Why Incyte’s Product Epacadostat’s Positive Results Are So Important

As a matter of fact, we consider Incyte’s (INCY) drug epacadostat’s good results extremely important. The reason? Two facts are currently settled in researchers’ and oncologists’ minds. These are:

1. Checkpoint inhibitors require effective combination therapy to boost their limited efficacy, or at least to improve their efficacy, especially in solid tumors.

2. IDO inhibition is recognized as central for immunotherapy success.

Both facts have been proven through experimentation with checkpoint inhibitors as monotherapy, and experimentation with them in combination with other products.

In current news, Incyte announced the publication of new data from the ongoing ECHO-202 study evaluating its selective IDO1 enzyme inhibitor, in combination with Keytruda®, a checkpoint inhibitor belonging to Merck’s.

From abstracts published online by ASCO prior to its annual meeting in Chicago, in early June, ECHO-202 Phase 1/2 efficacy and safety data demonstrate the following:

The combination therapy was well-tolerated and preliminary efficacy outcomes for these cohorts demonstrate encouraging clinical activity, both within and across tumor types. The tumors include: Non-small- cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, squamous cell carcinoma of the head and neck (SCCHN), triple-negative breast cancer (TNBC), and ovarian cancer (OVC).

Epacadostat + Keytruda in the ECHO-202 trial boosted the overall response rate (ORR), compared to historical data for Keytruda used on its own.

For non-small cell lung cancer, and bladder cancer, the combination achieved an ORR of 35%. In the head and neck cancer and kidney cancer the combination results were 31% and 30% response rate, respectively.

Three patients demonstrated complete clearance of their tumors.

Important noting that prior studies suggested that using Keytruda as a monotherapy the (ORR) rates were 20% or less in these cancers.

“The data, including updated data which will be presented at ASCO next month, support the recently-announced progression of the epacadostat and pembrolizumab combination into pivotal trials in NSCLC, RCC, bladder cancer and SCCHN,” said Steven Stein, M.D., Incyte’s Chief Medical Officer.

The ECHO clinical trial program was established to investigate the efficacy and safety of epacadostat as a core component of combination therapy in oncology.

Ongoing Phase 1 and Phase 2 studies evaluating epacadostat in combination with PD-1 and PD-L1 inhibitors plan to enroll over 900 patients in a broad range of solid tumor types as well as hematological malignancies.

ECHO-301 (NCT02752074), a Phase 3 randomized, double-blind, placebo-controlled study investigating Keytruda + epacadostat or placebo for unresectable or metastatic melanoma, is also underway.

Epacadostat is a selective oral inhibitor of the IDO1 enzyme that regulates the tumor immune microenvironment, thereby restoring effective anti-tumor immune responses.

In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors demonstrated proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, epacadostat + ipilimumab (CTLA-4 inhibitor) or epacadostat + Keytruda improved response rates compared with studies of the immune checkpoint inhibitors alone.

Prohost Observations

We reiterate our belief that IDO pathway inhibitors will play a big role in improving the checkpoint inhibitors’ efficacy in treating cancers, especially solid tumors. Invcyte is not alone in designing and developing IDO inhibitors, other companies are also developing the same. However, the same does not mean that the molecules are typical.

In the upcoming Prohost Letter #409, we start with a comprehensive review article about a small firm whose IDO inhibitor is demonstrating it has improved on a checkpoint inhibitor efficacy results when the products were used in combination therapy. In the same issue we Present another small firm with a different drug, which is not an IDO inhibitor, yet, showing promise in improving the efficacy of checkpoint inhibitors.

In the articles we state that the competition in this case will not have a real negative impact on products’ sales when approved.

The market is huge.

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