Decide for yourselves the odds of Phase III success
The colour I offered on the likely effect on the share price of accumulation triggered by good Phase III data will be meaningless if Arikace fails the ongoing Phase III clinical trial.
Terry tells us that the odds of success are about 50/50. But Terry tells us a lot of things, and very rarely is what he tells us supported by the facts.
Going by the chart in the Company's Phase II extension study presentation, the change in FEV-1 28 days after the third treatment phase - averaged across the 43 patients, and relative to their readings at the start of the study - appears to have been an increase of about 5%.
This doesn't provide 'apples for apples' data for predicting the likely improvement in FEV-1 at the key point in the ongoing EU pivotal clinical trial, as the off-therapy periods in that older study were for 56 days (as opposed to the ongoing 28 days). But it's tempting to assume that the 5% increase would likely have been higher had the two earlier off-therapy periods been for only 28 days.
There is however 'apples for apples' data available for Tobi, the drug with which Arikace is being compared in the ongoing clinical trial. It was generated in a study of Gilead's Cayston where Tobi was once again the comparator therapy -
"Patients receiving Cayston had an adjusted mean actual increase from baseline to six months in FEV-1 percent predicted (averaged across three treatment cycles) of 2.05 percent compared to a 0.66 percent decrease for those receiving TIS".
As with the ongoing Arikace clinical trial, that Cayston study entailed three cycles of 28 days on therapy / 28 days off therapy. But it's important to note that the key efficacy metric here was the AVERAGE change in FEV-1 throughout the study period. Both Cayston and Tobi evidenced significantly greater efficacy in the early stages of the study compared with that evidenced at the end of the study (the point at which efficacy will be measured in the ongoing clinical trial).
The actual 'apples for apples' data - the change in FEV-1 at the end of the third 28-day off-treatment period for the approx 130 participants on Tobi - seems to have ranged from a 1% decrease to a 5% decrease - i.e. lung function on average at that point in the study for the patients on Tobi was actually significantly worse than it was at the start of the study.
For there to be any real danger of Arikace failing the ongoing EU pivotal clinical trial Tobi would have to turn back the clock, and deliver the sort of efficacy which supported its FDA approval fifteen years ago - when there was far less tobramycin resistance than has since developed as a result of widespread use of Tobi as a monotherapy.
But the most recent study data available predict an improvement in lung function of 5% or better for the patients on Arikace versus a deterioration in lung function for the patients on Tobi. And all Arikace is required to do in this study is to be not worse than Tobi.
I guarantee you will not see a single reasonable counter-argument from any of Terry's ids.
Having seen the following from rehdvm over the weekend -
"Improved FEV-1 and the probability that Arikace is going to kill lots of different bacteria. Not just Pa. My real hope is for NTM."
- it seems there is serious misunderstanding regarding the potential use of Arikace in controlling the various target pathogens.
One of the leading pulmonologists who attended the FDA-sponsored workshop last year which addressed the development of therapies for Non-CF bronchiectasis observed that around a third of these patients are infected with pseudomonas, as opposed to only seven or eight percent with NTM.
And Insmed quotes -
1. an estimated 50,000 in the US with NTM, with no approved treatments available.
2. more than 250,000 in the US with non-CF bronchiectasis in 2008, with no approved antibiotics - and 30% of non-CF bronchiectasis patients are infected with pseudomonas.
Apart from the obvious implication that rehdvm should invest in a calculator, the crucial factor he is overlooking here is that NTM infection is not thought to be contagious, whereas pseudomonas most certainly is.
I've yet to see an article about hospital-acquired or community-acquired pneumonia which doesn't mention pseudomonas - and it is one of the four gram-negative pathogens named in the new legislation as posing a serious threat to public health.
Hence my optimism that the FDA will approve Arikace as a therapy for all pulmonary pseudomonas infection. There seems little to be gained in approving it for the CF patient population alone if the pathogen is allowed to continue to spread in the non-CF bronchiectasis population. The latter is estimated to be at least eight times larger, and with FDA-approved access only to injected antibiotics it is surely an ideal environment for the development of drug-resistant strains.
Btw - NTM may not be contagious, but Mycobacterium Tuberculosis is indeed contagious. There are inexpensive drugs available to treat routine TB infection, but the nasty side effects have seen the development of drug-resistant strains following poor compliance with the therapeutic regimen. In the recommended therapeutic regimen for multi-drug-resistant TB an injected aminoglycoside is at the top of the list.
Perhaps far more significant is that two billion people worldwide are estimated to be carrying latent TB infection. It's difficult to see the pathogen being eradicated without the use of drugs which don't have the nasty side effects associated with drugs delivered via the bloodstream.
The implications for a liposomal inhalation therapy in are obvious.
Btw - if anybody here thinks Rehdvm's opinion is of any value, why don't you ask him why he sees more value in the potential use of Arikace as a therapy for NTM infection than as a therapy for either Pseudomonas infection or Mycobacterium Tuberculosis infection (latent or active).