I like your numbers. That's about where I am for those scenarios. When we were at 11-12 I felt that a continuation of the Act IV would be seen as a disappointment and drive the price to where we are now. So perhaps no longer much if any downside except in the event of futility.
Possible early stop for efficacy in Q2. Possible. If I'm right, there is no futility assessment, so the news we will get will be either to continue to planned final analysis (Maybe in Q4?) or stop early for efficacy. If we are all fortunate enough to see METIV stopped early, the would be a major catalyst.
In addition, I expect that in the AACR/ASCO period this spring there will be some smaller data presentations on various drug candidates.
You already got an extension-Yahoo screwed up my previous two attempts to post this sentiment several hours ago.
The Glaxo programs are the weakest for OMED as far as the economics go. Less than 10% of the economics of all the partnerships combined. A loss of 45% of market cap is not justified.
I agree with these points. Non-inferiority is a valid endpoint because the result includes reduced side-effects (in this case some serious adverse effects). The reduction or elimination of steroids and their severe downside makes this non-inferior result one that is in fact superior.
There is a history of confusion with the ChemoCentryx approach. Some people had struggles with CCX140. Many did not catch on that even the preliminary (12 Week) results showed a real treatment effect. Even though there was no statistical significance at that point, if you looked at the severe patients (uACR over 800), there were reductions of 29% and 42% seen in the two treatment groups. At that time some thought there was a "platform problem". I think we can now see that that isn't the case at all.
I remember one analyst's question on the CC for the successful 52-week CCX140 data. If I'm correct, he was concerned that, because the drug precisely targets macrophages, there might be immunosuppressive side-effects. Of course, it was explained to him that the whole idea is that by targeting specific macrophages, CCX140 actually avoids the downside of global immunosuppression.
That's an improvement 1.3 months in PFS, not Survival (OS). Although it's difficult to estimate Overall Survival improvements, a ~1.3 month improvement in PFS could conceivably translate to 3-4 months improvement in OS. Many caveats with that, since comparisons with other drugs and indications are complicated. But it is not unreasonable to suggest that's what we might see. Just speculation until we get the full data. I hope we don't have to wait until ASCO (June).
Array positive trial paves way for 2016 approval, says Piper Jaffray
Piper Jaffray analyst Edward Tenthoff says binimetinib meeting the primary endpoint today in a Phase III trial paves the way for Array BioPharma's first approval in 2016. Binimetinib would be the first targeted therapy for NRAS mutant melanoma patients with projected U.S. sales of $166M in 2020, Tenthoff tells investors in a research note. He reiterates an Overweight rating on Array with a $14 price target.
Meg Tirrel spent a few minutes on the Adcom topic. A quick but reasonably thorough and accurate representation of recent events. She concluded with "Folks are definitely more hopeful for Sarepta's drug".
Or simply a new trial with 12 months of therapy on two arms: iSonep 4.0 mg + anti-VEGF compared to anti-VEGF alone. A safe and seemingly effective dose of iSonep compared to standard of care. A duration long enough to (hopefully) expose a treatment effect.
As far as the post-4 months anti-VEGF issue; in clinical trials, after exiting the study, patients will often go back to standard of care or even to other trials. This can be confounding. In this case many patients were "retreated". However, I agree that the argument in favor of iSonep is intact. You see continued lesion size decreases and evidence of longer-term stabilization of VA only in the arms where patients have seen iSonep. You do not see that benefit where anti-VEGF therapy was used alone. The usual question might be whether the follow-on treatments were imbalanced between arms. They did not appear to be to any meaningful degree. Although in this case that might even be expected if any patients already on anti-VEGF therapy and showing loss of VA are not "retreated" due to futility. I don't know the practice well enough to do more than speculate on that.
I've been wondering if and when some of the billions in private money floating around out there might be leveraged to fund or purchase under-the-radar but viable technologies/companies. I'm glad to see that happen. For several years Shkreli has been doing things that, to put it very mildly, strain the limits of good taste. So it's ironic that he is the first example (that I'm aware of) of something that I would like to see a lot more of.
Private money could fund and buy a stake in Lpath- boosting the price significantly. Even if they invested at much higher levels (say, $1 a share), they could still turn around and make %500 (or something like that) a few years down the road.
There's a big place for this kind of thing in the bio space.
With cancer stem-cells, theoretically you can eliminate them and they won't come back, so therapy could be withdrawn and remission would continue. I don't want to over-talk my own analogy, but I just want to emphasize that resolving the underlying pathology would allow for stopping treatment and achieving a durable response or benefit. Inflammatory mechanisms are another example where, when you dial-down a pathology, you achieve a sustained benefit even after withdrawal of therapy.
That's not to say that after further time without iSonep, lesions would not grow and BCVA stabilization would not be lost. There's no way to know that. But these data are at least evidence that iSonep improves the underlying pathology, or at least targets mechanisms such that it has a similar effect. Given the chance, even normal healing may take over, resulting in some of the continued benefit seen.
Just considering this empirically, the apparent benefit is sustained. I would note that for 7 straight months lesion area declined on iSonep alone. For 5 straight months after the last iSonep injection, lesion area declined notably. Each time-point was lower than the preceding one. There is an analysis that can be done (help from a statistician would be welcome here) to determine the probability of each successive point in a data set being higher or lower randomly. While I don't know the answer, I suspect that the probability of 7 successive points randomly moving in the same direction is very low. Also, the sample size from which the data points were generated is respectable. So the data are telling us to seriously consider that the trend reflects something real.
I just wanted to flesh out my points. I think we're largely in agreement. I think we would agree in not wanting to over-interpret the data, and that more analysis is needed. I also think we agree that these results clearly justify Lpath's decision to take iSonep out of the trash bin and put it back on the table.
I agree, Left-e. I was very pleased with the data. I will reiterate from my earlier post and call the results compelling. The data showed potential sustained benefit and superior lesion resolution with iSonep treatment. What is measured clinically is often a down-stream effect of a disease. So a delay or lag in improvement following treatment may be exactly what we should expect if the underlying pathology is resolved by a treatment. An analogy would be anti-EphA3 treatment targeting cancer stem-cells, where leukemia and MDS responses to treatment many take 4 or 5 months but are meaningful when they occur. Upstream resolution results in a delayed downstream effect. (the downstream effect being what is often actually measured clinically) Biology and medicine are full of examples.
It's tragic, because a trial with a primary endpoint at 9 months would have been a success, exposing a real treatment benefit. There were at the time good and sufficient reasons for designing a 120 day trial, so I'm not saying "they should have known better". But I do think it's important to treat a phase 2 as a learning study. Gather as much information as you can and data mine the heck out of it. That's what was ultimately done here and I think with a good result. However, for the purposes of a business decision it was treated as a pivotal trial with rigid endpoints, and decisions were made without the benefit of extensive and long-term data analysis (and yes, Pfizer did have a contractual deadline). So now, we are where we are.
I've seen much lesser drugs and platforms get a second chance. I'd like to see that happen here.
A couple of hours later OCRX will present at Stifel. Presumably there will be something useful regarding the various AASLD presentations.
I believe the initial Phase 2 ALF data will be presented today at 11:45. I would think a PR would coincide with that.
The presentation is actually compelling. The data are consistent with a model where the underlying disease process is alleviated by the action of iSonep. Over time, the downstream pathologies are resolved as the treatment effect of other drugs or even the healing process itself catches up. The elements supportive of this are as follows: 1) The delayed effect in the iSonep-only arm in lesion reduction. 2) The continuous reduction in lesion size for iSonep compared to a plateau seen with anti-VEGF therapy only (the combinations are intermediate in performance over the long-term, also consistent); and 3) The sustained benefit in BCVA seen when iSonep is added to anti-VEGF therapy.
This is just a simple hypothesis which the data are consistent with. My experience in the Ophthalmology space is limited, so I would welcome comments.