Seattle Genetics, Inc. (NASDAQ:SGEN) just kicked off a pivotal phase 3 trial in its lead acute myeloid leukemia candidate. There are very few effective treatment options available at present, and so – especially in newly diagnosed patients – this indication is very much subject to an unmet need. As such, if the company can push its candidate through the ongoing pivotal, and garner some decent efficacy results as it does so, it could be exposed to a large potential patient population given an agency green light. With this in mind, and in line with the trial initiation, here’s what we are looking for going forward. As ever, let’s have a quick look at the science behind the drug in question before we get started on what to look for from the trials.
The drug in question is Vadastuximab. From its description, – or at least, that is, the description of its mechanism of action – it might seem pretty complicated, but it’s not, so stick with us. The drug is what’s called an antibody-drug conjugate (ADC). These types of drugs involve an antibody and some active compound stuck together by a binding agent. The antibody carries the active compounds to target cells, attaches to receptors, and releases the active compound to do its work in destroying the cells in question. In this instance, the active compound is what’s called a a pyrrolobenzodiazepine (PBD) dimer. The best way to think of PBD is as a chemotherapy drug, but far more focused due to the selective delivery of the ADC. Chemotherapy is generally systemic (by this, we mean it is equally distributed throughout the bloodstream). The systemic nature of chemotherapy drugs is what causes the commonly associated side effects – nausea, pain etc. It’s also why people become very sick when undergoing chemotherapy – because the drugs don’t target cancer cells specifically, a high toxicity is required. Through the use of drugs like Vadastuximab, development stage oncology companies are hoping to greatly reduce the toxicity of cancer treatment through selective targeting. In this instance, the drug targets a specific type of receptor that is only (or most commonly) associated with amyloid cells – the cancerous cells associated with acute myeloid leukemia. Upon locating this receptor, the antibody connects to and releases the PBD, which attacks and kills cancer cells. At least, that is the theory.
So what are we looking for in the ongoing trial? The trial is a randomized, double-blind study, with centers across the globe. It is investigating the drug in combination with two already approved standard of care acute myeloid leukemia drugs, azacitidine and decitabine, which are currently used primarily to treat older, advanced patients. Half of the study candidates will receive one of these two aforementioned drugs plus Seattle Genetics’ candidate, and the other half will receive one of the two already approved drugs and a placebo. Primary endpoint is a statistically significant extension of overall survival in the active study arm, when compared to the placebo arm. In this instance, it’s a pretty simple trial – if the study arm is shown to extend survival, the drug works. Secondary endpoints are pretty extensive, but include remission rates (by way of a comparison between the two arms) and 60 day and 90 day survival rates. While these won’t be as important when it comes to final analysis as the primary endpoint, they could play a key role in the FDA’s decision come PDUFA – especially if safety and tolerability is in line with (or worse than) current standard of care.
Data from previous trials in frontline versions of this indication suggest an advantage in combining the company’s candidate with the current standard of care treatments, but the impact of the combination in elderly patients (which this phase 3 study is focusing on) is not yet known. So what are the near term milestones? Well, the company expects interim data before the end of the year, so we will be looking to this interim to gain insight into the safety profile and efficacy profile of the drug when used in combination with the above-mentioned treatments. Completion is expected by May, 2019, and final evaluation should come just a month later. A long haul, but one to keep in mind going forward.