RE:RE:RE:RE:The FDA might have no choice... Eoganacht wrote:
"Hi wildbird1 - If TLD1433 is approved for the treatment of BCG-unresponsive NMIBC doctors will have some discretion in using it "off-label", especially if it continues to exhibit such a superior safety profile. Roswell Park doctors do this regularly, treating all sorts of cancers with pdc's for cancers they were not approved for by the FDA.
"FDA regulations allow doctors to prescribe medications off-label, and sometimes the medications’ effectiveness for an off-label use can lead to FDA approval for that new use......
.....Roswell Park physicians sometimes offer patients off-label use of Photofrin, one type of photosensitizer used in PDT, for treatment of such diseases as oral cancer. While Photofrin is not FDA-approved for oral cancer, is has been shown to be effective for that use."
Diseases We Treat With PDT at Roswell Park
So it may be possible to treat NMIBC with TLD1433 instead of BCG without another trial, but first TLD1433must be approved as a treatment for BCG unresponsive NMIBC. I think you're right that that 7-10 year waiting list will be a pretty strong motivation for doctors to try TLD1433 as a replacement for BCG if it displays great efficacy and safety in BCG-unresponsive NMIBC.
I think it's deceptive the way drug companies have been reporting the results of their NMIBC trials. TheImmunityBio press release made it impossible to figure out what the CR rate at 12 months was. I had to go to the Journal of Clinical Oncology to find it - where it was revealed that the 12 month CR rate was 42%
https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.6_suppl.510
The ImmunityBio press release did give a clue that the 24 month CR rate was somewhere between 30%-40% when they made this statement:
"The latest data from this trial exceeds AUA-FDA workshop benchmarks for both the magnitude of complete remission and the duration of complete response for new therapies for BCG-unresponsive bladder cancer. Indeed, the benchmark of 30% durable response at 18 to 24 months for a clinically meaningful therapy "is likely too high and may not be realistically achievable,"3 according to recommendations published in the Journal of Clinical Oncology. This "realistically unachievable" endpoint of 30% durable response at 18 months has in fact now been achieved and exceeded with the combination of Anktiva and BCG in this trial reported today."
Suppose 70 out of 100 patients - 70% of our phase 2 trial patients achieve a CR at any time. Suppose 60 patients - 60% are still CR at 12 months. Then one would expect Theralase to report that 60% achieved a CR at 12 months.
But if Theralase reported results the way Merck and ImmunityBio have been doing, they would report that 86% achieved a CR at 12 months!
The 86% is just the percentage of the 70 initial CR patients that were still CR at 12 months."
Off for a couple of days & see a lot of great posts...keep them coming : ).
The off-label use is a great point & one I've mentioned a few times. I see the potential for off-label use being particularly high within the field of oncology, especially in those cases of refractory cancers with few approved treatment options. When it comes to life & death decisions, oncologists & patients often find themselves more than willing to try off-label treatments if there is any chance for a better outcome. And if/once TLT's ACT is found to work against more than one tumor type (I.e. NSCLC, GBM), I'd expect not only more off-label use as a primary treatment for NMIBC CIS patients who are BCG-naive (especially considering the BCG supply shortages), but also more off-label use as a combo/adjuvant or stand-alone option for many other tumor types. If our ACT is approved, I also imagine uro-oncologists over time may offer more treatments &/or our ACT with a shorter interval between treatments for the more resistant cases (i.e. offer an earlier treatment to the partial or non-responders soon after the 90 day assessment). If approved, this ACT will evolve in the clinic, & there will likely be multiple medical iterations depending on tumor type & patient needs...that is the art of medicine, & fortunately, this aspect is not regulated & should never be. All imo.
In the case of BCG-unresponsive NMIBC, radical cystectomy/bladder removal is simply not an option for many patients. Unfortunately, the two currently approved FDA treatments offer little comfort/reassurance. Historically, Keytruda & Valrubicin provided a modest 41% CR at any time/19% CR at 12 months & a meager 18% CR at any time/13% CR at 12 months, respectively. And disease-free survival (no signs/symptoms of cancer) was merely 4% at 2 years in the Valrubicin trial. With those relatively dismal CR %s, certainly a good number of patients imo would rather avoid prolonged pain for little gain & begrudgingly opt in for bladder removal. Better, safer & more patient-friendly options are sorely needed for this unmet indication & so many others...I'm feeling very hopeful that TLT's ACT can fill that void.