Practice Case #2 | Clearview

The client is a large, multinational biotechnology firm that is developing three novel therapies for acute myeloid leukemia (AML). AML is a rare, extremely aggressive form of blood cancer that is characterized by multiple molecular and cytogenetic mutations that are heterogeneous across patients. Patients are typically elderly (>60 years), although it sometimes develops in younger patients as well. Currently, a typical AML treatment takes the form of intensive chemotherapy treatments, or administration of hypomethylating agents, depending on the age and health/fitness of the patient. Survival rates for patients are very low, and a significant portion of sufferers relapse following initial treatment. Our client has three very early-stage agents: two oral pills each inhibiting a distinct disease-related biomarker, and one IV infusion that is an immuno-oncology agent that engages T cells against any cell expressing a specific antigen, which is expressed broadly on leukemic cells, but also some healthy cells as well.

Question A

The client wants an understanding of the addressable patient population for their products, specifically the incident population across all ages in the U.S. How many patients could be candidates for the client’s three agents in a given year? The client has shared a few data points they have collected on their own: incidence for individuals <60: ~1/100,000; incidence for individuals >60: ~10/100,000. What is the annual incidence then for AML? (click for answer)

Need to assume ~320 M population of U.S. Also may assume that there are roughly an equal number of people at any given age, with an average lifespan of 80 years. This means there are ~4 M people at every age. 1/100k should be applied to 240 M people younger than 60 (60*4 M), and 10/100 K should be applied to 80 M people older than 60.

This leaves ~2,400 people younger than 60, and 8,000 older than 60, for a total of ~10400 incident patients annually in the U.S.

For a disease such as AML, what would you guess is the diagnosis and treatment rate?

Question B

Treatment of AML can really be divided into four stages: the first is called induction, where patients are administered short bouts of high-intensity chemotherapy to de-bulk their leukemic cells. Following induction is consolidation, where additional chemotherapy is administered in order to further push a patient into remission. Next, the patient enters the maintenance phase, or a longer-term therapy meant to prevent re-emergence of leukemic cells. If a patient relapses or is refractory to initial treatments, they enter the salvage stage, where further intensive chemotherapy treatments are applied. The client has three agents: two small molecule inhibitors and the one immuno-oncology (IO) product. The client believes IO has large potential in AML, but wants a recommendation. Based on the drug’s mechanism of action, which of the treatment settings may be best to target, and why? (click for answer)

Answer should be at any of the high-bulk disease stages (induction, consolidation, and salvage), but what will matter is the scientific reasoning behind the decision. High-bulk disease may be a good place for IO due to its ability to directly engage leukemic cells as opposed to simply add cytotoxic agents and hope for the best. The downside is that it may also target healthy cells (e.g., granulocytes, lymphocytes), which may be a reason to not administer in a long-term maintenance setting.

Question C

The client is developing three assets for one indication – what are some pros and cons of having multiple agents in development for a single disease? (click for answer)

Answers can include: Pros: More shots on goal if one fails, ability to increase revenue stream if all successful but can combine, reach wider swath of patients, reduces impact of competitors. Cons: Higher development costs, cannibalization in small patient population if drugs not differentiated enough.