& Commercializing Targeted
Small Molecule Drugs in Cancer
Fiscal 2018 was a year of significant achievements for Array, as we successfully transitioned to a fully integrated, commercial-stage biopharmaceutical company. The launch of BRAFTOVI™ + MEKTOVI® is just the start, and we are excited to write Array’s next chapter.
FDA Approves BRAFTOVI™ (encorafenib) + MEKTOVI® (binimetinib)
We were thrilled to launch BRAFTOVI™ (encorafenib) in combination with MEKTOVI® (binimetinib) for patients with advanced BRAF-mutant melanoma in the United States, following Food and Drug Administration (FDA) approval on June 27, 2018, and are proud to offer patients a new standard of care for advanced BRAF-mutant melanoma.
BRAFTOVI + MEKTOVI were available for sale beginning on July 2, 2018, and patients began receiving the combination therapy that same week. We are excited to report that early demand from melanoma prescribers for our combination has been very positive. We have seen strong uptake in the academic setting where our data indicates the majority of patients with BRAF-mutant melanoma receive treatment. Based on the therapeutic profile generated from our Phase 3 COLUMBUS trial, including a median overall survival in excess of 30 months, a median progression-free survival of nearly 15 months and an attractive tolerability profile, we are confident that our commercial team is well-positioned for success.
Shortly after approval, the National Comprehensive Cancer Network (NCCN©) updated the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma to include encorafenib (BRAFTOVI) in combination with binimetinib (MEKTOVI) as a Category 1 first-line treatment option for patients with metastatic or unresectable melanoma with a BRAFV600-activating mutation.*
Strong Partnerships Provide Ex-U.S. Commercialization Opportunity
While Array is focused on the U.S. launch of BRAFTOVI + MEKTOVI, we have strong partnerships in place to maximize the potential of the combination around the world. Pierre Fabre, our Europe-focused partner, has a strong legacy in oncology and over a thousand employees dedicated to this therapeutic area, including commercial, research and development capabilities and has made BRAFTOVI + MEKTOVI a top priority for their team. Ono Pharmaceutical Co., Ltd., a Japanese market leader in immuno-oncology, has a powerful track record of success in developing and commercializing oncology products in Japan, with rights to the “first-to-market” anti-PD-1 antibody Opdivo® (nivolumab), and we look forward to their expertise in introducing our products in this important region.
Working with our partners, we have made substantial progress with regulatory agencies over the past year. The European Medicines Agency (EMA) has accepted and validated the BRAFTOVI and MEKTOVI Marketing Authorization Applications and, most recently, the EMA’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of BRAFTOVI + MEKTOVI for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation. The final European Commission decision, expected in the coming weeks, will be applicable to all 28 European Union member states, as well as Liechtenstein, Iceland and Norway. Further, the Manufacturing and Marketing Approval applications have been accepted and are under review by Japan’s Pharmaceuticals and Medical Devices Agency.
Our agreements with Pierre Fabre and Ono expand BRAFTOVI + MEKTOVI’s global reach while providing us with potential milestones and royalties. In aggregate, we stand to receive up to $563 million in remaining potential milestone payments from Pierre Fabre and Ono, and the prospect that over half of future development costs could be offset by contributions from our partners. In Europe and other territories, Pierre Fabre will deliver 35% royalties on annual combined net sales of BRAFTOVI + MEKTOVI, which exceed €100 million, and in Japan and South Korea, Ono will provide 25% royalties on annual combined net sales of both products, which exceed ¥10 billion.
Significant Near-term Opportunity in Colorectal Cancer
Last month we were very pleased to learn that the FDA granted Breakthrough Therapy Designation to the triplet combination of encorafenib, binimetinib and cetuximab for the treatment of adult patients with BRAFV600E-mutant metastatic CRC whose disease has progressed after one or two prior regimens. Patients with BRAFV600E-mutant metastatic CRC have a mortality risk more than double that of metastatic CRC patients without the mutation, and currently there are no therapies specifically approved for this high, unmet-need population. Obtaining Breakthrough Therapy Designation provides us with the opportunity to work closely with the FDA to expedite our effort to bring an important treatment option to these patients in critical need.
In fact, based on consultation with the FDA and EMA, we plan to amend the BEACON CRC protocol to allow for an interim analysis based primarily on confirmed overall response rate (ORR) and durability of response, which would support an accelerated approval submission with positive results. This interim analysis may also support regulatory submissions in other regions, and we anticipate topline results from this analysis in the first half of 2019. This timing allows for the subset of patients required for the interim analysis of ORR to achieve an objective response and for the durability of responses to be appropriately evaluated.
Our enthusiasm for this program continues to be reinforced by the strength of data from the BEACON CRC safety lead-in, which we presented at the 2018 ESMO World Congress on Gastrointestinal Cancer in June. At the time of analysis, the median overall survival had not yet been reached, however, the overall survival data were fully mature through 12.6 months, and the observed overall survival was 62% at one year. We are pleased that excitement among global investigators continues to increase.
Immuno-Oncology Collaborations Strengthen Pipeline
Based on the growing body of preclinical and clinical evidence that MEK inhibition may enhance the activity of immunotherapies, we are investigating the safety and activity of our MEK inhibitor, binimetinib, with leading checkpoint inhibitors. We structured three nonexclusive clinical trial collaborations—one with Bristol-Myers Squibb (BMS), one with Merck and one with Pfizer—to investigate the safety and efficacy of these combinations in several solid tumor populations, including metastatic colorectal cancer patients with microsatellite stable tumors (MSS CRC). Each collaboration is pursuing a unique trial design to explore different clinical approaches.
First, with BMS, we are exploring the combination of binimetinib, nivolumab, an anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, in patients with MSS CRC with a Ras mutation. This trial is supported by BMS and sponsored by Array. Next, with Merck, we are exploring the combination of binimetinib and pembrolizumab, an anti-PD-1 antibody, in patients with MSS CRC. In this trial, we are exploring the combination of binimetinib, pembrolizumab and standard chemotherapy regimens in order to enroll first-line metastatic CRC patients. Merck is sponsoring and funding this trial. Finally, with Pfizer, we are investigating the combination of binimetinib, avelumab, an anti-PD-L1 antibody, and talazoparib to determine whether adding a PARP inhibitor may improve outcomes for these patients. Pfizer is sponsoring and funding this trial. We have designed these three trials to test different combinations, in different indications and across lines of therapy to more fully explore the scientific hypothesis that MEK inhibitors may enhance the activity of immunotherapy checkpoint inhibitors. Overall, these trials will generate clinical data for binimetinib with leading checkpoint inhibitors across several different patient populations. We are excited to share results from these trials when they are available.
We continue to advance a clinical trial of ARRY-382, our wholly-owned, potent, highly selective, small molecule inhibitor of CSF-1R kinase activity, in combination with pembrolizumab, in patients with ovarian or pancreatic cancer or with solid tumors who have progressed following prior anti-PD-1 therapy.
With more than a dozen research and clinical partnerships with leading pharmaceutical and biotech companies supporting additional programs across a range of indications, Array is well-positioned to create lasting value and make a meaningful impact on the lives of patients.
We ended fiscal 2018 with $413 million in cash, cash equivalents and marketable securities.
The Array team is proud that BRAFTOVI + MEKTOVI are now commercially available to patients in the U.S. for the treatment of advanced BRAF-mutant melanoma. We look forward to expanding the combination’s reach around the world and believe we are well-positioned to accomplish this.
Through the support of our employees, clinical investigators, trial participants and investors, Array has become a commercial organization with a strong pipeline that is improving the lives of patients in critical need. We have multiple catalysts with the potential to drive shareholder value over the coming months, and we look forward to another very productive year ahead.
Chief Executive Officer
September 14, 2018
*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma V.3.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed July 12, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.