My take on the upcoming inflection point.
The positive.
1. They have been predicting mid year '17 for interim analysis since November of '16... with each different conference, earning call, pr... from November through last week, the 'we expect the interim analysis to occur in mid '17.
2. We know from the phase I/II data that tumor growth rate was attenuated with high dose VB-111, it works in animal models, and it worked in a non-selected phase II population which did not have an obvious distinction in patient population(age, sickness, number of progression).
3. It also shows signs of biological activity in the phase I trial, the phase II ovarian and thyroid trials in a number of different ways.
4. While it sounds weird, the feverish patients did better than the non-feverish patients... both in ovarian and also in glioblastoma phase II trials.
5. There are anecdotes of efficacy in the phase III--a CR with VB-111 in a patient who developed fever after each dosing. While this is an anecdote of a single patient on the Inspire thread, it supports the thesis of an immune mechanism in some patients. Recall there were two CR's in the phase II--one non-durable and one durable and ongoing. Interestingly, the major response in the ovarian trial also developed high fever and chills.
6. Biospies in the ovarian trial showing immune infiltration with VB-111 treatment is a tangential support of an immune effect as is the tail in the thyroid cancer patients after several years of therapy.
The negative.
1. Recurrent glioblastoma is HARD. Nothing works, or has ever worked. Avastin does not improve overall survival but does improve progression free survival and various quality of life metrics such as dependence on steroids. The highly promising checkpoint inhibitors which garner billions a year appear--although it is early--to be a dud in Glioblastoma. Might that be because their immune systems are so beat up, or checkpoint inhibitors do not cross the blood brain barrier, or the tumor environment is too hypoxic for anything to take effect... avastin, chemo, or checkpoints in the recurrent setting? Who knows, but we do know that vaccines, various anti-anti-angiogenic compounds, chemo, and probably checkpoints show little efficacy in the recurrent setting(or in the frontline setting).
2. The phase II rGBM trial was not randomized and compared to historical controls. I don't really buy that argument, but clinical trials are riddled with the comparison to historical controls assertion.
3. The phase II rGBM trial showed a random, fluke of an anomaly? Effect size where the phase II shows efficacy which fades in the phase III setting, the continuous group received more avastin? Take your pick. Nothing really makes sense for an explanation as Dr. Chlousey asserted in the KOL last May.
4. Some of the throw away lines by Dror H... at the recent KOL event for their new target... we always worry have we had enough patients and powered the trials to show significance... that's why we do randomized trials line kind of scared me to be honest.
5. Returning to the first negative on the list. Say you invented Avastin or checkpoint inhibitors a few years ago, and decided to pursue a nice orphan indication like rGBM. You would have probably failed to show efficacy in the GLOBE trial to show improved overall survival.... i.e. checkpoints versus chemo or Avastin versus chemo. Think about that for a moment.
I can see good points on either side of the fence here. I'm not selling any and may actually buy a few more thousand shares before the interim, but I wouldn't be surprised by a positive interim finding to move ahead or a negative interim finding where we don't pass futility. On the positive side of the equation, the payoff is huge here, bigger than most here visualize. Because nothing has been approved in the rGBM outside of Avastin(which doesn't improve survival odds), a green light on the interim leading to positive separation of the curves at trials' end and FDA approval will be a watershed moment in the treatment of glioblastoma. I see failure with the price crashing to 1-2, but a seismic move upward with FDA approval. All IMHO.
