RE:Least we under appreciate safety in the 3-4L mTNBC I think risk reward assessment plays a role for drugs targeting unmet conditions so late stage cancer patients with no other options available are in that unmet category.
That’s probably why despite lacklustre safety or efficacy those drugs have a commercial market as the last resort for patients. So that trade off between risks and benefits of the drug is more relevant for serious conditions.
“The newly published draft guidance offers insight on how the FDA considers therapies that may carry significant risks. In cases where that treatment offers clear, meaningful benefits or has clear advantages over currently approved treatments, those benefits may outweigh the risks. In other cases, the FDA may consider subpopulations and determine that the benefits to them outweigh the risk even if the same is not true for the broader population.
According to the draft guidance, the FDA may tolerate greater uncertainty for a therapy for a serious disease with high unmet medical needs, including those that may be going through the accelerated approval pathway.”
https://www.jdsupra.com/legalnews/weighing-benefits-and-risks-new-draft-9225122/
Wino115 wrote: I realize there is no cancer drug with out efficacy, but we should appreciate that we are seeing a level of safety (should it continue) that none of the ADCs have so far been able to achieve for the more advanced patient drugs. This is meaningless unless we see decent efficacy. But I point it out because I think from a commercial and revenue standpoint, it would point to a much wider and quicker adoption. If we get that POC and efficacy, this safety aspect really magnifies the potential revenue share for TH1902.
By way of example, Trodelvy in 3L currently has 34% market share and growing (expected peak revenues of $2bil just for TNBC and $1bil for urothelial) and it has a lot of SAEs >= Grade 3. It's been on the market one year. You can achieve a lot in one year if the data supports superiority along the efficacy/safety tradeoff line. Oncologists will move as a herd if the data presents a clear conclusion, like they have for Trodelvy. Also, it's pretty clear Quality of Life issues will move the needle in these 3L/4L settings with doctors.
As a reminder, things moved fast for Trodelvy between the 1b and 2 trial because it was an unmet need in 3rd Line metastatic TNBC. Analysts pretty quickly put those peak revenue numbers into their modles 4-5 years out.
Here is a quote from a recent cancer KOL event transcript I read:
".... some recently approved ADCs like Trodelvy had a greater than 40% grade 3/4 neutropenia, Padcev, which recently approved has a 17% greater than grade three cutaneous toxicities, and then Zynlonta more recently approved in DLBCL had 10% pleural effusion...
...but the goal (in their trial) will be taking some of the lessons learned, which include holding doses, dose reductions, increasing times between the doses as a better way to manage these toxicities and allow for greater exposure time for the patients.... So the longer we can have exposure, the better off these patients will be in terms of maintaining a better quality of life and also hopefully survive.." (CEO of MacroGenics, Scott Koenig, 10/21)
So far we are at twice the dose of the maximum docetaxol used normally and it's likely 7-8x the chemo is getting in to the tumor cell. And only 1 SAE (admitedly out of maybe 3-6 patients dosed at 340mg or higher) and it is only a Grade 2 SAE. Nice start from what we know.