From January 16th (sound familiar?) All this was known and even presented last WED at Leerink
So what changed at Wedbush???? This says that an immediate U.S. filing is unlikely BUT
From Life Sciences — Biotechnology (JackBass team)
PH2 NTM DATA PREVIEW: WE SEE A VERY HEALTHY CHANCE OF SUCCESS;
RAISING PRICE TARGET TO $30
Reiterate BUY, raising PT to $30 on Arikace’s increased potential in
nontuberculous mycobacteria (NTM). INSM’s lead drug Arikace is an
inhaled liposomal form of potent, FDA-approved antibiotic amikacin. We
expect positive data from a Ph2 US NTM trial in March. Our higher
pNPV-based $30 target is driven by a higher chance of success.
Based on proprietary analysis/KOL talk, we think INSM’s Ph2/3 NTM
trial has a good chance of success with late March top-line data. The
trial is powered to show a 1-point change on the 7-point semiquantitative
scale of NTM infection burden. We think a 1-point benefit in
these severe trial patients (whose baseline score we think will be ~5)
would correlate with a benefit in QoL and be clinically meaningful.
More confidence on data variance and noise: interim look gives us
comfort on “neatness” of data and powering. INSM conducted an
interim blinded look at the variance of the data to determine if the Ph2
was adequately powered. The look indicated data dispersion/ variance
fell within trial powering assumption. We think it is unlikely INSM was
able to see graphical representation of the data dispersion during
variance calculation, which could have provided a “tell” on data.
Unless we see cures in the Ph2/3, we think immediate US filing is
unlikely, no matter what KOLs agitate FDA for. Based on our KOL
conversations, we think FDA still has a lot to learn about NTM, having
been previously hung up on TB-like “cure” endpoints. Given trial patients
are end of the line, hard to treat, cures with only 3-mo Tx are unlikely.
INSM may decide to focus initial registration on a subset of patients
based on pre-specified stratification (CF; organism) depending on data.
I suspect most investors would agree this was the key comment -
"Unless we see cures in the Ph2/3, we think immediate US filing is unlikely, no matter what KOLs agitate FDA for."
Lewis seemed to have a markedly different opinion last August -
"Analyst - "If you can get approval on the data coming up is it going to be conditional approval? Would you need to do a confirmatory trial? If it's not enough for whatever reason, what would a Phase III trial possibly look like?"
Lewis - "So I think we always want to plan for the need for additional data. And it certainly is worth remembering that in the interests of identifying the best clinical use of the drug additional work is always a prudent thing to plan for.
Having said that - I believe this study will stand on its own, and will be adequate for registration and approval".
"I think anything that shows promise by way of reduction in bacterial density will be enough".
I wonder if that first (JackBass team) reservation that the FDA will not be influenced by key opinion leaders suggests a lack of awareness of the other drivers for accelerated approval -
1. The NIAID suggested the development of Arikace as an NTM therapy, and conducted the clinical trial via their network of study centres.
2. The Cystic Fibrosis Phase III study proved that Arikace delivers amikacin to pseudomonas bacteria in the lungs.
Provided the NTM results at least confirm that the amikacin also reaches mycobacteria in the lungs, approved use of Arikace will reduce the opportunity for drug-resistant strains of bacteria to develop through the treatment of MDR-TB, NTM and Gram-negative pulmonary infections by aminoglycoside injections.
I imagine the FDA could well be influenced by the needs of the NIH, CDC and WHO.
" Unless we see cures in the Ph2/3, we think immediate US filing is unlikely " "INSM may decide to focus initial registration on a subset of patients "
Thank you for that report. What this report is doing is preparing for many possible outcomes,not just the pie in the sky cure but a smaller patient base a different type of trial etc.