Two billion dollars seems spendy for a repackaged chemo agent that has been on the market since 1996. It’s no secret, either; irinotecan is standard of care in colon and lung, though, weirdly, it doesn’t get prescribed a lot in breast (despite the fact that irinotecan targets TOP-1, which is commonly overexpressed in breast).
What Seattle Genetics may be banking on is the branding; this is a “new drug” for triple negative breast cancer, which is great marketing when, in reality, there is no drug that is for TNBC.
IMMU-132 is an opportunity to give patients who only have access to chemo, well, more chemo. This isn’t T-DM1, which was a game-changer because it enabled the targeted delivery of a chemo agent (emtansine) that was too toxic to give on its own. IMMU-132 is more of a Doxil/doxorubicin situation.
For what it’s worth, this strategy did work with Xeloda, which is just oral 5-FU; every breast patient tries Xeloda because it’s oral and the side effects are nonexistent. I’ve never heard of anyone in breast getting IV 5-FU.
Immunomedics loves to talk about the reduction in toxicity, and I only looked quickly, but I haven’t seen numbers on the incidence of neutropenia and diarrhea (common irinotecan side effects) in IMMU-132 versus irinotecan. It seems logical that AEs would be lower, but I would be curious how much lower when irinotecan is tolerable on its own – so tolerable, in fact, that it’s given in a platinum-based triplet in colon (oxaliplatin, irinotecan, 5-FU) and lung (I’ve seen cisplatin, etoposide, irinotecan and cisplatin, docetaxel, irinotecan). You would think these triplets would kill people, but apparently they do not. We can also assume that TNBC patients skew younger and healthier than the colon and lung populations.
Beyond TNBC, which is a small population who would be receiving the drug second- or third-line, Immunomedics seems to be targeting lung and GU cancers, and given that the BLA hasn’t even been submitted yet, I’m not sure when SeaGen is going to see their investment pay off. Is this where we’re going to be in a year? Whether PD-1s will work in TNBC is still a bit of a wildcard, but lung and now bladder are pretty entrenched in PD-1s, and lung patients likely already received irinotecan first-line. Given that TNBC is, on the surface, non-targetable, the indication seems amenable to being penetrated by genomic sequencing. Sequencing is more accepted in lung, but the practice will grow there too. Where does irinotecan, in any form, fit into the personalized model?
Think about the promise of sequencing for a TNBC patient, who has had three or four lines of chemo. She could have an EGFR mutation, which is suddenly targetable with multiple agents that are in a different AE universe from the taxanes and platinum agents she has already received. A targeted therapy could also be the difference between losing your hair and not, which is a bigger deal than you might think (for non-TNBC patients who have more options, this can be the deciding factor in one drug over another). Despite my question above, big picture, you’re not comparing toxicity between IMMU-132 and irinotecan; that model is going away. You’re fighting personalized medicine, which is not where I’d put my money in 2017.
B4 U Consent 
Irinotecan doesn’t target TROP2, it targets topoisomerase.
IMMU-132 is an ADC (antibody drug conjugate) of anti-TROP2 conjugated to the activated metabolite (SN-38) of irinotecan, thereby in theory, more specifically delivering the cytoxin SN-38 to TROP2-expressing tumor cells.
Its not at all like comparing doxil/doxorubicin – rather its just like T-DM1.
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Thank you for taking the time to comment. I botched this. First, the TOP-1 typo is fixed – embarrassing that it was up as long as it was. On the ADC front, I appreciate the criticism and agree that I was unclear. The T-DM1 comparison was poorly drawn, but what I meant to say is what I like about is that it’s more than the sum of its parts; with T-DM1, trastuzumab serves as a targeting mechanism but retains some inhibitory effects of its own, and it’s linked to a cytotoxic with activity that previously couldn’t be effectively delivered. And we’ve seen that pay off in MARIANNE and EMILIA, and we’re sorting a role for it in early-stage BC. It’s something we didn’t have before in solid tumors that may have the potential to cross settings and change the SOC, while liposomal doxorubicin and Xeloda enabled novel, lower-toxicity delivery of doxorubicin and 5-FU, respectively. It’ll be bigger than Adcentris, but I do agree with the general expectation that IMMU-132 is likely to inhabit a third-line space in the metastatic setting and don’t really see it as a game-changer (revisiting this post months later, I’m now pretty excited about what ipatasertib is going to do in TNBC, as well as methods of priming TNBC for immunotherapy). Anyway, my response is considerably less relevant since the SeaGen deal fell apart and we’re still waiting on that BLA decision, but it bothers me that I mangled it on the first take. Thanks for reading and reaching out.
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