On December 6, 2016 Novartis reported results from its Phase III open-label, randomized, active-controlled, multi-center ASCEND-4 study, which found that patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) treated with first-line Zykadia (ceritinib) had a median progression-free survival (PFS) of 16.6 months (95% confidence interval [CI]: 12.6, 27.2), compared to 8.1 months (95% CI: 5.8, 11.1) in patients treated with standard first-line chemotherapy with maintenance (Press release, Novartis, DEC 6, 2016, View Source [SID1234516971]). This equated to a 45% reduction in the risk of disease progression (hazard ratio [HR] = 0.55, P<0.001)[1]. Results were presented during the Presidential Symposium at the 17th World Conference on Lung Cancer (WCLC), hosted by the International Association for the Study of Lung Cancer (IASLC), in Vienna. These late-breaking results were also featured in an official conference press briefing.

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"These data demonstrate the potential to more than double a patient’s progression-free survival when they take Zykadia as their first ALK inhibitor rather than undergoing treatment with chemotherapy," said lead investigator Dr. Gilberto de Castro Jr., head of Thoracic Oncology and Head and Neck Cancer clinic in the Clinical Oncology Service of the Institute of Cancer of São Paulo (ICESP), in São Paulo, Brazil. "For clinicians, who are constantly working to extend a patient’s response to treatment in the first-line setting, the ASCEND-4 results are very compelling."

Overall survival data, a key secondary endpoint of the study, are immature; however, a positive trend in favor of Zykadia was observed, despite 72.4% of patients in the chemotherapy arm receiving an ALK inhibitor as their first treatment after discontinuing chemotherapy. Pre-specified secondary endpoints demonstrating the efficacy of Zykadia in ALK+ advanced NSCLC patients included overall response rate (ORR), overall intracranial response rate (OIRR), disease control rate (DCR) and duration of response (DoR).

Patients taking Zykadia had an ORR of 72.5% (95% CI: 65.5, 78.7) compared to 26.7% (95% CI: 20.5, 33.7) in patients treated with standard chemotherapy. Further, patients with measurable brain metastases experienced an OIRR of 72.7% (95% CI: 49.8, 89.3, n=22) with Zykadia compared to 27.3% (95% CI: 10.7, 50.2, n=22) with standard chemotherapy. Patients without brain metastases at screening experienced a median PFS of 26.3 months (95% CI: 15.4, 27.7, n=130) with Zykadia compared to 8.3 months (95% CI: 6.0, 13.7, n=125) with standard chemotherapy. Additionally, patients taking Zykadia demonstrated a DCR of 84.7% (95% CI: 78.7, 89.5) and DoR of 23.9 months (95% CI: 16.6, not estimable)[1]. Study results were measured by a blinded independent review committee (BIRC). Patients treated with Zykadia also reported better overall general health status and improvement in lung cancer-specific symptoms compared to patients treated with standard chemotherapy[2].

"The patient response to treatment is high and durable in the first-line setting," said Bruno Strigini, CEO, Novartis Oncology. "Based on these results, Novartis is initiating discussions with regulatory authorities worldwide regarding this potential use of Zykadia to further improve outcomes for patients with ALK+ advanced NSCLC."

The safety profile of Zykadia in the ASCEND-4 study was consistent with the previously known safety profile in patients with ALK+ advanced NSCLC. The most common adverse events (AEs) occurring in more than 50% of Zykadia patients were diarrhea (84.7%), nausea (68.8%), vomiting (66.1%), ALT increase (60.3%) and AST increase (52.9%), which were mostly grade 1 and 2 and managed with dose interruption, dose reduction and concomitant medication. No new or unexpected safety concerns were observed[1].

Novartis also presented an initial investigation of the pharmacokinetic (PK) profile of Zykadia 450 mg or 600 mg taken with a low-fat meal versus Zykadia 750 mg taken after fasting, as currently indicated. This Phase I prospective, open-label, multicenter, randomized study found (in Part 1) that relative to the 750 mg fasted arm, the 450 mg fed arm demonstrated comparable steady-state PK, while the 600 mg fed arm showed approximately 25% higher steady-state PK. Further, preliminary safety data found the overall frequency of AEs were comparable between groups; however, incidences of gastrointestinal-related AEs (diarrhea, nausea or vomiting) were lowest in the Zykadia 450 mg group that ate a low-fat meal, with no grade 3/4 AEs reported[3]. This study is ongoing and continues to enroll treatment-naïve patients into Part 2, assessing efficacy across the three treatment arms and evaluating safety follow-up.

One of 12 known genetic drivers of NSCLC, the ALK gene arrangement affects approximately 2-7% of people with NSCLC[4],[5]. These patients are candidates for treatment with a targeted ALK inhibitor[5]. To determine a personalized treatment plan, medical organizations recommend genetic testing for patients with lung cancer[6].

About ASCEND-4
ASCEND-4 was a Phase III randomized, open-label, multicenter, global clinical trial to evaluate the safety and efficacy of Zykadia compared to standard chemotherapy, including maintenance, in adult patients with Stage IIIB or IV ALK+ advanced NSCLC who received no prior therapy for their advanced disease. Patients received Zykadia orally at 750 mg/daily or standard pemetrexed-based platinum doublet chemotherapy per label (pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5-6) for 4 cycles followed by pemetrexed maintenance.
Of 376 patients, 189 (59 with brain metastases) were randomized to Zykadia and 187 (62 with brain metastases) to chemotherapy. Among patients randomized to the chemotherapy arm, 105 (60%) received an ALK inhibitor as their first treatment after chemotherapy.

About Zykadia
Zykadia is an oral, selective inhibitor of anaplastic lymphoma kinase (ALK), a gene that can fuse with others to form an abnormal "fusion protein" that promotes the development and growth of certain tumors in cancers including non-small cell lung cancer (NSCLC). Zykadia was granted conditional approval in the EU for the treatment of adult patients with ALK-positive advanced NSCLC previously treated with crizotinib. In the US, Zykadia was granted accelerated approval for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib.

Zykadia is currently approved in over 55 countries worldwide. Please visit www.NovartisOncology.com/news/product-portfolio/zykadia for additional information.

Zykadia Important Safety Information
Zykadia may cause serious side effects.

Zykadia may cause stomach upset and intestinal problems in most patients, including diarrhea, nausea, vomiting and stomach-area pain. These problems can be severe. Patients should follow their doctor’s instructions about taking medicines to help these symptoms, and should call their doctor for advice if symptoms are severe or do not go away.

Zykadia may cause severe liver injury. Patients should have blood tests prior to the start of treatment with Zykadia, every two weeks for the first month of treatment and monthly thereafter, and should talk to their doctor right away if they experience any of the following symptoms: tiredness (fatigue), itchy skin, yellowing of the skin or the whites of the eyes, nausea or vomiting, decreased appetite, pain on the right side of the abdomen, urine turns dark or brown, or bleeding or bruising more easily than normal.

Zykadia may cause severe or life-threatening swelling (inflammation) of the lungs during treatment that can lead to death. Symptoms may be similar to those symptoms from lung cancer. Patients should tell their doctor right away about any new or worsening symptoms, including trouble breathing or shortness of breath, fever, cough, with or without mucous, or chest pain.

Zykadia may cause very slow, very fast, or abnormal heartbeats. Doctors should check their patient’s heart during treatment with Zykadia. Patients should tell their doctor right away if they feel new chest pain or discomfort, dizziness or lightheadedness, faint, or have abnormal heartbeats, blue discoloration of lips, shortness of breath, swelling of lower limbs or skin, or if they start to take or have any changes in heart or blood pressure medicines.

Zykadia may cause high levels of glucose in the blood. People who have diabetes or glucose intolerance, or who take a corticosteroid medicine have an increased risk of high blood sugar with Zykadia. Patients should have glucose blood tests prior to the start of treatment with Zykadia and during treatment. Patients should follow their doctor’s instructions about blood sugar monitoring and call their doctor right away with any symptoms of high blood sugar, including increased thirst and/or urinating often.

Zykadia may cause high levels of pancreatic enzymes in the blood and may cause pancreatitis. Patients should have blood tests prior to the start of treatment with Zykadia and as needed during their treatment with Zykadia. Patients should talk to their doctor if they experience signs and symptoms of pancreatitis which including upper abdominal pain that may spread to the back and get worse with eating.

Before patients take Zykadia, they should tell their doctor about all medical conditions, including liver problems; diabetes or high blood sugar; heart problems, including a condition called long QT syndrome; if they are pregnant, if they think they may be pregnant, or if they plan to become pregnant; are breastfeeding or plan to breastfeed.

Zykadia may harm unborn babies. Women who are able to become pregnant must use a highly effective method of birth control (contraception) during treatment with Zykadia and up to 3 months after stopping Zykadia. It is not known if Zykadia passes into breast milk. Patients and their doctor should decide whether to take Zykadia or breastfeed, but should not do both.

Patients should tell their doctor about medicines they take, including prescription medicines, over-the-counter medicines, vitamins and herbal supplements. If they take Zykadia while using oral contraceptives, the oral contraceptives may become ineffective.

The most common adverse reactions with an incidence of >=10% were diarrhea, nausea, vomiting, tiredness (fatigue), liver laboratory test abnormalities (requires blood test monitoring), abdominal pain, decreased appetite, constipation, rash, kidney laboratory test abnormalities (requires blood test monitoring), heartburn and anemia. Grade 3-4 adverse reactions with an incidence of >=5% were liver laboratory test abnormalities, tiredness (fatigue), diarrhea, nausea and hyperglycemia (requires blood test monitoring).

Patients should stop taking Zykadia and seek medical help immediately if they experience any of the following, which may be signs of an allergic reaction:

Difficulty in breathing or swallowing
Swelling of the face, lips, tongue or throat
Severe itching of the skin, with a red rash or raised bumps
Patients should tell their doctor of any side effect that bothers them or does not go away. These are not all of the possible side effects of Zykadia. For more information, patients should ask their doctor or pharmacist.

Patients should take Zykadia exactly as their health care provider tells them. Patients should not change their dose or stop taking Zykadia unless their health care provider advises them to. Zykadia should be taken once a day on an empty stomach. Patients should not eat for at least 2 hours before and 2 hours after taking Zykadia. If a dose of Zykadia is missed, they should take it as soon as they remember. If their next dose is due within the next 12 hours, they should skip the missed dose and take the next dose at their regular time. They should not take a double dose to make up for a forgotten dose. Patients should not drink grapefruit juice or eat grapefruit during treatment with Zykadia, as it may make the amount of Zykadia in their blood increase to a harmful level. If patients have to vomit after swallowing Zykadia capsules, they should not take more capsules until their next scheduled dose.

Please see full Prescribing Information for Zykadia.

On December 6, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported the presentation of SL-401 lead-in data from its ongoing Phase 2 trial in acute myeloid leukemia (AML) in remission with minimal residual disease (MRD) and ongoing Phase 2 trial in high-risk myeloproliferative neoplasms (MPN) at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Stemline Therapeutics, DEC 6, 2016, View Source [SID1234516963]). The AML/MRD results were delivered via oral presentation by Andrew A. Lane, M.D., Ph.D., from the Dana-Farber Cancer Institute (Boston, MA) and the MPN results were presented by Mrinal S. Patnaik, M.D. from the Mayo Clinic (Rochester, MN).

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The full presentations are available on the Stemline website, under the "Scientific Presentations" tab (see: View Source).

Safety Overview

SL-401 was found to be safe and well tolerated, and side effects were predictable and manageable. The lead-in dose escalation stages of both Phase 2 studies (3 x 3 design) were completed without dose limiting toxicity (DLT) and a maximum tolerated dose (MTD) was not reached in either study (n=9 patients in AML/MRD lead-in; n=9 patients in MPN lead-in). 12 ug/kg/day was the highest tested dose in both studies and is currently the dose level being used in the expansion stage of both studies.
Efficacy Overview

AML/MRD – Early signs of efficacy in the AML study included an MRD+ AML patient who sustained a decrease in MRD, determined locally, treated at 12 ug/kg/day who then went on to stem cell transplant. The expansion stage is currently enrolling and, for uniformity, will utilize a central facility for MRD analysis.

MPN – Early signs of efficacy in the MPN study including a patient with chronic myelomonocytic leukemia (CMML) who sustained a bone marrow complete response (BMCR) and reduction in spleen size. The expansion stage is currently enrolling CMML as well as additional MPN types including myelofibrosis, mastocytosis, and primary eosinophilic disorder.
Andrew A. Lane, M.D., Ph.D., lead author on the AML study, commented, "Given the unacceptably high relapse rates seen in AML, MRD has emerged as an important predictor of relapse with CD123 as a key target for therapy. The preliminary results seen with SL-401 in this setting are promising. We look forward to enrolling patients in the expansion stage of the trial as we continue to optimize and refine methods to assess and follow MRD."

Mrinal S. Patnaik, M.D., lead author on the MPN study, noted, "The early data from the dose escalation portion of the trial suggests SL-401 can be dosed safely in this patient population. Additionally, we are observing encouraging signs of clinical activity in several patients. We look forward to enrolling patients in the expansion stage of the trial."

On December 6, 2016 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology reported the presentation of data from a case match control analysis of the PROPEL Study in a poster presentation session at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Spectrum Pharmaceuticals, DEC 6, 2016, View Source [SID1234516962]).

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Abstract #4149: Case Match Control Analysis of Propel Reveals Survival Advantage for Patients with Relapsed/Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL) Treated with Pralatrexate

In this retrospective, observational study, 80 patients out of 109 treated on the PROPEL study were successfully matched 1:1 with the control population. A highly significant difference in the Overall Survival between the control population and the pralatrexate group was observed. The overall survival observed in the control population was 4.04 months (95% CI 2.60, 6.01) which was consistent with historical controls, while the median OS in for pralatrexate treated cohort was 14.78 months (95% CI 10.61-22.31). The most common adverse reactions from the PROPEL study were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events were pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia. See below for Important Safety Information.

"In this case match controlled study, the overall survival observed in the pralatrexate group was over three-fold higher than a case matched control group," said Owen A. O’Connor, MD, PhD, Director of the Center for Lymphoid Malignancies, Professor of Medicine and Experimental Therapeutics at Columbia Medical Center, New York Presbyterian Medical Center. "The PROPEL study, which was a Phase 2, open-label, single-arm, multi-center, international trial, included patients that were heavily pretreated, with a median of three prior systemic therapies (ranging between 1 and 12). This is one of the first times a case match control analysis has been used to understand the impact of a drug on the outcome of a rare disease, like PTCL. Importantly, we believe this may be a valuable paradigm that can be used in other orphan diseases in cancer medicine."

"We are honored to present this important data at the 58th ASH (Free ASH Whitepaper) Meeting," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "We are encouraged to see positive data continuing to emerge from the PROPEL study that was the basis for FOLOTYN’s approval. FOLOTYN was the first drug approved for the treatment of relapsed or refractory PTCL and continues to have the leading market share in 2nd line therapy. PTCL is an aggressive disease with a poor prognosis and we are excited that FOLOTYN has the potential to improve outcome for PTCL patients. We are also looking forward to emerging new data in combination treatments that might prove to benefit PTCL patients in earlier lines of treatment and with the possibility to include FOLOTYN in future PTCL first line regimens."

About Spectrum Pharmaceuticals, Inc.

Spectrum Pharmaceuticals is a leading biotechnology company focused on acquiring, developing, and commercializing drug products, with a primary focus in Hematology and Oncology. Spectrum currently markets six hematology/oncology drugs, and has an advanced stage pipeline that has the potential to transform the Company. Spectrum’s strong track record for in-licensing and acquiring differentiated drugs, and expertise in clinical development have generated a robust, diversified, and growing pipeline of product candidates in advanced-stage Phase 2 and Phase 3 studies. More information on Spectrum is available at www.sppirx.com.

About FOLOTYN

FOLOTYN, (pralatrexate injection), a folate analogue metabolic inhibitor, was discovered by Memorial Sloan-Kettering Cancer Center, SRI International and Southern Research Institute and developed by Allos Therapeutics. In September 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval for FOLOTYN for use as a single agent for the treatment of patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression-free survival or overall survival has not been demonstrated. FOLOTYN has been available to patients in the U.S. since October 2009. An updated analysis of data from PROPEL, the pivotal study of FOLOTYN in patients with relapsed or refractory PTCL, was published in the March 20, 2011 issue of the Journal of Clinical Oncology. FOLOTYN has patent protection through July 2022, based on a five-year patent term extension through the Hatch-Waxman Act.

Important FOLOTYN Safety Information

Warnings and Precautions

FOLOTYN may suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anemia. Monitor blood counts and omit or modify dose for hematologic toxicities.

Mucositis may occur. If greater-than or equal to Grade 2 mucositis is observed, omit or modify dose. Patients should be instructed to take folic acid and receive vitamin B12 to potentially reduce treatment-related hematological toxicity and mucositis.

Fatal dermatologic reactions may occur. Dermatologic reactions may be progressive and increase in severity with further treatment. Patients with dermatologic reactions should be monitored closely, and if severe, FOLOTYN should be withheld or discontinued. Tumor lysis syndrome may occur. Monitor patients and treat if needed.

FOLOTYN can cause fetal harm. Women should avoid becoming pregnant while being treated with FOLOTYN and pregnant women should be informed of the potential harm to the fetus.

Use caution and monitor patients when administering FOLOTYN to patients with moderate to severe renal function impairment.

Elevated liver function test abnormalities may occur and require monitoring. If liver function test abnormalities are greater-than or equal to Grade 3, omit or modify dose.

Adverse Reactions

The most common adverse reactions were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events are pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia.

Use in Specific Patient Population

Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.

Drug Interactions

Co-administration of drugs subject to renal clearance (e.g., probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal clearance.

Please see FOLOTYN Full Prescribing Information at www.FOLOTYN.com.

On December 6, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported the initiation of a Managed Access Program for PB272 (neratinib) (Press release, Puma Biotechnology, DEC 6, 2016, View Source [SID1234516961]). Managed access programs provide physicians and patients access to medicines when there are limited or no other therapeutic options available.

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Puma’s Managed Access Program for neratinib will enable participation from countries outside the United States, including European Union Member States, where permitted by applicable rules, procedures and regulatory authorities. The program will provide access to neratinib for the treatment of early stage HER2-positive breast cancer (extended adjuvant setting), HER2-positive metastatic breast cancer and HER2-mutated solid tumors. Patients must not be able to participate in any ongoing neratinib clinical trial to qualify for Puma’s managed access program. Patients in the managed access program will be given neratinib and will be instructed to take a prophylaxis during treatment to manage neratinib-related diarrhea, which the Company expects will consist of high dose loperamide and budesonide.

Puma Biotechnology has partnered with Caligor Opco LLC, which specializes in early access to medicines, to implement and oversee the Managed Access Program for neratinib.

"The guiding principle behind our Managed Access Program is to provide neratinib — through physician-requested access — to patients with significant unmet medical needs as soon as practical, in a manner that is safe, ethical, compliant and effective," said Alan H. Auerbach, Chief Executive Officer and President of Puma. "With Caligor managing the day-to-day operations of the program, we can direct our efforts toward our regulatory filings and implementing our plans for commercialization."

Questions or inquiries regarding the Neratinib Managed Access Program should be directed to [email protected].

About Caligor

Caligor Opco LLC, a portfolio company of Diversis Capital, LLC, is a global company that manages the regulatory, logistics and supply chain needs for global access programs as well as the sourcing, storing and distribution of comparator drugs for clinical trials. Caligor’s global access programs help to meet the medical needs of patients worldwide by providing access to unlicensed / unapproved medicines in situations where the drug has not yet been approved, or is otherwise commercially unavailable. In addition, through its proprietary TrialAssist program, Caligor optimizes its services by providing for labeling, QP certification, storage, distribution and destruction of clinical trial and unlicensed medicines managed in the access programs. The Company serves pharmaceutical and biotechnology companies from facilities in Secaucus, New Jersey, and Dartford, UK, as well as strategically situated depot locations worldwide. More information is available at View Source

On December 6, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer and Cellworks, a customized therapy design company that improves clinical outcomes and creates value for pharma, payers and physicians, reported the presentation of their collaborative effort to identify higher-risk MDS (HR-MDS) patients that are likely to respond to rigosertib at the 2016 ASH (Free ASH Whitepaper) Annual Meeting in San Diego California, taking place December 3-6, 2016 (Press release, Onconova, DEC 6, 2016, View Source [SID1234516960]).

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The presentation by Dr. Guillermo Garcia-Manero from the MD Anderson Cancer Center, lead investigator from the ONTME trial, used Cellworks’ proprietary bio-simulation platform to retrospectively correlate clinical benefit to IV rigosertib treatment in the Phase 3 ONTIME study in HR-MDS patients with molecular and cytogenetic data. This computer simulation led to the characterization of certain biological pathways that predict response to IV rigosertib in HR-MDS patients. Notably, patients with these predictive biological pathways also shared common cytogenetic abnormalities — trisomy of chromosomes 8 and 21 — that correlated with positive clinical outcome in ONTIME.

"This retrospective analysis of ONTIME has helped identify biological factors related to clinical outcomes to treatment with IV rigosertib," stated Guillermo Garcia-Manero, MD, Chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center, and lead author of the study. "These results confirm prior studies where patients with certain cytogenetic abnormalities were sensitive to IV rigosertib. These data also reinforce the clinical strategy of the ongoing Phase 3 INSPIRE trial to target only the highest-risk MDS patients with rigosertib."

"We are excited by this use of our proprietary bio-simulation platform to predict response to novel therapeutics in a heterogeneous disease like HR-MDS," commented Yatin Mundkur, CEO of Cellworks. "Among other applications, the Cellworks platform is intended to inform the design of Phase 2 and 3 clinical trials by establishing and validating inclusion criteria. In this case, we are pleased that this analysis has validated enrollment criteria for Onconova’s Phase 3 INSPIRE trial."

The poster entitled "Computational Analysis of Genomic Abnormalities from a Phase 3 Trial of Rigosertib in Higher-Risk MDS: Simulation of a Predictive Signature for Clinical Response," was presented on December 5, 2016 at the ASH (Free ASH Whitepaper) Annual Meeting in San Diego, California. A copy of the poster is available by visiting the Scientific Presentations section under the Investors & Media tab of Onconova’s website.

About Onconova Therapeutics, Inc.

Onconova Therapeutics is a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer. Onconova’s clinical and pre-clinical stage drug development candidates are derived from its extensive chemical library and are designed to work against specific cellular pathways that are important in cancer cells, while causing minimal damage to normal cells. The Company’s most advanced product candidate, rigosertib, is a small molecule inhibitor of cellular signaling and acts as a RAS mimetic. These effects of rigosertib appear to be mediated by direct binding of the compound to the RAS-binding domain (RBD) found in many RAS effector proteins, including the Raf and PI3 kinases. Rigosertib is protected by issued patents (earliest expiry in 2026) and has been awarded Orphan Designation for MDS in the United States, Europe and Japan. In addition to rigosertib, two other candidates are in the clinical stage, and several candidates are in pre-clinical stages. For more information, please visit View Source

About IV Rigosertib

The intravenous form of rigosertib has been employed in Phase 1, 2, and 3 clinical trial involving more than 800 patients, and is currently being evaluated in the randomized Phase 3 global INSPIRE trial as 2nd-line treatment for patients with higher-risk MDS, after failure of hypomethylating agent, or HMA, therapy. This formulation is suited for patients with advanced disease and provides long duration of exposure and ensures adequate dosing under a controlled setting.

About INSPIRE

The INternational Study of Phase III IV RigosErtib, or INSPIRE, is based on guidance received from the U.S. Food and Drug Administration and European Medicines Agency and derives from the findings of the ONTIME Phase 3 trial. INSPIRE is a multi-center, randomized controlled study to assess the efficacy and safety of IV rigosertib in HR-MDS patients who had progressed on, failed to respond to, or relapsed after previous treatment with an HMA within the first nine months of initiation of HMA treatment. This time frame optimizes the opportunity to respond to treatment with an HMA prior to declaring treatment failure, as per NCCN Guidelines. The trial will enroll approximately 225 patients randomized at a 2:1 ratio into two treatment arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. The primary endpoint of INSPIRE is overall survival and an interim analysis is anticipated. Full details of the INSPIRE trial, such as inclusion and exclusion criteria, as well as secondary endpoints, can be found on clinicaltrials.gov (NCT02562443).