Over the past year, a variety of promising immunotherapy (I/O) treatments has risen to the forefront of biotech, creating an exciting set of implications surrounding this prevailing breakthrough in modern medicine.
Here is a quick look at current developments, failures and future projections surrounding 2018’s biggest I/O products.
Though Epacadostat’s future is currently undetermined, the I/O product entered 2018 as one of the most anticipated treatments of its kind. The investigational drug had been intended as an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), and had presented intriguing — albeit scrutinized — implications for treatment of melanoma patients in Q1 2018.
However, last month, Incyte announced that it would be ending its late-phase epacadostat program after a “pivotal failure of Keytruda combination,” a setback exposed during nine closely monitored phase 3 trials observing epacadostat in combination with Keytruda (by Merck) and Opdivo (by Bristol-Myers Squibb).
- Projected Sales: Epacadostat originally enjoyed revenue projections of around $3 billion by 2020. However, it has since dropped to a best-case scenario of $600 million.
- Current Clinical Trial Phase: Epacadostat has been withdrawn from phase 3 trials, back into phase 2.
- Results (to date): The Keytruda-combination trial setback does not necessarily spell the end for Epacadostat, but they have challenged Incyte to be more thorough in future trials and mitigate previously unforeseen risks.
Bristol-Myers Squibb’s (BMS) Relatlimab is a Lymphocyte-activation gene 3 (LAG-3) drug designed to fight PD-1 resistance; it works by binding itself to LAG-3 on T-cells, stimulating these cells to attack cancer cells.
Relatlimab began to receive widespread attention when it entered late phase trials in Q3 2017. Like Epacadostat, the treatment saw early potential as a means of treating patients with advanced melanoma. It continues to be investigated, both alone and in combination with other treatments, as a potential treatment for several other types of cancer.
- Projected Sales: Hard-and-fast sales projections for Relatlimab are still generally undetermined.
- Current Clinical Trial Phase: Relatlimab underwent a phase 1/2 study in late 2017, investigating its safety, tolerability, and effectiveness when paired with BMS’s other treatment, Opdivo.
- Results (to date): Aforementioned trials found a general tolerance for the Relatlimab-Opdivo combination, in 68 melanoma patients – with around 11.5 percent of patients responding to the treatment. Currently, this study is undergoing a recruiting process to “further evaluate the combination treatments in patients with melanoma and other solid tumours.”
Yet another I/O partner of BMS, Nektar Therapeutics has been developing its NKTR-214, a CD112 agonist that, like Relatlimab, stimulates the immune system’s T-cells and natural killer cells to attack cancerous tumours. Recently, Nektar has been noticeably proactive in scheduling a variety of trials testing NKTR-214 in combination with other treatments (among them: Opdivo, Keytruda, and Tecentriq).
- Projected Sales: In March, Nektar’s stock was found to have significantly outperformed the industry’s average in a year’s time. However, this stock has fallen by nearly 25% in recent weeks – with some analysts projecting additional drops of up to 15%.
A graph illustrating Nektar’s stock at the time of its March 2017 price drop (Yahoo Finance).
- Current Clinical Trial Phase: Nektar commenced phase 1/2 studies on NKTR-214 last month, in which it tested the treatment in combination with its other I/O treatment, NKTR-262. The primary purpose of these trials was to evaluate the combination’s safety and tested patients’ tolerability.
- Results (to date): Last month’s phase 1/2 results were presented at the American Association for Cancer Research (AACR) Annual Meeting 2018; they observed that “NKTR-262 and NKTR-214 combination demonstrated efficacy in a broad range of syngeneic tumour models with diverse histologies.” The study’s other conclusions can be found here.
Previously, another phase 1/2 study, conducted last November as a joint effort with BMS, reflected a 91% disease control rate among melanoma patients and an 85% rate for patients with renal cell carcinoma.