On September 23, 2015 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) reported its plan to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) following a productive pre-NDA meeting for pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R (Press release, CTI BioPharma, SEP 23, 2015, View Source [SID:1234507526]).

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The company expects to submit the NDA in the fourth quarter of 2015 and to request accelerated approval for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/uL). The NDA will be based primarily on data from the PERSIST-1 Phase 3 trial – as well as data from Phase 1 and 2 studies of pacritinib – and additional information requested by the FDA, including a separate study report and datasets for the specific patient population with low platelet counts of less than 50,000 per microliter (<50,000/uL) for whom there are no approved drugs. Submission of an NDA after a single Phase 3 trial under accelerated approval, instead of waiting to complete two Phase 3 trials, could potentially reduce time to market by up to 14 months.

Myelofibrosis is a rare and serious chronic blood cancer that can affect patients of all ages with a median age of 65 years, with an estimated prevalence in the United States of approximately 18,000 patients.

"This improved timing on the plan to submit an NDA – which is supported by data after completion of the PERSIST-1 trial – will allow us the potential for making pacritinib available to patients with low platelet counts earlier than expected," said James A. Bianco, M.D., President and CEO of CTI BioPharma. "We look forward to working with the FDA on the submission and review of this application."

PERSIST Update

Pacritinib is currently being evaluated in two Phase 3 clinical trials, known as the PERSIST program, for patients with myelofibrosis. PERSIST-1 is a randomized, open-label, multicenter Phase 3 trial comparing the efficacy and safety of pacritinib with that of best available therapy (exclusive of a JAK inhibitor) in 327 enrolled patients with myelofibrosis (primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis), regardless of the patients’ platelet counts. PERSIST-2 is a randomized, open-label, multicenter Phase 3 clinical trial evaluating pacritinib compared to best available therapy (BAT), including the approved JAK1/JAK2 inhibitor dosed according to product label for patients with myelofibrosis whose platelet counts are less than or equal to 100,000 per microliter. In October 2013, CTI BioPharma reached agreement with the FDA on a Special Protocol Assessment (SPA) for the PERSIST-2 trial. The SPA is a written agreement between CTI BioPharma and the FDA regarding the design, endpoints and planned statistical analysis approach of the trial to be used in support of a potential NDA submission. The design of PERSIST-1 and PERSIST-2 allows for patients on the BAT arm to crossover and receive treatment with pacritinib if their disease progresses or after they achieve the 24-week measurement endpoint. Although crossover design of clinical trials may confound evaluation of survival, such designs are frequently used in cancer studies, and the FDA has approved multiple oncology drugs that utilized crossover design in Phase 3 trials. The Independent Data Monitoring Committee (IDMC) for the PERSIST program recommended patients on the best available therapy arm should not crossover to receive pacritinib due to non-statistically significant safety concerns in patients who crossover after 24 weeks, which crossover confounds evaluation of survival. After receiving input from external independent experts and providing the FDA the PERSIST-1 data, IDMC’s recommendation and correspondence, CTI BioPharma and Baxalta notified the FDA of the decision to proceed per protocol. Following a written response in lieu of a Type C meeting with the FDA, CTI BioPharma and Baxalta determined that no modifications to the ongoing trials were required. Enrollment in PERSIST-2, which is designed to enroll up to 300 patients in North America, Europe, Australia, New Zealand and Russia is continuing. Based on current timelines, PERSIST-2 enrollment is expected to be completed in the first quarter of 2016. Additional details on PERSIST-2 are available at www.clinicaltrials.gov or www.PERSISTprogram.com.

About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy, or patients who are intolerant of, or whose symptoms are sub-optimally managed on other JAK2 inhibitor therapy. The FDA’s Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Pacritinib does not have regulatory approval and is not commercially available.

CTI BioPharma and Baxalta (NYSE:BXLT) are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.

On September 23, 2015 OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) reported initial results from the Phase 2 Rainier study evaluating apatorsen in combination with ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) and gemcitabine compared to ABRAXANE and gemcitabine alone in patients with untreated metastatic pancreatic cancer (Press release, OncoGenex Pharmaceuticals, SEP 23, 2015, View Source [SID:1234507520]).

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The addition of apatorsen to ABRAXANE and gemcitabine did not demonstrate a survival benefit compared to ABRAXANE and gemcitabine alone. The study was sponsored and conducted by Sarah Cannon Research Institute (SCRI) and further results will be presented by SCRI at a future medical meeting.

Pancreatic cancer accounts for approximately 338,000 new cases each year worldwide. In the U.S., it continues to be the fourth leading cause of cancer death. Most pancreatic cancer patients will die within the first year of diagnosis, and five-year survival rates are less than 10 percent.

"Over the last decade, very few treatments have been able to demonstrate a survival benefit in this very difficult-to-treat cancer," said Johanna Bendell, MD, Director of the GI Cancer Research Program, SCRI, and a primary investigator on the trial. "We understand the dire need for new treatment options and are thankful to the patients who participated in this trial."

The most common grade 3/4 treatment-related toxicities on the apatorsen arm were anemia, neutropenia and fatigue, also consistent with the chemotherapy regimen side effects. These and other adverse events (AEs) observed on the apatorsen arm were similar to those seen in previous trials, with the exception of an increase in grade 4 or greater AEs and serious AEs in this pancreatic cancer trial. While patients in the apatorsen arm had fewer treatment discontinuations due to progressive disease, more patients discontinued therapy due to AEs.

"While we are disappointed with the Rainier results, we also recognize the challenges associated with developing effective treatments for such a lethal and complex disease. We remain confident in our broader apatorsen program, which includes ongoing Phase 2 clinical trials in lung, prostate and bladder cancers," said Scott Cormack, President and CEO of OncoGenex.

Recent Apatorsen Data

Results from an exploratory analysis of the Phase 2 Borealis-1 trial showed that patients with metastatic bladder cancer with poor prognostic features experienced a reduction in risk of death with the addition of 600 mg apatorsen added to first-line chemotherapy, compared to chemotherapy alone.

About Apatorsen and ORCA

Apatorsen (OGX-427) is a once-weekly intravenous (IV) experimental drug that is designed to inhibit production of heat shock protein 27 (Hsp27) to disable cancer cells’ defenses and overcome treatment resistance. Hsp27 in an intracellular protein that protects cancer cells by helping them survive, leading to resistance and more aggressive cancer phenotypes. Both the potential single-agent activity and synergistic activity of apatorsen with cancer treatments may increase the overall benefit of existing therapies and augment the durability of treatment outcomes, which could lead to increased patient survival. The ORCA (Ongoing Studies Evaluating Treatment Resistance in CAncer) program encompasses clinical trials of apatorsen. For more information on apatorsen and ORCA, please visit www. OncoGenex.com or www.orcatrials.com.

On September 23, 2015 Amgen (NASDAQ:AMGN) and Allergan plc. (NYSE:AGN) reported a Phase 3 study of biosimilar candidate ABP 215 met its primary and secondary endpoints (Press release, Amgen, SEP 23, 2015, View Source [SID:1234507518]). The study evaluated the efficacy and safety of ABP 215 compared with Avastin (bevacizumab) in adult patients with advanced non-squamous non-small cell lung cancer (NSCLC).

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The primary endpoint, an assessment of objective response rates (ORR), was within the prespecified margin for ABP 215 compared to bevacizumab, showing clinical equivalence. Safety and immunogenicity of ABP 215 were comparable to bevacizumab. Secondary endpoint results were consistent with the primary finding and included risk difference of ORR, duration of response and progression-free survival (PFS).

ABP 215 is being developed as a biosimilar to bevacizumab, a recombinant immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to vascular endothelial growth factor (VEGF) and inhibits the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2, thus inhibiting establishment of new blood vessels necessary for the maintenance and growth of solid tumors.

"Amgen is committed to bringing high-quality, reliably supplied medicines to patients and we’re excited to leverage our development and manufacturing capabilities in oncology for our biosimilars. The positive Phase 3 results from ABP 215 study showed clinical equivalence in efficacy, and comparable safety and immunogenicity, to bevacizumab," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Non-small cell lung cancer is the leading cause of cancer death in both men and women in the U.S. and the EU. ABP 215 holds the potential to advance access to treatment options for oncology patients."

"The positive Phase 3 clinical results of ABP 215 mark an important step forward in the development of biosimilar treatment options for patients with advanced non-small cell lung cancer," said David Nicholson, executive vice president and president of Global Research and Development of Allergan. "Allergan is committed to developing biosimilars that provide safe, high-quality and effective therapies in key disease areas for patients."

Amgen and Allergan are collaborating on the development and commercialization of four oncology biosimilars. Amgen has a total of nine biosimilars in development. Allergan is also independently developing biosimilars.

Study Design
This was a randomized, double-blind, active-controlled study (study number 20120265) that evaluated safety and efficacy of ABP 215 compared to bevacizumab in adult patients with advanced non-squamous NSCLC receiving first-line chemotherapy with carboplatin and paclitaxel. There were 642 patients enrolled and randomized (1:1) to receive investigational product (ABP 215 or bevacizumab) at a dose of 15 mg/kg administered as an IV infusion every 3 weeks (Q3W) for up to 6 cycles. Among them, there were 328 patients randomized to the ABP 215 group and 314 patients to the bevacizumab group.

The duration of the treatment included a screening period of up to 4 weeks, followed by up to 6 Q3W treatment cycles and an end of treatment visit 21 days after the last dose of investigational product or study specified chemotherapy. Following the end of treatment visit, patients were followed for disease progression and overall survival (OS) until the end of the clinical study, consent was withdrawn, they were lost to follow-up, death or had proscribed therapy (e.g. commercial bevacizumab, non-study anti-cancer treatment).

Clinical equivalence of the primary endpoint was demonstrated by comparing the confidence interval of the risk ratio in ORR between ABP 215 and bevacizumab to a prespecified margin. Response was determined by independent review based on RECIST criteria.

About Non-Small Cell Lung Cancer
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in both men and women in the U.S. and the European Union (EU). In the U.S., there were an estimated 226,160 new cases and 160,340 deaths due to NSCLC in 2012, and in the EU there were an estimated 265,600 new cases and 236,000 deaths due to NSCLC in 2006.1,2 NSCLC arises from the epithelial cells of the lung of the central bronchi to terminal alveoli. The histological type of NSCLC depends on the cells of origin, most commonly squamous cell carcinoma, large cell carcinoma and adenocarcinoma. Cigarette smoking is the primary risk factor for NSCLC, and other risks include exposure to second hand smoke, family history, radon exposure and exposure to air pollution.3-6

For patients with metastatic (Stage IV) NSCLC or recurrent NSCLC following surgery and adjuvant chemotherapy, treatment usually consists of combination chemotherapy with a platinum-based regimen, such as cisplatin and gemcitabine or carboplatin and paclitaxel, in repeated 3-week cycles for up to 6 cycles. For patients without squamous cell histology or a recent history of hemoptysis, addition of the anti-VEGF antibody bevacizumab to this regimen improves ORR and prolongs PFS.7-9

Based on these and other data, bevacizumab has been approved in the U.S., EU and elsewhere for first-line treatment in patients with advanced or recurrent non-squamous NSCLC in combination with platinum-based chemotherapy.

About ABP 215
ABP 215 is being developed as a biosimilar to bevacizumab, which is approved in specific combinations in the U.S., EU and other regions for the treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC as well as metastatic carcinoma of the colon or rectum; metastatic renal cell carcinoma; and other region-specific indications.