Apalutamide Pipeline AssessmentExecutive SummaryProstate cancer is the most commonly diagnosed cancer in men in the United States, and the third leading cause of cancer-related deaths. Most prostate cancer–related deaths are due to advanced disease, and at-risk patients generally progress to metastatic CRPC (mCRPC) within in 2-3 years of biochemical failure. Currently there are no products approved for non-metastatic CRPC (nmCRPC).The androgen receptor (AR) pathway plays a critical role for survival and growth of CRPC and is an attractive therapeutic target. Clinical studies have demonstrated that treating the disease with an AR before it has metastasized improves outcomes. Apalutamide (Janssen), a second-generation AR inhibitor will be the first product to be approved for non-metastatic CRPC (nmCRPC), ahead of 2 other ARs also seeking approval for nmCRPC.Prescribers anticipate that apalutamide will be a valuable addition to current drugs used for treatment of high-risk and progressive forms of cancer, providing a therapy to treat earlier and improve metastasis-free survival.With this opportunity there is also concern that use of these drugs in new patient populations with longer treatment duration will result in additional budget impact.Branded prostate cancer therapies are generally found on top tiers as specialty drugs, with prior authorization, step therapy criteria, and quantity limits employed to restrict use. These cost containment measures are expected for apalutamide.Apalutamide prescription growth is anticipated given the unmet need in this space and strong efficacy highlighted in the Janssen press release. A robust payer value proposition and health economic modeling will be crucial to support the commercialization strategy and market access to this new product. A key competitor will be Xtandi with approval in nmCRPC expected by Q4 2018 which may dampen uptake of apalutamide (full implication can be considered upon data read-outs). PC Risk stratification -NCCN Treatment ConsiderationsProstate Cancer patients initially are treated with localized therapy (in absence of metastatic disease) resulting in a reduction in PSA tumor volume.As the disease progresses (increase in PSA/ tumor volume) androgen deprivation therapy (ADT; castration, LHRH analogues) and antiandrogens are used to reduce PSA/tumor volume.Over time, castration-resistance can develop requiring chemotherapy and other therapies to treat metastatic disease.Prostate Cancer disease can progress across several dimensions includingAsymptomatic, symptomaticNon-metastatic, metastaticHormone sensitive, castration resistantPatient Segments across pre-metastatic and metastatic PCApalutamide Product ProfileAR Competitive Landscape A focus on novel/second generation ARs in phase 3 Development Insights/Payer management approach and likely response to apalutamideApalutamide: commercial uptake considerationsPhysician sentiment vs. standard of careApalutamide has activity in the treatment of men with nmCRPC and will likely be a valuable addition to currently available drugs for treatment of high-risk and progressive forms of prostate cancer. Degree of promise for apalutamide for treatment of high-risk and progressive forms of prostate cancer will be based on data compared to other drugs already available in the market- including enzalutamide or abiraterone.Prescribing decisions can be impacted by market access hurdles (patient OOP, restricted formulary, etc.), as well as potential financial incentives for adhering to clinical pathways to control drug spending, increasingly important in the oncology space.Prescription growth is anticipated given the unmet need in this space and strong efficacy highlighted in the Janssen press release. A robust payer value proposition and health economic modeling will be crucial to support the commercialization strategy and market access to this new product.Xtandi (enzalutamide, Pfizer/Astellas) approval in nmCRPC will likely come within 6-9 months of apulatamide approval. Xtandi is well known to urology prescribers (per Pfizer Q3 analyst call) and appears to be prescribed less by medical oncologists. Medical oncologists will likely be key prescribers of AR therapy in nmCRPC to halt progression to mCRPC. Janssen’s Zytiga (abiraterone acetate, an androgen biosynthesis inhibitor) has a different mechanism of action vs. apalutamide and is not expected to directly compete (per a review of current trials in ct.gov, other than a study in mHSPC completed in 12/2016). Apalutamide approval/other AR product approvals in nmCRPC (then HSPC, BRC) will drive expansion of patients considered eligible for therapy with novel AR agents; drug approvals will bring additional headwind in pricing and reimbursement constraints.