SGEN put up good numbers for urothelial CA:https://www.fiercebiotech.com/biotech/asco-astellas-seattle-... Astellas and Seattle Genetics unveiled data showing their antibody-drug conjugate shrank 44% of tumors and eliminated 12% of them in patients with advanced urothelial cancer. The treatment, enfortumab vedotin, could become an option for patients whose cancer has worsened despite receiving chemotherapy and checkpoint inhibitors.The phase 2 data, presented Monday at the annual meeting of the American Society of Clinical Oncology (ASCO), come from 125 patients with urothelial cancer that has spread locally or metastasized elsewhere in the body. This cancer primarily occurs in the bladder, but it can also affect the urethra, kidneys and other organs in that part of the body. These patients are generally first treated with platinum chemotherapy. ...Siegall said the waterfall plot of the data showed 84% of the patients saw some reduction in tumor size. Enfortumab also helped patients live a median 7.6 months longer and kept cancer at bay for about six months. The response rate was steady across patient subgroups, including those for whom PD-1/PD-L1 blockers did not work, those with liver metastases and those who had received three or more prior treatments. compared to urogen:https://investors.urogen.com/news-releases/news-release-deta... UroGen Pharma Ltd. (Nasdaq: URGN), a clinical-stage biopharmaceutical company developing treatments to address unmet needs in the field of urology, today announced findings from a secondary analysis from the pivotal Phase 3 OLYMPUS trial which showed that UGN-101 (mitomycin gel) for instillation, an investigational mitomycin formulation, demonstrated a 59 percent complete response rate in a subset of patients with endoscopically unresectable low-grade upper tract urothelial cancer (UTUC). Findings were presented by Seth Paul Lerner, M.D., FACS, Professor of Urology at Baylor College of Medicine, in an oral presentation during the plenary session at the 114thAmerican Urological Association (AUA) Annual Meeting in Chicago.The analysis showed that in the OLYMPUS intent-to-treat population, 71 patients had undergone PDE at the time of the analysis and 42 of the 71 patients (59 percent) achieved a CR. Forty-one patients entered follow-up. Of the evaluated complete responses to date, 27 patients have undergone a six-month evaluation, and 24 out of 27 patients (89 percent) have remained disease free at six months. Overall, 5 of 41 patients who achieved a CR have relapsed at any time during the study. there are problems that both of these are single arm trials. Onto the good about Urogen:78% of pts undergo nephrectomy with low grade upper tract urothelial carcinoma (LG UTUC); UGN-101 aims to reduce this. TAM of 6-8k.-UGN-102, which to me seems like the same drug but packaged differently (?), aims at low-grade non-muscle invasive bladder cancer, ~40k new cases / yr, and "intermediate risk" =10-20% of that (say, 4-8k TAM)if treatment is priced at 50k/ yr, at 6k TAM, thats 300m; double it for UGN-102 (another say 6k patients @ 50k/yr, so a total TAM somewhere, ballpark, between 500-750m.Urogen's market cap is 750m right now. My downside: These are for two separate indications, but I question if SGEN may take the bulk of business for "intermediate" cancer. Not that it's necessarily a better treatment, but because I think its a paradigm shift to treat this in the urology office and market penetration, especially for a new company, may be tough. With that said, if someone like Jannsen, whom urogen has (had?) a partnership with for another drug using a similar delivery system, comes and scoops them up, they may be able to expand their footprint a bit faster. at 4-5x peak sales, thats 2b+ disclosure: Cosmid may have talked me into a starter position in this, if for no other reason than to watch the story unfold (that, and, well, we've hit on some many other biotechs in the last 2 years I've lost count- I think we're on 7? 8?), but single arm trials that require a paradigm change amongst clinicians scare me a bit.
Cosmid may have talked me into a starter position in this, if for no other reason than to watch the story unfold (that, and, well, we've hit on some many other biotechs in the last 2 years I've lost count- I think we're on 7? 8?), but single arm trials that require a paradigm change amongst clinicians scare me a bit. Another option for you Fuma, is to watch me suffer while my position in URGN is underwater ;-) I'm not worried about single arm study for URGN. It is simply repackaged mitomycin C that is in a novel matrix that forms a gel at body temperature while a fluid at room temp. Sort of counter-intuitive, but it works. Currenly, mitoC is delivered by instillation into the bladder, held for a fixed period of time, and then emptied via cath. The gel is "painted" onto the tumor and remains in place on the bladder or ureter wall until the drug is delivered over days rather than hours. Instillation of MitoC doesn't work for the renal pelvis and you don't want reflux into the kidney itself. Access to the renal pelvis is very limited by transurethral instruments, so if approved, this would allow painting the tumor via transurethral approach and avoiding neprhrectomy. So single arm doesn't bother me because there are years of history behind use of MitoC instillation. Also, it is hard for me to imagine that prior FDA meetings did not address this given it has received breakthrough designation. The folks I talk to don't like doing neprhectomy in the first place for low-grade cancers. Right now, it is a necessary evil, and the paradigm doesn't change that much. I also don't think that SGENs drug overlaps at all with URGN approach. One is for local, the other distant disease. I think URGN will have a PDUFA date long before SGEN finishes P3. Cosmid (long URGN)
Also, it is hard for me to imagine that prior FDA meetings did not address this given it has received breakthrough designation. Oh, well THAT'S reassuring! 🤣🤣🤣https://jamanetwork.com/journals/jamainternalmedicine/articl...Surely you've seen this gem which places some egg on the FDA?"Of (accelerated approvals), 6 (21%) approvals showed overall survival benefit," Yikes. Not totally apples to apples, but faster without solid trials doesn't make an open & shut efficacy case post approval! But hey, we still give placebo but with more bleeding for strokes (tpa); so what do I know... 🤷???
Good one Fuma. Not my best effort. The truth is the risk/benefit of MitoC has never really been clearly defined in this setting. It is a mutagen, so it is not without risk however it is delivered. That said, the comparison is really about the gel versus nephrectomy. I also have reservations about the absolute risk of superficial bladder ca that has low malignant potential (Grail and GH can figure that one out; same concept of liquid bx, but you have to pee). But what is known is that most, if not all, start with a pre-malignant superficial lesion, and designing a trial with a control arm like placebo, or sham nephrectomy, isn't going to happen. The outcomes with nephrectomy are great. Especially if you don't mind losing a kidney. ;-)UGN-201 will undoubtedly have a control arm; namely, BCG. It is after all, and attempt to mimic the toll-like receptor 7 signalling with hopefully fewer nasty side-effects. I don't see this is a high reward stock, so my advice to the skeptical would be to stay away. To some extent it is not about $, it's about it being contrarian with biotechs. I think you know by now that I love going against the grain.Cosmid
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