Novartis AG (ADR) (NYSE:NVS) just put out data from its lead trial of CTL019 (tisagenlecleucel) and the company is moving considerably on the back of the release. Well, as much as a company of this size can move on a single asset data release, that is. Here’s a look at what’s happened, what the drug’s targeting, how it’s targeting it and what the next step along the development pathway is for Novartis and CTL019.
So, as mentioned, it’s called CTL019, and it’s targeting a lead indication of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adult patients. It’s an immunotherapy asset (as is very much on-trend for development oncology right now) and specifically, it’s a CAR-T type treatment (again, very much on trend).
CAR-T therapies are drugs that attempt to harness a patient’s immune system as a weapon against cancer. They are different from the majority of other immunotherapy type drugs, however, in that the cells that underpin them (the T cells) are derived from the patient themselves, as opposed to created ex-vivo or donated by another individual.
By way of a quick introduction to the science, the drug is created by removing T cells from the patient and modifying it to recognize cancerous cells. Generally, this involves teaching them to recognize a particular antigen that’s expressed by the cancer cell in question. The CAR element of the CAT-T name stands for Chimeric Antigen Receptor, and refers to the receptor that is basically added to the T cell, which is what recognizes the antigen.
So, the T cell is reintroduced to the body (having been modified to recognize an antigen specific to the cancerous cells) and goes on the hunt for any cells expressing the antigen in question. When it finds these cells it links on to them and induces apoptosis, which is a type of cancerous cell death.
In this instance, the antigen that the drug is taught to target id called CD19, and it’s expressed in abundance by cancerous cells associated with this sort of B cell cancer. It’s also not expressed to any real degree by other types of cells, making the therapy (in theory, at least) highly selective to the cancer cells it’s targeting.
The takeaway from this selectivity is that the drug should translate to minimal toxicity and – when compared to things like chemotherapy, which just goes about killing cells all over the place and is, by proxy, highly toxic – should be superior from a tolerability perspective.
So what did the data tell us?
This was an interim analysis, and in patients treated with the drug in the target indication, three-month overall response rate (ORR) was 45%, with 37% complete response (CR), while all patients in CR at three months remained in CR at data cutoff. The best ORR was 59%, with 43% achieving CR.
Certain safety endpoint might be deemed as red flags if they were in any other indication, but in an oncologic indication, the FDA is generally willing to set the bar higher from a safety perspective for a cancer drug because the alternative (SOC, chemo) is highly toxic in itself, and non-treatment results in death.
That’s a primary endpoint meet at interim and, now, all eyes are on study close to see if the company can carry the successful numbers forward through the end of the trial period.
So what’s next?
Well, the top-line data from the study should hit press at some pint before the end of the year; we’re taking this as mid to late fourth quarter, based on the trial’s protocol. Once this data hit’s, Novartis will take stock of the outcome and – if it’s positive – submit a registration application to the FDA in the US and the EMA in Europe consecutively in both regions.
The drug is breakthrough, so this phase II should be enough to underpin an NDA in the above-mentioned regions, assuming the data carries through to completion as strongly indicative of efficacy and relatively safe (so, just a continuation of what we’ve seen in the most recent report.
On to keep an eye on.