On July 4, 2018 Ipsen (Euronext: IPN; ADR: IPSEY) reported that The New England Journal of Medicine (NEJM) published results from the CELESTIAL phase 3 pivotal trial of cabozantinib in patients with previously treated advanced hepatocellular carcinoma (HCC) (Press release, Ipsen, JUL 4, 2018, View Source [SID1234527565]).1 The data, originally presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Gastrointestinal Cancers Symposium (ASCO-GI) in January, demonstrate that cabozantinib provided a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo.

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"Patients with this form of advanced liver cancer have very limited treatment options once their disease progresses following treatment with sorafenib," said Ghassan K. Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center, New York and lead investigator on CELESTIAL. "These results suggest that, if approved, cabozantinib could become an important addition to the treatment landscape that may help slow disease progression and, critically, improve survival for these patients."

"Patients with advanced HCC have a very poor prognosis and limited treatment options. Given the worldwide prevalence of advanced HCC, there is a continued urgency to bring new treatment options to these patients", added Lorenza Rimassa M.D., Deputy Director, Medical Oncology Unit, Humanitas Cancer Center Humanitas Research Hospital, Milan. "The clinically significant benefits in both overall survival and progression-free survival shown in the CELESTIAL trial, in patients previously treated with up to two treatment lines, suggest that cabozantinib could become (when approved) an important addition to the treatment landscape for this patient population."

Ipsen received validation by the European Medicines Agency in March 2018 for its application for variation to the Cabometyx marketing authorization to include the new indication for patients with previously treated advanced HCC. Ipsen’s partner Exelixis announced in May 2018 that the U.S. Food and Drug Administration (FDA) accepted the company’s supplemental New Drug Application (sNDA) for Cabometyx (cabozantinib) tablets as a treatment for patients with previously treated HCC. The filing has been assigned a Prescription Drug User Fee Act action date of January 14, 2019.

"This publication of CELESTIAL phase 3 data in the NEJM this week further validates the medical importance of these results for the treatment of patients with advanced liver cancer" said Alexandre Lebeaut, Executive Vice-President Research & Development, Chief Scientific Officer, Ipsen. "Together with our partner Exelixis we relentlessly contribute to expanding the clinical benefits of cabozantinib across solid tumors to address unmet medical needs".

Median OS in CELESTIAL was 10.2 months with cabozantinib versus 8.0 months with placebo (HR 0.76, 95 percent CI 0.63-0.92; p=0.0049). Median progression-free survival (PFS) was more than doubled, at 5.2 months with cabozantinib and 1.9 months with placebo (HR 0.44, 95 percent CI 0.36-0.52; p<0.0001). Objective response rates per RECIST 1.1 were 4 percent with cabozantinib and 0.4 percent with placebo (p=0.0086). Disease control (partial response or stable disease) was achieved by 64 percent of patients in the cabozantinib group compared with 33 percent of patients in the placebo group.

In a subgroup analysis of patients whose only prior therapy for advanced HCC was sorafenib (70 percent of patients in the study), median OS was 11.3 months with cabozantinib versus 7.2 months with placebo (HR 0.70, 95 percent CI 0.55-0.88). Median PFS in the subgroup was 5.5 months with cabozantinib versus 1.9 months with placebo (HR 0.40, 95 percent CI 0.32-0.50).

Adverse events were consistent with the known safety profile of cabozantinib. The most common (≥10 percent) grade 3 or 4 adverse events in the cabozantinib group compared to the placebo group were palmar-plantar erythrodysesthesia (17 percent vs. 0 percent), hypertension (16 percent vs. 2 percent), increased aspartate aminotransferase (12 percent vs. 7 percent), fatigue (10 percent vs. 4 percent) and diarrhea (10 percent vs. 2 percent). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure). Sixteen percent of patients in the cabozantinib arm and three percent of patients in the placebo arm discontinued treatment due to treatment-related adverse events.

About CELESTIAL
CELESTIAL is a randomized, double-blind, placebo-controlled global phase 3 study of cabozantinib versus placebo in patients with advanced hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. The study was conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced hepatocellular carcinoma (HCC) who previously received sorafenib and may have received up to two prior systemic cancer therapies for hepatocellular carcinoma (HCC) and had adequate liver function. Enrollment of the trial was completed in September 2017, and 773 patients were ultimately randomized. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms.

The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

Based on available clinical trial data from various published trials conducted in the second-line setting of advanced hepatocellular carcinoma (HCC), the CELESTIAL trial statistics for the primary endpoint of OS assumed a median OS of 8.2 months for the placebo arm. A total of 621 events provide the study with 90 percent power to detect a 32 percent increase in median OS (HR = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50 percent and 75 percent of the planned 621 events.

CELESTIAL trial met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in median OS compared to placebo in patients with advanced HCC. The independent data monitoring committee for the study recommended that the trial should be stopped for efficacy following review of the second planned interim analysis. The safety data in the study were consistent with the established profile of cabozantinib.

About HCC

Hepatocellular carcinoma (HCC) is the most common form of liver cancer in adults.2 The disease originates in cells called hepatocytes found in the liver. With approximately 800’000 new cases diagnosed each year, hepatocellular carcinoma (HCC) is the sixth most common cancer and the second-leading cause of cancer deaths worldwide.3,4 According to the GLOBOCAN data, it is estimated that across the European Union (EU-28) nearly 60’000 new patients will be diagnosed with liver cancer in 2020.5 Without treatment, patients with the disease in advanced stage usually survive between 4 and 8 months.6

About CABOMETYX (cabozantinib)

Cabometyx is an oral small molecule inhibitor of receptors, including VEGFR, MET, AXL and RET. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

In February of 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. This agreement was amended in December of 2016 to include commercialization rights for Ipsen in Canada.

On April 25, 2016, the FDA approved Cabometyx tablets for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy and on September 9, 2016, the European Commission approved Cabometyx tablets for the treatment of advanced renal cell carcinoma (RCC) in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. Cabometyx is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

On December 19, 2017, Exelixis received approval from the FDA for Cabometyx for the expanded indication of treatment of first-line advanced RCC .

On May 17, 2018, Ipsen announced that the European Commission approved Cabometyx for the first-line treatment of adults with intermediate- or poor- risk advanced renal cell carcinomain the European Union, Norway and Iceland.

Cabozantinib is not approved for the treatment of advanced hepatocellular carcinoma.

On July 4, 2018 Exelixis, Inc. (Nasdaq: EXEL) reported that The New England Journal of Medicine (NEJM) published results from the CELESTIAL phase 3 pivotal trial of cabozantinib in patients with previously treated advanced hepatocellular carcinoma (HCC) (Press release, Exelixis, JUL 4, 2018, View Source;p=RssLanding&cat=news&id=2357066 [SID1234527564]).1 The data, originally presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Gastrointestinal Cancers Symposium (ASCO-GI) in January, demonstrate that cabozantinib provided a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo.

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"Patients with this form of advanced liver cancer have very limited treatment options once their disease progresses following treatment with sorafenib," said Ghassan K. Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center, New York and lead investigator on CELESTIAL. "These results suggest that, if approved, cabozantinib could become an important addition to the treatment landscape that may help slow disease progression and, critically, improve survival for these patients."

Exelixis announced in May 2018 that the U.S. Food and Drug Administration (FDA) accepted the company’s supplemental New Drug Application (sNDA) for CABOMETYX (cabozantinib) tablets as a treatment for patients with previously treated HCC. The filing has been assigned a Prescription Drug User Fee Act action date of January 14, 2019. Exelixis’ partner Ipsen received validation by the European Medicines Agency in March 2018 for its application for variation to the CABOMETYX marketing authorization to include the new indication for patients with previously treated advanced HCC.

"The publication of the CELESTIAL trial results in a peer-reviewed publication as prestigious as NEJM further validates the importance of these data for the advanced liver cancer community," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "We’re working closely with the FDA as they review our sNDA in order to bring CABOMETYX to this growing patient population as quickly as possible."

Median OS in CELESTIAL was 10.2 months with cabozantinib versus 8.0 months with placebo (HR 0.76, 95 percent CI 0.63-0.92; p=0.0049). Median progression-free survival (PFS) was more than doubled, at 5.2 months with cabozantinib and 1.9 months with placebo (HR 0.44, 95 percent CI 0.36-0.52; p<0.0001). Objective response rates per RECIST 1.1 were 4 percent with cabozantinib and 0.4 percent with placebo (p=0.0086). Disease control (partial response or stable disease) was achieved by 64 percent of patients in the cabozantinib group compared with 33 percent of patients in the placebo group.

In a subgroup analysis of patients whose only prior therapy for advanced HCC was sorafenib (70 percent of patients in the study), median OS was 11.3 months with cabozantinib versus 7.2 months with placebo (HR 0.70, 95 percent CI 0.55-0.88). Median PFS in the subgroup was 5.5 months with cabozantinib versus 1.9 months with placebo (HR 0.40, 95 percent CI 0.32-0.50).

Adverse events were consistent with the known safety profile of cabozantinib. The most common (≥10 percent) grade 3 or 4 adverse events in the cabozantinib group compared to the placebo group were palmar-plantar erythrodysesthesia (17 percent vs. 0 percent), hypertension (16 percent vs. 2 percent), increased aspartate aminotransferase (12 percent vs. 7 percent), fatigue (10 percent vs. 4 percent) and diarrhea (10 percent vs. 2 percent). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure). Sixteen percent of patients in the cabozantinib arm and three percent of patients in the placebo arm discontinued treatment due to treatment-related adverse events.

About the CELESTIAL Study

CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and PFS. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

In October 2017, Exelixis announced that the independent data monitoring committee for the CELESTIAL study recommended that the trial be stopped for efficacy following review at the second planned interim analysis, with cabozantinib providing a statistically significant and clinically meaningful improvement in OS compared with placebo in patients with previously treated advanced HCC. In March 2017, the FDA granted orphan drug designation to cabozantinib for the treatment of advanced HCC.

About HCC

Liver cancer is the second-leading cause of cancer death worldwide, accounting for more than 700,000 deaths and nearly 800,000 new cases each year.2 In the U.S., the incidence of liver cancer has more than tripled since 1980.3 HCC is the most common form of liver cancer, making up about three-fourths of the estimated nearly 42,000 new cases in the U.S. in 2018.3 HCC is the fastest-rising cause of cancer-related death in U.S.4 Without treatment, patients with advanced HCC usually survive less than 6 months.5

About CABOMETYX (cabozantinib)

CABOMETYX tablets are approved in the United States for the treatment of patients with advanced renal cell carcinoma (RCC). CABOMETYX tablets are also approved in the European Union, Norway, Iceland, Australia, Switzerland and South Korea for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy, and in the European Union for previously untreated intermediate- or poor-risk advanced RCC. On March 28, 2018, Ipsen announced that the European Medicines Agency validated its application for a new indication for cabozantinib as a treatment for previously treated advanced HCC in the European Union. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan, including RCC.

CABOMETYX is not indicated for previously treated advanced HCC.

U.S. Important Safety Information

Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
Diarrhea: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Embryo-fetal Toxicity may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

On July 4, 2018 Sumitomo Dainippon Pharma Co., Ltd. (Head Office: Osaka, Japan; Representative Director, President and CEO: Hiroshi Nomura hereinafter called "Sumitomo Dainippon Pharma") reported that it submitted a new drug application for thiotepa (generic name, product code: DSP-1958) in Japan on July 3, for conditioning treatment prior to autologous hematopoietic stem cell transplantation (HSCT) for pediatric solid tumors (Press release, Sumitomo Dainippon Pharma, JUL 4, 2018, View Source [SID1234527555]).

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Thiotepa is an antitumor alkylating agent that belongs to the ethyleneimine group and inhibits DNA synthesis. In Japan, Sumitomo Chemical Co., Ltd. launched this agent as Tesupamin injection in 1958, which was then taken over by Sumitomo Pharmaceuticals Co., Ltd. (current Sumitomo Dainippon Pharma) in 1984. However, following the discontinued production of its active pharmaceutical ingredients in 2008, Sumitomo Dainippon Pharma discontinued its marketing in 2009, and the agent has not been available since then in Japan.

In Japan, thiotepa had no approved indication for conditioning treatment prior to autologous HSCT, but had been put to clinical use in combination with other chemotherapeutic agents by following the precedent set by the U.S. and Europe. In spite of the discontinuation of its marketing in 2009 in Japan, many requests for their use for this indication were made by academic societies and other parties concerned, as thiotepa was approved for conditioning treatment prior to HSCT in Europe in 2010. In response, the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs of the Ministry of Health, Labour and Welfare of Japan (MHLW) determined that the
medical need for thiotepa was high. Accordingly, the MHLW invited private companies to develop the agent for the indication, to which Sumitomo Dainippon Pharma replied in September 2013 and began conducting a Phase 1 study in Japan from November 2016 as a pharmacokinetic study, the results of which are included in the data attached to this application. Meanwhile, Sumitomo Dainippon Pharma is also preparing an application for approval of thiotepa for conditioning treatment prior to autologous HSCT for malignant lymphoma.

Sumitomo Dainippon Pharma expects that thiotepa, if approved, would be a new therapeutic option for patients in areas with high unmet medical needs, such as conditioning treatment prior to autologous HSCT for pediatric solid tumors, contributing to the treatment of patients with such symptoms.

About hematopoietic stem cell transplantation (HSCT) HSCT is a powerful adjuvant therapy that aims to reconstruct hematopoietic capacity via intravenous transfusion of normal hematopoietic stem cells after eradicating intractable cancer by performing conditioning myeloablative treatment prior to transplantation using maximum levels of
anti-cancer drugs or radiation. Since patients’ own hematopoietic stem cells are collected and preserved beforehand, autologous HSCT is free from concerns about immunoreactions to transplanted hematopoietic stem cells. As such, this conditioning treatment prior to transplantation aims to eradicate tumor cells as much as possible through high-dose chemotherapy using anticancer drugs in doses that exceed the maximum tolerance of bone marrow. According to the Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT), the number of HSCT cases in Japan totaled 93,902 between 1986 and 2016, among which 33,527 cases were autologous HSCT.

About Pediatric Solid Tumors
According to the Practical guidelines for pediatric cancer 2016, approximately 2,500 new cases ofpediatric cancer occur annually in Japan, with approximately 1,300 new cases of pediatric solid tumors (excluding hematopoietic organ tumors, such as leukemia). Compared to solid tumors in adults, pediatric solid tumors demonstrate favorable chemosensitivity. As a result, better outcome of high-dose chemotherapy combined with HSCT is expected, and transplantation is now being performed as a part of everyday clinical practice. According to the JDCHCT, the number of HSCT cases for pediatric sold tumor patients totaled 3,276 between 1991 and 2016, among which 3,058
cases were autologous HSCT.

About the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs
The Evaluation Committee on Unapproved or Off-label Drugs with High Medical Needs is a committee established to promote the development of unapproved or off-label drugs by pharmaceutical companies that are approved for use in Europe and the United States, etc., but not approved in Japan. It is organized by the MHLW and consists of academic experts in medical and pharmaceutical fields.

On July 3, 2018 MabVax Therapeutics Holdings, Inc. (Nasdaq: MBVX), a clinical stage oncology drug development company reported that it has granted to Y-mAbs Therapeutics, Inc., a privately held clinical stage biopharmaceutical company, an exclusive sublicense to a bi-valent ganglioside based vaccine intended to treat neuroblastoma, a rare pediatric cancer (Press release, MabVax, JUL 3, 2018, View Source [SID1234527551]). A third of neuroblastoma patients are diagnosed as infants; and ninety percent are younger than five years of age at time of diagnosis. Neuroblastoma is responsible for twelve percent of all cancer deaths in children less than 15 years of age.

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The neuroblastoma vaccine was originally developed by Dr. Philip Livingston and colleagues at Memorial Sloan Kettering Cancer Center (MSK) and licensed as part of a broader portfolio of anti-cancer vaccines to MabVax. MabVax filed for and was granted an Orphan Drug Designation for the neuroblastoma vaccine and has manufactured Phase II clinical supplies for a planned but not initiated clinical trial to be conducted with the consortium New Advances in Neuroblastoma Therapy (NANT). NANT is the only consortium of academic medical centers in the world solely dedicated to developing novel treatments and biomarkers for children with Neuroblastoma. Over the last several years MabVax has shifted its focus and resources to the Company’s human antibody discovery and development programs that are currently in early stage clinical trials and have attracted partner interest.

Y-mAbs Therapeutics, Inc ("Y-mAbs") is a clinical-stage biopharmaceutical company developing novel antibody therapeutics for oncology targets based on a range of technologies licensed from MSK under an exclusive worldwide license and research collaboration agreement. The Company has two antibody based products in advanced clinical trials for the treatment of neuroblastoma and other cancers.

Total value of the transaction to MabVax is $1.3 million plus a share of a Pediatric Disease Voucher if granted by the U.S. Food and Drug Administration ("FDA") to Y-mAbs on approval of the vaccine and the Pediatric Disease Voucher is subsequently sold. Additionally, Y-mAbs will be responsible for all further development of the product as well as any downstream payment obligations related to this specific vaccine to MSK that were specified in the original MabVax-MSK license agreement. If Y-mAbs successfully develops and receives FDA approval for the Neuroblastoma vaccine, it is obligated to file with the FDA for a Pediatric Disease Voucher. If the voucher is granted to Y-mAbs and subsequently sold, then MabVax will receive a percentage of the proceeds from the sale of the voucher by Y-mAbs.

David Hansen, President and CEO of MabVax Therapeutics, explained, "Y-mAbs is ideally positioned to continue the development of the Neuroblastoma vaccine because of their experience in immunotherapy generally and neuroblastoma specifically. If Y-mAbs is successful in development of this product, MabVax will see a greater financial benefit through participation in the sale of the Pediatric Disease Voucher."

On July 3, 2018 Eagle Pharmaceuticals, Inc. (Nasdaq:EGRX) ("Eagle" or "the Company") reported that an additional patent has been issued related to BENDEKA by the United States Patent and Trademark Office (USPTO) (Press release, Eagle Pharmaceuticals, JUL 3, 2018, View Source [SID1234527546]). Patent number 10,010,533 will expire January 2031. The USPTO has now issued or allowed a total of 15 patents in the BENDEKA family of patents expiring from 2026 to 2033.

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The newly issued patent will be listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) bringing Eagle’s total Orange Book listed patents for BENDEKA to thirteen1. Furthermore, as a result of a Court decision issued on June 8, 2018, BENDEKA now has Orphan Drug Exclusivity (ODE). The FDA will not be able to approve any drug applications referencing BENDEKA until the ODE expires in December 2022. Moreover, the Company now does not expect generic TREANDA entrants into the market until December 2022, rather than November 2019.

"We believe that with the recent positive ODE decision and the strength of our intellectual property portfolio, BENDEKA has longevity well beyond 2022," stated Scott Tarriff, Chief Executive Officer of Eagle Pharmaceuticals.

Under a February 2015 exclusive license agreement for BENDEKA, Teva Pharmaceutical Industries, Ltd. is responsible for all U.S. commercial activities for the product including promotion and distribution.