On November 12, 2019 AVEO Oncology (NASDAQ: AVEO) reported financial results for the third quarter ended September 30, 2019 and provided a business update (Press release, AVEO, NOV 12, 2019, View Source [SID1234551002]).
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"This quarter we have made meaningful progress toward our goal of bringing effective and better tolerated therapies to patients battling kidney and other cancers," said Michael Bailey, president and chief executive officer of AVEO. "We are working to submit our New Drug Application (NDA) in the first quarter of 2020 for tivozanib as a treatment for relapsed/refractory renal cell carcinoma (RCC) and to provide a final overall survival (OS) update for the TIVO-3 study in June 2020. We also continue to make progress in evaluating tivozanib-immunotherapy combinations, with recently reported positive results from the TiNivo study of tivozanib and OPDIVO (nivolumab) in RCC and the initiation of the Phase 1b/2 DEDUCTIVE study with IMFINZI (durvalumab) in hepatocellular carcinoma. Ficlatuzumab also continues to advance in the clinic, with the initiation of CyFi-2, a Phase 2 randomized study in patients with relapsed and refractory acute myeloid leukemia (AML). Critical to this progress, we continue to maintain a strong balance sheet that we believe provides us with a cash runway into the second quarter of 2021."
Tivozanib North America Regulatory and Phase 3 TIVO-3 Study Updates
Announced Plans for TIVO-3 Final OS Analysis and NDA Submission for Tivozanib. Last week, AVEO provided a regulatory update following a meeting with the U.S. Food and Drug Administration (FDA) to discuss results from the August 2019 OS analysis of the TIVO-3 trial and the Company’s proposal to proceed with an NDA for tivozanib in relapsed/refractory RCC.
The Company intends to submit an update to the TIVO-3 statistical analysis plan to the FDA allowing for the final OS analysis to be conducted, followed by an NDA submission in the first quarter of 2020, and expects to report results from the final OS analysis of the TIVO-3 trial in June 2020. The FDA and the Company agreed that if, during the review, the final analysis yields an OS hazard ratio (HR) above 1.00, the Company will withdraw its NDA application. The FDA informed the Company that an Oncologic Drugs Advisory Committee panel would likely be convened to review the final tivozanib data package.
TIVO-3 is the Company’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib, the Company’s vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI), to sorafenib in 350 subjects with highly refractory metastatic RCC.
Announced Updated Overall Survival HR of 0.99 in Phase 3 TIVO-3 Trial of Tivozanib in RCC. In September 2019, AVEO announced results from the second prespecified analysis of OS in the TIVO-3 trial. These results included an OS HR, which assesses the relative risk of death for the entirety of the dataset, that was below 1.00 (HR=0.99; 95% CI: 0.76-1.29; p=0.95).
The data cutoff date for the second prespecified analysis was August 15, 2019, two years from the last patient enrolled and approximately ten months from the data cutoff date for the first prespecified analysis. Between the two data cutoff dates, 16 additional OS events were reported on the tivozanib arm and 28 on the sorafenib arm, resulting in a total of 114 OS events on the tivozanib arm and 113 on the sorafenib arm. Median OS, a point in time value of the OS when half of the patients within each arm are still alive, was 16.4 months for tivozanib (95% CI: 13.4-22.2) and 19.7 months for sorafenib (95% CI: 15.0-24.2). As of the second data cutoff date, twenty patients remained progression free on the tivozanib arm and two on the sorafenib arm, with a median duration on study of 32.5 months.
Updated Data from TIVO-3 Trial to be Presented at the 18th International Kidney Cancer Symposium. Updated data from the TIVO-3 trial will be presented during an oral session at the 18th International Kidney Cancer Symposium being held November 15-16, 2019 in Miami. The presentation, titled "Overall Survival from Phase 3 TIVO-3 Study in Advanced Renal Cell Carcinoma", will be presented on Saturday, November 16 at 9:42 a.m. Eastern Time. The presentation will include the recently announced OS data, as well as new data from important subgroups. A copy of the slides will be available in the Publications & Presentations Section of AVEO’s website following the presentation.
Additional Tivozanib Updates
Announced Initiation of Enrollment in Phase 1b/2 DEDUCTIVE Study of Tivozanib in Combination with IMFINZI (durvalumab) in Previously Untreated Metastatic HCC. In September 2019, AVEO announced the initiation of enrollment in the DEDUCTIVE trial, an open-label, multi-center Phase 1b/2 clinical trial evaluating tivozanib in combination with IMFINZI (durvalumab), AstraZeneca’s human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with HCC who have not received prior systemic therapy. The trial is being conducted as part of a clinical collaboration between AVEO and AstraZeneca. AVEO is serving as the study sponsor, with study costs shared equally by both parties and clinical drug supplied by each respective company.
Presented Final PFS Results from Phase 2 Portion of the TiNivo Study of Tivozanib and OPDIVO (nivolumab) in Advanced or Metastatic RCC. In September 2019, AVEO and EUSA Pharma announced the presentation of final progression free survival (PFS) results from the Phase 2 portion of the TiNivo study, a Phase 1b/2 multicenter trial of tivozanib in combination with OPDIVO (nivolumab), Bristol-Myers Squibb’s immune checkpoint, or PD-1, inhibitor, for the treatment of advanced or metastatic RCC. The data were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Annual Congress in Barcelona, Spain.
The combination required few dose reductions and showed additive or synergistic activity for objective response rate and PFS in both treatment naïve and previously treated patients with metastatic RCC. Overall median PFS for the 25 patients treated at the study’s full dose and schedule was 18.9 months (95% CI: 16.4; NR). Median PFS for previously untreated patients (n=12) was 18.5 months, while median PFS for previously treated patients (n=13) had not yet been reached as of the August 27, 2019 data cutoff date. An objective response rate was observed in 56% of patients (complete responses + partial responses), including one treatment naïve patient (1/12) achieving a complete response, and disease control (complete response + partial response + stable disease) was observed in 96% of patients. The most common treatment-related Grade 3/4 adverse event was hypertension, and only 17% of patients required a dose reduction.
A copy of the presentation is available in the Publications & Presentations Section of AVEO’s website.
Announced Kyowa Kirin Buy Back of Tivozanib Non-Oncology Rights from AVEO. In August 2019, AVEO and Kyowa Kirin Co., Ltd. announced that the companies’ license agreement for tivozanib has been amended to allow Kyowa Kirin to buy back the non-oncology rights of tivozanib in AVEO’s territories, which includes the U.S. and EU. Under the terms of the amended license agreement, AVEO received a $25 million upfront payment and a waiver of the $18 million milestone payment due to Kyowa Kirin upon AVEO obtaining U.S. market approval for tivozanib. In addition, AVEO will be eligible to receive up to $391 million in milestone payments upon the successful achievement of certain development and commercial objectives related to tivozanib formulations for the treatment of non-oncology indications. AVEO is also eligible to receive tiered royalty payments on net sales in these indications, which range from a high single-digit to low double-digit percent.
Ficlatuzumab Update
Initiation of the CyFi-2 Study of Ficlatuzumab in Relapsed and Refractory AML. Last week, AVEO and Biodesix, Inc. announced the initiation of the CyFi-2 study, a randomized Phase 2 clinical study evaluating ficlatuzumab, AVEO’s potent hepatocyte growth factor (HGF) inhibitory antibody product candidate, in combination with high-dose cytarabine vs. high-dose cytarabine alone in patients with relapsed and refractory AML.
AVEO will sponsor the CyFi-2 study, which is expected to enroll approximately 60 patients with AML who failed induction chemotherapy or who achieved a complete response but relapsed within one year. The CyFi-2 study is being conducted as part of the companies’ worldwide partnership to develop and commercialize ficlatuzumab. Under the terms of this agreement, AVEO and Biodesix equally share all development costs.
Recent Corporate Update
Appointment of Key Regulatory, Commercial and Medical Affairs Leadership Roles. AVEO announced today the appointment of three individuals to key leadership roles during the fourth quarter:
Darlene Noci, Interim Head of Regulatory Affairs. Ms. Noci brings to AVEO over 20 years of leadership experience in global regulatory affairs and strategic drug development. She received a Bachelor’s degree in Political Science from Adelphi University and a Master’s degree in Government from Harvard University.
Kevin Peacock, Vice President of Marketing. Mr. Peacock brings over 15 years of commercial leadership experience in oncology marketing, strategic planning, and business analytics. He received his Bachelor’s degree in Business Administration from Temple University.
Daniel Powers, D.O., Vice President of Medical Affairs. Dr. Powers brings to AVEO over 20 years of clinical, academic, and biopharmaceutical medical affairs experience. He received his Bachelor’s degree in Chemistry from the University of Massachusetts Boston and a Doctor of Osteopathic Medicine degree from Rowan University. He completed his internship and residency in Internal Medicine at Yale-New Haven Hospital and National Navy Medical Center.
Third Quarter 2019 Financial Results
AVEO ended Q3 2019 with approximately $57.7 million in cash, cash equivalents and marketable securities as compared with $24.4 million at December 31, 2018.
Total revenue for Q3 2019 was approximately $25.7 million compared with $2.5 million for Q3 2018.
Research and development expense for Q3 2019 was $4.0 million compared with $5.2 million for Q3 2018.
General and administrative expense for Q3 2019 was $2.9 million compared with $2.7 million for Q3 2018.
Net income for Q3 2019 was $16.4 million, or net income of $0.10 per basic and diluted share, respectively, compared with a net loss of $22.2 million for Q3 2018, or a loss of $0.18 per basic and diluted share, respectively.
On August 1, 2019, as scheduled and included in the Company’s cash guidance below, the Company resumed principal payments of approximately $0.8 million per month on the $20.0 million Hercules loan that matures on July 1, 2021.
Financial Guidance
AVEO believes that its cash, cash equivalents and marketable securities of approximately $57.7 million at September 30, 2019 would allow the Company to fund its planned operations into the second quarter of 2021. This estimate is a change from the Company’s prior quarter guidance as a result of the Company’s plan to file an NDA for tivozanib, reflecting additional costs related to the NDA filing, as well as limited commercial launch-readiness activities.
About Tivozanib (FOTIVDA)
Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway, New Zealand and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC4. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.
About Ficlatuzumab
Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) inhibitory antibody that binds to the HGF ligand with high affinity and specificity to inhibit HGF/c-Met biological activities. AVEO and Biodesix, Inc. have a worldwide agreement to develop and commercialize ficlatuzumab. Ficlatuzumab is currently being evaluated in squamous cell carcinoma of the head and neck (SCCHN), metastatic pancreatic ductal cancer (PDAC), and acute myeloid leukemia (AML).