On March 23, 2018 Eisai Co., Ltd. and Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the multiple receptor tyrosine kinase inhibitor LENVIMA (lenvatinib mesylate) has been approved in Japan for unresectable hepatocellular carcinoma (HCC) (Press release, Merck & Co, MAR 23, 2018, View Source [SID1234525467]). This is the first approval worldwide for LENVIMA for the indication of unresectable HCC and the first new systemic therapy to be approved in Japan for the front line treatment of HCC in approximately 10 years. Additionally, this is the first regulatory approval for LENVIMA under the global strategic collaboration agreement executed in March 2018 between Eisai and Merck for the co-development and co-commercialization of LENVIMA.

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This approval was based on a phase 3 clinical study (Study 304/REFLECT study) conducted by Eisai investigating LENVIMA as a first-line treatment in patients with unresectable HCC. In this study, LENVIMA demonstrated statistically significant non-inferiority of overall survival (OS) (13.6 months) compared to sorafenib (12.3 months) (hazard ratio [HR] 0.92, 95% confidence interval [CI]=0.79-1.06). Additionally, LENVIMA showed highly statistically significant and clinically meaningful improvements as compared to sorafenib in the secondary endpoints of progression-free survival (PFS) (HR 0.66, 95% CI=0.57-0.77, p<0.00001), time to progression (TTP) (HR 0.63, 95% CI=0.53-0.73, p<0.00001), and objective response rate (ORR) (LENVIMA 24% versus sorafenib 9%, p<0.00001). Furthermore, LENVIMA helped to delay deterioration in several quality of life (QOL) and symptom domains (pre-specified secondary endpoint), including in areas such as pain and diarrhea, compared to sorafenib (nominal p-value<0.05).

In this study, the five most common adverse events observed in the LENVIMA arm were hypertension (42%), diarrhea (39%), decreased appetite (34%), weight loss (31%) and fatigue (30%), which is consistent with the known safety profile of LENVIMA.

Liver cancer is the second leading cause of cancer-related deaths, with approximately 750,000 deaths per year estimated globally. Additionally, approximately 780,000 cases are newly diagnosed each year, about 80 percent of which occur in Asia, including Japan and China. HCC accounts as the primary reason for 85 percent to 90 percent of liver cancer cases. It is estimated that there are approximately 42,000 HCC patients in Japan, with approximately 26,000 deaths every year. To date, treatment options for unresectable HCC have been limited, and the prognosis is very poor, emphasizing that this is an area of high unmet medical need.

"With the approval of this additional indication of unresectable HCC for LENVIMA, we are proud to be able to deliver the first new front-line systemic therapy treatment option for HCC in Japan in approximately 10 years, and expect this will contribute to HCC treatment," said Dr. Takashi Owa, Eisai Oncology Business Group Chief Medicine Creation Officer. "Eisai will continue with its efforts in oncology research and development in order to deliver hopes for a potential cure for cancer to patients and their families."

"Today’s approval is an important first for LENVIMA and a significant first regulatory event under our collaboration with Eisai," said Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories. "We congratulate Eisai on the approval of this new indication and look forward to working together to bring this important treatment option to patients."

Having received approval of this indication, Eisai will receive a development milestone payment from Merck. There are no changes to Eisai’s consolidated financial results forecasts for the fiscal year ending March 31, 2018 based on the receipt of this milestone payment.

LENVIMA Product Details in Japan (underlined parts have been added)

1) Product name

LENVIMA Capsule 4 mg

2) Generic name

Lenvatinib mesylate

3) Indication

Unresectable thyroid cancer, unresectable hepatocellular carcinoma

4) Dosage and Administration

Unresectable thyroid cancer

The usual adult dose is 24 mg as lenvatinib administered orally once a day. The dose may be reduced depending on the condition of the individual patient.

Unresectable hepatocellular carcinoma

The usual adult dose is an amount of lenvatinib in accordance with body weight administered orally once a day. For adults weighing 60 kg and over, the dose should be 12 mg. For adults weighing less than 60 kg, the dose should be 8 mg. The dose may be reduced depending on the condition of the individual patient.

About LENVIMA (lenvatinib mesylate) capsules, 10 mg and 4 mg

Discovered by Eisai, LENVIMA is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

Currently, LENVIMA is approved as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, in Europe and Asia. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a treatment for renal cell carcinoma (second-line) in over 40 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma.

Outside of Japan, Eisai has submitted applications for an indication covering hepatocellular carcinoma in the United States and Europe (July 2017), China (October 2017), Taiwan (December 2017) and other countries

On March 23, 2018 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that the European Union’s (EU) European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the granting of a conditional marketing authorization for Rubraca as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum based chemotherapy, and who are unable to tolerate further platinum based chemotherapy (Press release, Clovis Oncology, MAR 23, 2018, View Source [SID1234525457]).

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The European Marketing Authorization application for the treatment indication was based on objective response rate and duration of response results from two multicenter, single-arm, open-label clinical trials, Study 10 and ARIEL2, in women with advanced BRCA mutant ovarian cancer who had progressed after two or more prior chemotherapies.

"The recommendation to approve Rubraca as monotherapy is welcome news, as once approved it will offer a new treatment option for women with advanced, recurrent ovarian cancer who have BRCA mutant platinum sensitive disease and are unsuitable for platinum based chemotherapy. In this analysis, we observed many women benefiting from extended progression-free survival with acceptable tolerability," said Dr. Rebecca Kristeleit, Clinical Senior Lecturer and Consultant Medical Oncologist, University College London/University College London Hospitals UK. "These are really important data demonstrating meaningful efficacy and a new non-chemotherapy treatment option for this group of patients who have already been exposed to a number of chemotherapy regimens."

Ovarian cancer is the sixth deadliest cancer amongst women in Europe, where more than 65,000 women are diagnosed annually.i Ovarian cancer is challenging to treat, and most women will relapse after surgery and chemotherapy. The 80 to 85 percent of women diagnosed in the later stages of the disease (III and IV) have particularly poor outcomes.ii Approximately one in four women with ovarian cancer have a germline or somatic BRCA mutation,iii and new treatment options are needed to treat unique patient populations.

"We are extremely pleased to have received a positive recommendation for approval for Rubraca in an ovarian cancer treatment indication, and we look forward to receiving the formal approval from the European Commission in second quarter 2018," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "This is great news for women living with this difficult disease who often have limited options available. In addition, this opinion from CHMP paves the way for the review of Rubraca in the ovarian cancer maintenance indication, based on the ARIEL3 data. We intend to file a variation to the Marketing Authorization (MA) in June, with a potential recommendation for approval in the broader maintenance indication by the end of 2018."

Pending approval for the treatment indication, Clovis plans to submit the variation to the MA based on data from the phase 3 ARIEL3 clinical trial, which found that rucaparib significantly improved progression-free survival in all ovarian cancer patient populations studied. ARIEL3 is a double-blind, placebo-controlled trial of rucaparib that enrolled 564 women with platinum-sensitive, high-grade ovarian, fallopian tube, or primary peritoneal cancer. The primary efficacy analysis evaluated three prospectively defined molecular sub-groups in a step-down manner: 1) BRCA mutant (BRCAmut+); 2) HRD positive (HRD+) inclusive of BRCA mutant; and finally, 3) the intent-to-treat population, or all patients treated in ARIEL3. The study achieved its primary endpoint of improved PFS by investigator review in each of three populations. The variation to the MA will be directed at the broader intent-to-treat or "all comers" population.

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in ovarian cancer as well as several additional solid tumor indications. Studies open for enrollment or under consideration include ovarian, prostate, breast, gastroesophageal, pancreatic, lung and bladder cancers. Clovis holds worldwide rights for Rubraca.

In the United States, Rubraca is approved on an accelerated basis as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer, who have been treated with two or more chemotherapies, and selected for therapy based on an FDA-approved companion diagnostic for Rubraca. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. In December 2017, the U.S. Food and Drug Administration (FDA) accepted the Company’s supplemental New Drug Application (sNDA) for Rubraca for a second-line or later maintenance treatment indication in ovarian cancer based on the ARIEL3 data. The FDA granted Priority Review status to the application with a Prescription Drug User Fee Act (PDUFA) date of April 6, 2018.

Rubraca is an unlicensed medical product outside of the U.S.

On March 23, 2018 Amgen (NASDAQ:AMGN) and Allergan plc. (NYSE:AGN) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for the marketing authorization of ABP 980, a biosimilar to Herceptin (trastuzumab) (Press release, Amgen, MAR 23, 2018, View Source;p=RssLanding&cat=news&id=2339486 [SID1234525391]). ABP 980 has been recommended for approval for the treatment of the same three types of cancer as Herceptin is approved for in the European Union (EU), including HER2-positive metastatic breast cancer, HER2-positive early breast cancer and HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction.

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"The positive opinion issued by the CHMP for ABP 980 marks an important step for our biosimilar portfolio, as it’s our second oncology biosimilar to reach this important milestone, and further underscores our commitment to providing the oncology community access to high-quality cancer therapies," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We look forward to continuing our work with Allergan and European regulatory authorities to bring additional options to patients with cancer."

The Marketing Authorization Application for ABP 980 was supported by analytical, pharmacokinetic and clinical data, as well as pharmacology and toxicology data. The Phase 3 comparative efficacy, safety and immunogenicity study was conducted in adult female patients with HER2-positive early breast cancer.

"We are committed to providing patients with important medicines to help them fight cancer," said David Nicholson, chief research and development officer at Allergan. "The CHMP’s positive opinion for the marketing authorization of ABP 980 reinforces its potential to increase physician choice and patient access to an important biologic."
The CHMP positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the EU. If approved, a centralized marketing authorization will be granted that will be valid in the 28 countries that are members of the EU. Norway, Iceland and Liechtenstein, as members of the European Economic Area (EEA), will take corresponding decisions on the basis of the EC’s decision.

Amgen and Allergan are collaborating on the development and commercialization of four oncology biosimilars. Amgen has a total of 10 biosimilars in its portfolio, two of which have been approved by the EC.
About ABP 980

ABP 980 is being developed as a biosimilar to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody approved in many regions for the treatment of HER2-overexpressing early breast cancer, adjuvant breast cancer, metastatic breast cancer and metastatic gastric cancer. The active ingredient of ABP 980 is a humanized monoclonal antibody that has the same amino acid sequence as trastuzumab. ABP 980 has the same pharmaceutical dosage form and same strength after reconstitution as trastuzumab. Amgen and Allergan also submitted a Biologics License Application to the U.S. Food and Drug Administration (FDA) for ABP 980 in 2017.

On March 23, 2018 Euronext Paris: FR0010331421 – IPH) reported that its partner MedImmune, AstraZeneca’s global biologics research and development arm, has amended the clinical trial protocol of the ongoing Phase I trial investigating the safety and efficacy of monalizumab, Innate’s investigational first-in-class anti-NKG2A monoclonal antibody, in combination with AstraZeneca’s approved anti-PD-L1 immune checkpoint inhibitor, durvalumab, in patients with advanced solid tumors (Press release, Innate Pharma, MAR 23, 2018, http://www.innate-pharma.com/en/news-events/press-releases/partner-medimmune-expands-colorectal-cancer-patient-cohort-ongoing-phase-i-trial-evaluating-monalizumab-combination-imfinzir-durvalumab [SID1234525390]). The trial protocol has been expanded to add new expansion cohorts aiming at testing monalizumab in combination with durvalumab and standard of care in patients with 1st- and 2nd-line, metastatic colorectal cancer (CRC).

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The dose-escalating part of the study has been completed, while the expansion cohorts in selected advanced solid tumors are ongoing.
The primary objective of the new study arms will be safety, with Overall Response Rate (ORR) and Duration of Response (DOR), amongst others, as secondary outcome measures.
Pierre Dodion, Chief Medical Officer of Innate Pharma, commented: "We are delighted that our partner MedImmune has decided to further expand the colorectal patient population to evaluate the safety and efficacy of monalizumab in combination with durvalumab and the current standard of care in 1st- and 2nd-line therapy. In addition, we look forward to the first clinical data read-outs from the Phase I study and initial expansion cohort program during 2018."
An update to study D419NC00001 including the new additional study arms has been published on clinicaltrials.gov.

On March 23, 2018 Epigenomics AG (Frankfurt Prime Standard: ECX, OTCQX: EPGNY), or the "Company", reported its financial results (according to IFRS) for the year ended December 31, 2017 (Press release, Epigenomics, MAR 23, 2018, View Source [SID1234525127]).

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KEY HIGHLIGHTS

Financial

Total revenue of EUR 1.9 million
EBITDA (before share-based payment expenses) loss of EUR 9.4 million
Liquidity of EUR 13.7 million (incl. marketable securities) at year-end following successful capital raises in 2017
Corporate

Voluntary takeover offer by Summit Hero Holding GmbH in 2017 highlighted inherent value of the Company’s products and technologies
Epigenomics AG gets CE-IVD mark for lung cancer test Epi proLung
First quarter 2018

U.S. Senators Capito and Heinrich introduce Bi-Partisan Colorectal Cancer Detection Bill aiming to provide coverage under the Medicare program for FDA-approved qualifying blood-based colorectal cancer screening tests
Greg Hamilton, Chief Executive Officer of Epigenomics, commented: "In 2017, we remained focused on our key priorities medical guideline inclusion and initial payor coverage for our innovative blood-based colon cancer test, Epi proColon, while maintaining high cost discipline in all company areas. In 2018, we expect to reach significant milestones with regard to Medicare payment and coverage for Epi proColon. The recent bipartisan legislative initiative by U.S. Senators Capito and Heinrich addresses payment as the last remaining barrier for Medicare patients associated with colon cancer screening. The passing of this bill provides to millions of underscreened rural Americans access to colon cancer screening and has the potential to ultimately save thousands of lives."

Financial results

In 2017, Epigenomics’ total revenue decreased to EUR 1.9 million (2016: EUR 4.2 million). In the previous year, our U.S. commercialization partner had initially stocked up on inventories of Epi proColon following the product’s FDA approval. Revenue of about EUR 1.3 million was generated through licensing income, product sales were at EUR 0.5 million.
Total operating costs decreased to EUR 13.2 million (2016: EUR 17.3 million). Research and development costs decreased to EUR 4.3 million (2016: EUR 5.1 million). Selling, general and administrative costs decreased to EUR 8.0 million (2016: EUR 10.2 million).
Operating loss (EBIT) in 2017 decreased to EUR -10.3 million (2016: EUR -12.3 million). Net loss for the year decreased to EUR 10.2 million (2016: EUR 11.2 million) and loss per share decreased to EUR 0.44 (2016: EUR 0.55).
Cash consumption in 2017 decreased to EUR 10.1 million (2016: EUR 13.7 million). Net cash inflows from financing activities reached EUR 11.5 million in 2017 (2016: EUR 17.4 million), net cash flow was at EUR 1.4 million (2016: EUR 3.8 million).
The Company’s liquidity (incl. marketable securities) at year-end 2017 was EUR 13.7 million (Dec 31, 2016: EUR 12.3 million).
Outlook 2018

Revenue

Our business projections for 2018 are based mainly on the commercialization of Epi proColon in the U.S.A. The commercialization of this product depends primarily on securing reimbursement from public and private health insurers. Prior to the entry into force of a reimbursement decision we expect only a slight increase in product revenue in 2018.
Overall, we expect that revenue will increase but will remain on low levels, ranging between EUR 2.0 million and EUR 4.0 million.
EBITDA

We anticipate that EBITDA before share-based payment expenses will be in a range EUR -11.5 million and EUR -14.0 million in 2018.
Cash consumption

Based on our business plans for 2018, we expect cash consumption in line with our EBITDA before share-based payment expenses guidance.
We ended the 2017 fiscal year with EUR 13.7 million in cash and marketable securities. While current financial resources are sufficient at our projected cash consumption to support the Company’s operations beyond 2018, we will raise additional capital if necessary in 2018.
The forecast cash consumption is based on our assumption that the convertible notes maturing as of December 31, 2018 will be converted with no adverse effect on liquidity, or will be extended.
Further Information

The annual report 2017 can be downloaded from Epigenomics’ website at:
View Source

Conference call for analysts and investors

The Company will host a conference call and webcast at 2.30 pm CET / 9.30 am EDT, today. The webcast can be accessed on the Company’s website: View Source

The dial-in numbers for the conference call are:

Dial-in number within Germany: +49 30 233225798

Dial-in number within the UK: +44 20 3872 0880

Dial-in number within the U.S.A.: +1 516-269-8974

Participants are kindly requested to dial in 10 minutes prior to the start of the call.

An audio replay of the conference call will be provided on Epigenomics’ website subsequently.