phase Ib trial timeline is expected to be partially mitigated by initiation of the new trial sites and updated timeline will be reported as soon as determined.

On November 18, 2015 Sandoz, a Novartis company and the global leader in biosimilars, reported that the US Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) under the 351 (k) pathway for its proposed biosimilar to Amgen’s US-licensed Neulasta (pegfilgrastim)* – a recombinant human granulocyte colony-stimulating factor (G-CSF) (Press release, Sandoz, NOV 20, 2015, View Source [SID:1234508299]).

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Sandoz is seeking approval for the same indication as the reference product. Pegfilgrastim is a prescription medicine used to help reduce the chance of infection due to a low white blood cell count, in patients with cancer (non-myeloid) who receive chemotherapy that can cause fever and a low blood cell count (febrile neutropenia).In the US, the incidence of febrile neutropenia is estimated to be more than 60,000 a year, accounting for nearly eight cases per 1,000 cancer patients.1 Approximately 1.6 million people per year in the US develop non-myeloid cancer.2"

The FDA’s acceptance of our regulatory submission for biosimilar pegfilgrastim – our third biosimilar filed in the US – demonstrates our commitment to expanding patient access to biologics in the US" said Mark McCamish, M.D., Ph.D., and Head of Global Biopharmaceutical & Oncology Injectables Development at Sandoz. "If approved, physicians will have another high-quality Sandoz treatment option for patients needing granulocyte colony-stimulating factors" McCamish continued.

Sandoz believes that the totality of evidence in its submission, including three pivotal clinical trials – one pharmacokinetic and pharmacodynamic study in healthy volunteers and two comparative efficacy and safety studies in breast cancer patients – will demonstrate that the proposed biosimilar is highly similar to the reference product and therefore justifies use of biosimilar pegfilgrastim in the reference product’s indication.

Sandoz has an unwavering commitment to increasing patient access to high-quality, life-enhancing biosimilars. It is the pioneer and global market leader and currently markets three biosimilars. On 3 September, 2015 Sandoz launched the first biosimilar in the United States and recently had its regulatory submission for proposed biosimilar etanercept accepted by the FDA. Sandoz has a leading pipeline with several biosimilars across the various stages of development including five programs in Phase III clinical trials or registration preparation. The company plans to make ten planned regulatory filings over the next three years. As part of the Novartis Group, Sandoz is well-positioned to lead the biosimilars industry based on its experience and capabilities in development, manufacturing and commercialization.