On September 1, 2017 Pfizer Inc. (NYSE:PFE) reported that the U.S. Food and Drug Administration approved MYLOTARG (gemtuzumab ozogamicin) for adults with newly diagnosed CD33-positive acute myeloid leukemia (AML), and adults and children 2 years and older with relapsed or refractory CD33-positive AML (Press release, Pfizer, SEP 1, 2017, View Source [SID1234520362]).1 MYLOTARG is the first therapy with an indication that includes pediatric AML. It is also the only AML therapy that targets CD33, an antigen expressed on AML cells in up to 90% of patients.

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"The FDA approval of MYLOTARG fills a critical unmet need for many adults and children with AML, which can be fatal in a matter of months or even weeks if not treated and has a high relapse rate," said Liz Barrett, global president, Pfizer Oncology. "Based on clinical data, real-world experience and support from the AML community, we are grateful MYLOTARG now has the potential to help a broad range of AML patients."

MYLOTARG was originally approved in 2000 at a higher dose under the FDA’s accelerated approval program for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years or older and who were not considered candidates for other cytotoxic chemotherapy. In 2010, Pfizer voluntarily withdrew MYLOTARG in the U.S. after a confirmatory trial failed to show clinical benefit and there was a higher rate of fatal toxicity compared to chemotherapy. MYLOTARG has remained on the market in Japan and has been available to individual patients through Pfizer’s compassionate use programs. Due to the critical unmet need for patients with AML, there remained great interest among AML clinicians to evaluate MYLOTARG using different doses and different schedules. These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of MYLOTARG.

"Today is an important day for patients, their families and the entire AML community, as the approval of MYLOTARG brings forth a long-awaited treatment option that may lead to deeper, more durable remissions for patients with AML," said Jorge Cortes, MD, University of Texas, MD Anderson Cancer Center. "After many years, we are finally seeing progress in the treatment of AML, which has renewed my hope in improving outcomes for my patients. I am pleased that I can now offer many adult and pediatric patients targeted treatment with MYLOTARG."

Today’s approval of MYLOTARG is based on several investigator-led clinical trials, including ALFA-0701, AML-19 and MyloFrance-1.1

The ALFA-0701 trial was a Phase 3, multicenter, randomized, open-label study of 271 patients with newly-diagnosed de novo AML, using a new, lower fractionated dose of MYLOTARG. Patients received MYLOTARG 3 mg/m2 on days 1, 4 and 7 in combination with conventional chemotherapy or chemotherapy alone. The primary endpoint was event-free survival (EFS). Administering MYLOTARG (n=135) in addition to standard induction chemotherapy resulted in a significant improvement in EFS compared with chemotherapy alone (n=136) in patients with newly diagnosed AML. Event-free survival was 17.3 months for patients receiving MYLOTARG compared with 9.5 months for those receiving chemotherapy alone (HR = 0.56 [95% CI: (0.42, 0.76)]).1

Study AML-19 was a multicenter, randomized, open-label Phase 3 study comparing single agent MYLOTARG (n=118) to best supportive care (n=119) for elderly patients who could not tolerate other AML therapies. As initial treatment, patients received MYLOTARG 6 mg/m2 on day 1 and MYLOTARG 3 mg/m2 on day 8. As continued treatment, patients without evidence of disease progression received MYLOTARG 2 mg/m2 on day 1 every 4 weeks. The efficacy of MYLOTARG was established on the basis of a significant improvement in overall survival (OS). Median OS was 4.9 months for patients receiving MYLOTARG compared with 3.6 months for patients receiving best supportive care (HR=0.69 [95% CI: 0.53-0.90] [2-sided p=0.005]).1

MyloFrance-1 was a Phase 2, single-arm, open-label study of 57 adult patients in first relapse. Patients received single agent MYLOTARG 3mg/m2 on days 1, 4 and 7. The efficacy of MYLOTARG was established on the basis of complete remission (CR) rate and duration of remission. In the trial, 15 (26%; 95% CI: 16%-40%) patients achieved a complete remission (CR) and median relapse-free survival (RFS) was 11.6 months.1

The U.S. labeling for MYLOTARG includes a boxed warning for hepatotoxicity, including severe or fatal hepatic veno-occlusive disease (VOD). Veno-occlusive disease has been reported in association with the use of MYLOTARG as a single agent and as part of a combination chemotherapy regimen (5%). In patients who received MYLOTARG, the most common (≥15%) adverse reactions were hemorrhage, infection, fever, nausea, vomiting, constipation, headache, increased ALT, increased AST, rash and mucositis.

Pfizer is committed to helping patients gain access to Pfizer medicines, including MYLOTARG, and related educational tools, resources and services, regardless of their financial or health insurance status through the company’s patient assistance programs. Patients can visit www.MYLOTARG.com or call 1-877-744-5675 to learn more.

The full prescribing information, including BOXED WARNING, for MYLOTARG can be found here: View Source

IMPORTANT MYLOTARG (gemtuzumab ozogamicin) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

WARNING: Hepatotoxicity, including severe or fatal hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), has been reported in association with the use of MYLOTARG as a single agent, and as part of a combination chemotherapy regimen. Monitor frequently for signs and symptoms of VOD after treatment with MYLOTARG.

Hepatotoxicity, Including Veno-occlusive Liver Disease (VOD): An increased risk of VOD was observed in patients with moderate/severe hepatic impairment and patients who received MYLOTARG either before or after HSCT. Assess ALT, AST, total bilirubin, and alkaline phosphatase prior to each dose of MYLOTARG. After treatment with MYLOTARG, monitor frequently for signs and symptoms of VOD; these may include elevations in ALT, AST, and total bilirubin, hepatomegaly, rapid weight gain, and ascites. Monitoring only total bilirubin may not identify all patients at risk of VOD. For patients who develop abnormal liver tests, more frequent monitoring of liver tests and clinical signs and symptoms of hepatotoxicity is recommended. For patients who proceed to HSCT, monitor liver tests frequently during the post-HSCT period, as appropriate. Manage signs or symptoms of hepatic toxicity by dose interruption or discontinuation of MYLOTARG. In patients who experience VOD, discontinue MYLOTARG and treat according to standard medical practice.

Infusion-Related Reactions (Including Anaphylaxis): Life-threatening or fatal infusion-related reactions can occur during or within 24 hours following infusion of MYLOTARG. Signs and symptoms of infusion-related reactions may include fever, chills, hypotension, tachycardia, hypoxia, and respiratory failure. Premedicate prior to MYLOTARG infusion. Monitor vital signs frequently during infusion. Interrupt infusion immediately for patients who develop evidence of infusion reaction, especially dyspnea, bronchospasm, or hypotension. Monitor patients during and for at least 1 hour after the end of the infusion or until signs and symptoms completely resolve. Discontinue use of MYLOTARG in patients who develop signs or symptoms of anaphylaxis, including severe respiratory symptoms or clinically significant hypotension.

Hemorrhage: MYLOTARG is myelosuppressive and can cause fatal or life-threatening hemorrhage due to prolonged thrombocytopenia. Assess blood counts prior to each dose of MYLOTARG and monitor blood counts frequently after treatment with MYLOTARG until resolution of cytopenias. Monitor patients for signs and symptoms of bleeding during treatment with MYLOTARG. Manage severe bleeding, hemorrhage, or persistent thrombocytopenia using dose delay or permanent discontinuation of MYLOTARG, and provide supportive care per standard practice.

QT Interval Prolongation: QT interval prolongation has been observed in patients treated with other drugs containing calicheamicin. When administering MYLOTARG to patients who have a history of or predisposition for QTc prolongation, who are taking medicinal products that are known to prolong QT interval, and in patients with electrolyte disturbances, obtain electrocardiograms and electrolytes prior to the start of treatment and as needed during administration.

Adverse Cytogenetics: In a subgroup analysis in ALFA-0701, the addition of MYLOTARG to standard combination chemotherapy did not improve event-free survival in the subgroup of patients having adverse-risk cytogenetics. For patients being treated with MYLOTARG in combination with daunorubicin and cytarabine for newly diagnosed de novo AML, when cytogenetics testing results become available consider whether the potential benefit of continuing treatment with MYLOTARG outweighs the risks for the individual patient.

Embryo-Fetal Toxicity: MYLOTARG can cause embryo-fetal harm when administered to a pregnant woman. Advise patients of reproductive potential to use effective contraception during and for 3 and 6 months following treatment for males and females, respectively. Apprise pregnant women of the potential risk to the fetus. Advise women to contact their healthcare provider if they become pregnant or if pregnancy is suspected during treatment with MYLOTARG.

Adverse Reactions: The most common adverse reactions (greater than 15%) were hemorrhage, infection, fever, nausea, vomiting, constipation, headache, increased AST, increased ALT, rash, and mucositis.

Contraindications: Hypersensitivity to MYLOTARG or any of its components. Reactions have included anaphylaxis.

The full prescribing information, including BOXED WARNING, for MYLOTARG can be found here: View Source.

About AML

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and accounts for approximately 80% of all cases of acute leukemia.2 About 21,380 people are expected to be diagnosed with AML in the United States in 2017.3 The majority of AML cases occur in adults, but about 500 children are diagnosed with AML each year.4 Acute myeloid leukemia is the second most common leukemia in children.6 The majority of children (85%) will achieve a response after initial treatment, with approximately 5% being refractory to treatment.5 Additionally, approximately 30% of children will have their disease return5. Only one in four patients with AML survive longer than five years.4

About MYLOTARG (gemtuzumab ozogamicin)

MYLOTARG is an antibody-drug conjugate (ADC) composed of the cytotoxic agent calicheamicin, attached to a monoclonal antibody (mAB) targeting CD33, an antigen expressed on the surface of myeloblasts in up to 90 percent of AML patients.6,7,8 When MYLOTARG binds to the CD33 antigen on the cell surface it is absorbed into the cell and calicheamicin is released causing cell death.1,7,8

MYLOTARG is commercially available in Japan where it is approved for the treatment of patients with relapsed or refractory CD33-positive AML who are not considered candidates for other cytotoxic chemotherapy.

MYLOTARG originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development and commercialization activities for this molecule.

On September 1, 2017 ONCURIOUS NV, a Belgium-based biotech company focusing on the development of innovative oncology treatments, reported that it has reached principle agreement with VIB to acquire exclusive licences to a portfolio of five unique next generation immuno-oncology assets, based on seminal work originating from the VIB-KULeuven labs of Massimiliano Mazzone and Gabriele Bergers, and from the VIB-VUB lab of Jo Van Ginderachter (Press release, Oncurious, SEP 1, 2017, View Source [SID1234520363]).

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Oncurious broadens its ongoing clinical development activities in orphan pediatric oncology indications with preclinical research and drug development programs, resulting in an exciting pipeline of next-generation immuno-oncology drugs targeting a broad spectrum of cancers.

VIB Discovery Sciences will take the lead in the pre-clinical development of these new projects. As part of this agreement, VIB will increase its stake in Oncurious, with ThromboGenics remaining the majority shareholder. VIB will also receive a royalty on future sales of any of these assets. ThromboGenics invests an additional €2.1 million in Oncurious.

Dr Johan Cardoen, Managing Director of VIB comments, "VIB has been developing a portfolio of next-generation immuno-oncology assets. As there are a lot of synergies within that portfolio, we also see the opportunity to develop all assets within one company. As a venture partner of Oncurious, we are looking forward to take the company to the next level."

Patrik De Haes, MD, Executive Chairman of ONCURIOUS NV comments, "This new collaboration with VIB and the resulting portfolio propels Oncurious into the very exciting area of immuno-oncology, with a focus on next generation therapies. We are very privileged to have the world-class VIB-team as our venture partner."

Oncurious is currently conducting a Phase I/IIa clinical trial for the evaluation of TB-403 in the treatment of medulloblastoma, in collaboration with BioInvent. TB-403 is a humanized monoclonal antibody against placental growth factor (PLGF). PLGF is expressed in several types of cancer, including medulloblastoma.

On September 1, 2017 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that updated data from the ongoing Phase 1b trial of FP-1039/GSK3052230 (hereafter FP-1039) in mesothelioma patients were reported today in an abstract submitted to the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress to be held Sept. 8 – 12, 2017, in Madrid, Spain (Press release, Five Prime Therapeutics, SEP 1, 2017, View Source [SID1234520361]). The abstract titled "Multicenter, Nonrandomized, Open-Label Phase 1b Study of FP-1039/GSK3052230 with Chemotherapy: Results in Malignant Pleural Mesothelioma (MPM)" by Dr. Jose Trigo et al. is available at View Source

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The MPM arm of the study evaluated the safety and efficacy of FP-1039 (IV weekly) in combination with standard pemetrexed + cisplatin. The study design involved dose escalation until maximum tolerated dose (MTD) followed by a cohort expansion phase. Endpoints included safety, overall response rate by modified RECIST 1.1, disease control rate (DCR), progression free survival (PFS) and exploratory translational objectives.

As of the cutoff date of March 17, 2017, 36 patients were dosed at 10, 15 and 20 mg/kg doses of FP-1039. Three DLTs were observed at 20 mg/kg but none occurred at 15 mg/kg; therefore, MTD was declared at this dose.

Safety Data

The most common adverse events (AEs; all grades) observed were: nausea (56%) decreased appetite (36%), fatigue (33%) and infusion reaction (33%).
Efficacy Data

The confirmed objective response rate (ORR) of all evaluable patients at or below the MTD was 48%, with 13 partial responses in 27 patients.

The disease control rate (DCR) was 100%.

The median PFS was 7.4 months.
As of May 8, 2017, six patients stayed on the study for over 1 year, of which three were still ongoing.

About FP-1039

FP-1039 is a protein drug designed to intervene in FGF signaling. As a ligand trap, FP-1039 binds to FGF ligands circulating in the extracellular space (such as FGF2), preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells. Treatment with FP-1039 has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF-23. GlaxoSmithKline (GSK) was the sponsor of the trial.

On September 1, 2017 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, reported financial results for the six months ended June 30, 2017 and provided clinical and corporate updates (Press release, Can-Fite BioPharma, SEP 1, 2017, View Source [SID1234520359]).

Clinical Development Program and Corporate Highlights Include:

Namodenoson (CF102): Progress in Clinical Development and Receipt of Milestone Payment

● Patient Enrollment Completed in Phase II Liver Cancer Trial of Namodenoson

Can-Fite enrolled and randomized all 78 patients for its global Phase II study of Namodenoson in the treatment of hepatocellular carcinoma (HCC), the most common form of liver cancer. Patients with advanced HCC, Child Pugh B, were enrolled in the U.S., Europe and Israel. The primary endpoint of the Phase II study is overall survival. Can-Fite is following the survival data closely and plans to perform the survival analysis at the earliest possible opportunity. The HCC market is expected to generate $1.4 billion in sales in 2019.

● Milestone Payment Received for Distribution of Namodenoson in Korea for the Treatment of Liver Cancer

In August 2017, Can-Fite received a milestone payment of $500,000 from Chong Kun Dang Pharmaceuticals (CKD), which licensed the exclusive right to distribute Namodenoson for the treatment of liver cancer in Korea upon receipt of regulatory approvals. The payment is part of a deal worth up to $3,000,000 in upfront and milestone payments plus 23% royalties.

● Namodenoson to Commence Phase II Trial in the Treatment of NAFLD/NASH

During the second quarter of 2017, Can-Fite conducted a successful Clinical Investigator Meeting with principal investigators, researchers, and doctors participating as clinical investigators in the Company’s Phase II trial of Namodenoson in the treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Namodenoson drug supply for the trial has been paid for and is ready to be administered to patients. The trial protocol has been approved by two leading Institutional Review Boards in Israel. Can-Fite estimates the cost of this Phase II trial to be less than $1 million. Patient enrollment is expected to begin in the third quarter of 2017. By 2025, the addressable pharmaceutical market for NASH is estimated to reach $35-40 billion.

● Established Clinical Advisory Board for NASH Indication

Can-Fite established a Clinical Advisory Board comprised of Key Opinion Leaders to provide advice and steer Namodenoson’s clinical development program in the treatment of NAFLD and NASH. Board members include researchers and medical practitioners in the field of liver disease from institutions including Mount Sinai in New York, Virginia Commonwealth University School of Medicine, and Hadassah University in Israel.

Piclidenoson (CF101): ACRobat Phase III Trial in Rheumatoid Arthritis to Commence

In August 2017, Can-Fite successfully concluded a cardiodynamic trial for its lead drug candidate Piclidenoson, which showed favorable safety data required by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) prior to initiation of Phase III studies.

During the second quarter of 2017, Can-Fite conducted a successful Clinical Investigator Meeting with approximately 100 rheumatologists, and their staff, who are participating as clinical investigators in the Company’s global pivotal Phase III ACRobat study, which is set to commence patient enrollment in the third quarter of 2017.

ACRobat is a Phase III trial that will evaluate Piclidenoson as a first line treatment and replacement for the current standard of care, Methotrexate (MTX), the most widely used drug for rheumatoid arthritis. The trial will enroll approximately 500 patients in Europe, Canada and Israel. The estimated cost of the entire Phase III study is approximately $5 million. Rheumatoid arthritis is a treatment market forecast to reach $34.6 billion by 2020.

Piclidenoson is also being developed as a treatment for psoriasis. Can-Fite is preparing for an upcoming Phase III trial that will investigate the efficacy and safety of Piclidenoson compared to placebo as its primary endpoint and as compared to apremilast (Otezla) as its secondary endpoint in approximately 400 patients with moderate-to-severe plaque psoriasis. Can-Fite expects to submit its clinical protocol to Institutional Review Boards in the fourth quarter of 2017. The psoriasis market is forecast to be $8.9 billion in 2018 and Otezla sales are estimated to be $2.35 billion by 2020.

“Completion of patient enrollment in our Phase II study is a significant advancement in the development of Namodenoson to treat liver cancer. We will evaluate results as soon as possible based on survival data. There is a clear unmet medical need for HCC patients with Child-Pugh Class B cirrhosis. Our Orphan Drug status in both the U.S. and Europe, as well as Fast Track status in the U.S. in this indication, we believe will accelerate our path towards applying for market approval for Namodenoson for liver cancer,” stated Can-Fite CEO Dr. Pnina Fishman. “In the current quarter, we look forward to commencing patient enrollment in our Phase II NAFLD/NASH study for Namodenoson and our Phase III rheumatoid arthritis study for Piclidenoson.”

Financial Results

Revenues for the six months ended June 30, 2017 were NIS 0.53 million (U.S. $0.15 million) compared to NIS 0.43 million (U.S. $0.12 million) in the first six months of 2016. The increase in revenue was mainly due to the recognition of a portion of the NIS 1.9 million (U.S. $0.5 million) advance payment received in December 2016 under the distribution agreement with CKD.

Research and development expenses for the six months ended June 30, 2017 were NIS 8.84 million (U.S. $2.53 million) compared with NIS 9.97 million (U.S. $2.85 million) for the same period in 2016. Research and development expenses for the first half of 2017 comprised primarily of expenses associated with the Phase II study for Namodenoson, the preclinical study of CF602, as well as expenses for ongoing studies of Piclidenoson. The decrease is primarily due to a reduction in preclinical studies of CF602 conducted during the six months ended June 30, 2017.

General and administrative expenses were NIS 5.0 million (U.S. $1.43 million) for the six months ended June 30, 2017, the same as the general and administrative expenses for the same period in 2016.

Financial income, net for the six months ended June 30, 2017 aggregated NIS 1.57 million (U.S. $0.45 million) compared to financial income, net of NIS 3.19 million (U.S. $0.91 million) for the same period in 2016. The decrease in financial income, net in the first half of 2017 was mainly from exchange rate differences as compared to the same period in 2016 and from issuance expenses, offset by a larger decrease in the fair value of warrants that are accounted for as financial liability as compared to the same period in 2016.

Can-Fite’s net loss for the six months ended June 30, 2017 was NIS 11.72 million (U.S. $3.35 million) compared with a net loss of NIS 11.35 million (U.S. $3.25 million) for the same period in 2016. The slight increase in net loss for the first half of 2017 was primarily attributable to a decrease in financial income, net.

As of June 30, 2017, Can-Fite had cash and cash equivalents of NIS 23.98 million (U.S. $6.86 million) as compared to NIS 31.2 million (U.S. $8.92 million) at December 31, 2016. The decrease in cash during the six months ended June 30, 2017 is due to use of cash to fund operating expenses.

For the convenience of the reader, the reported NIS amounts have been translated into U.S. dollars, at the representative rate of exchange on June 30, 2017 (U.S. $1 = NIS 3.496).

The Company’s consolidated financial results for the six months ended June 30, 2017 are presented in accordance with International Financial Reporting Standards.