I received a DM from a board member—who I will keep anonymous— who responded to my last post about the possibility of starting patients on the 350 dose and escalating as needed. He/She stated the following:
“and no, the FDA is never going to support a convoluted start at 350 regimen. they'll want ONE optimal dose and that's that. regardless trying to prove out the particulars to such a concept would be an absolute nightmare. JL makes plenty of mistakes but he would never make that one.”
If you take seriously the idea that the medical establishment is moving towards “precision medicine,” then I think you are dead wrong. And missing the importance of the Signaterra ctDNA assay to provide molecular response data that will tell oncologists exactly when they need to up the dose. It’s not convoluted at all—if the numbers are going down significantly, keep them on the 350 dose. If the numbers plateau or rise, move them up to the 700 dose. It is pretty simple, actually. They will have to find the appropriate numbers to guide them… but that is the incredible value of the Natera alliance (both for documenting the ctDNA numbers of individual patients and providing those 2 million data points for comparison). Similar to how CPS numbers guide oncologists on whether or not to administer an ICI.
The DM also included this comment:
“the good 350 response is probably going to lead to the FDA asking to see 525 in the next trial… if the FDA wants a 525 / 700 p2, then years are added to the crc development.”
That is a more cogent observation. If the FDA wants to see 525 data, they will get it. Most likely it will come from our partner, who will have to deal with that particular question. But given the safety record of leronlimab, and let’s say a 25/35% ORR and 85% DCR and double the OS on one of the two doses—you really think the FDA is gonna hold up some kind of expedited access for MSS mCRC patients with no better options? I don’t think cancer patients—not to mention their advocates and loved ones—would stand for that. And if prime and pair works for MSS CRC, and the FDA says—well, we’ve got to see 525—the political cost for holding up access would be incalculable. There would be riots in doctor’s offices. These days, people would bring guns.
And don’t forget—Europe is still in play. If our partner is European we might be approved in the EU before in the US… if the FDA becomes a hard ass about 525.
It really looks like the FDA is trying to expedite life-saving drugs for un-met needs in large patient populations. Historically I’d say—I’ll believe it when I see it. But the combination of financial self-interest leading to a BP partnership, saving and extending the lives of lots and lots of patients, and a spotless safety record makes me believe we’ll actually see some sort of “expedited access” sooner than later. I am pretty ignorant about the details of Accelerated Approval and Vouchers and Breakthrough Therapy Designation, so I’m not going to offer up any timelines or approval dates. (I do follow what is said on the board, but I don’t have any insight into the pace of the FDA bureaucracy or their inner workings). The science and the social implications are what gets me out of bed in the morning. And I think both the science and the social implications of leronlimab—it’s utility in cancer—are going to shake up business-as-usual. Even at the FDA! How that plays out, well, if the trial results meet expectations, it is going to put tremendous political pressure on the FDA. I’ll leave it at that.
“and no, the FDA is never going to support a convoluted start at 350 regimen. they'll want ONE optimal dose and that's that. regardless trying to prove out the particulars to such a concept would be an absolute nightmare. JL makes plenty of mistakes but he would never make that one.”
If you take seriously the idea that the medical establishment is moving towards “precision medicine,” then I think you are dead wrong. And missing the importance of the Signaterra ctDNA assay to provide molecular response data that will tell oncologists exactly when they need to up the dose. It’s not convoluted at all—if the numbers are going down significantly, keep them on the 350 dose. If the numbers plateau or rise, move them up to the 700 dose. It is pretty simple, actually. They will have to find the appropriate numbers to guide them… but that is the incredible value of the Natera alliance (both for documenting the ctDNA numbers of individual patients and providing those 2 million data points for comparison). Similar to how CPS numbers guide oncologists on whether or not to administer an ICI.
The DM also included this comment:
“the good 350 response is probably going to lead to the FDA asking to see 525 in the next trial… if the FDA wants a 525 / 700 p2, then years are added to the crc development.”
That is a more cogent observation. If the FDA wants to see 525 data, they will get it. Most likely it will come from our partner, who will have to deal with that particular question. But given the safety record of leronlimab, and let’s say a 25/35% ORR and 85% DCR and double the OS on one of the two doses—you really think the FDA is gonna hold up some kind of expedited access for MSS mCRC patients with no better options? I don’t think cancer patients—not to mention their advocates and loved ones—would stand for that. And if prime and pair works for MSS CRC, and the FDA says—well, we’ve got to see 525—the political cost for holding up access would be incalculable. There would be riots in doctor’s offices. These days, people would bring guns.
And don’t forget—Europe is still in play. If our partner is European we might be approved in the EU before in the US… if the FDA becomes a hard ass about 525.
It really looks like the FDA is trying to expedite life-saving drugs for un-met needs in large patient populations. Historically I’d say—I’ll believe it when I see it. But the combination of financial self-interest leading to a BP partnership, saving and extending the lives of lots and lots of patients, and a spotless safety record makes me believe we’ll actually see some sort of “expedited access” sooner than later. I am pretty ignorant about the details of Accelerated Approval and Vouchers and Breakthrough Therapy Designation, so I’m not going to offer up any timelines or approval dates. (I do follow what is said on the board, but I don’t have any insight into the pace of the FDA bureaucracy or their inner workings). The science and the social implications are what gets me out of bed in the morning. And I think both the science and the social implications of leronlimab—it’s utility in cancer—are going to shake up business-as-usual. Even at the FDA! How that plays out, well, if the trial results meet expectations, it is going to put tremendous political pressure on the FDA. I’ll leave it at that.
