Those here who are relatively new to Insmed might benefit from considering the possible implications for this investment of the groundbreaking legislation Obama signed into law in July.
S.3187 included provisions aimed at shortening the approval process for therapies targeting serious unmet medical need, encouraging the FDA to approve drugs at a stage where there is less proof of efficacy than has historically been demanded. The FDA was also given the power to withdraw approval if post-approval studies don't generate the promised level of efficacy.
One wonders if we might see a double whammy here, assuming the analysis due to start this month of the data from that final safety study doesn't throw up any surprises -
1. The results due mid-year from the Cystic Fibrosis EU clinical trial replicate the unprecedented level of efficacy seen at Phase II.
The FDA approves Arikace as a therapy for (all) pulmonary pseudomonas infection, taking the view that if Arikace is effective against pseudomonas infection in people with Cystic Fibrosis it should be effective against pseudomonas infection in people with Non-CF bronchiectasis (an estimated 80,000 patients in the US alone).
Insmed is required to conduct a post-approval study in non-CF patients infected with pseudomonas.
2. The results due around year-end from the NTM clinical trial evidence a compelling level of efficacy.
The FDA approves Arikace as a therapy for (all) drug-resistant pulmonary mycobacterial infection, taking the view that if Arikace is effective against drug-resistant NTM infection it should be effective against drug-resistant TB.
Insmed is required to conduct a post-approval study in patients diagnosed with drug-resistant mycobacterial infections other than Mycobacterium avium complex or Mycobacterium abscessus (including Mycobacterium tuberculosis).
Another key factor for newbies to take on board is the manner in which the efficacy profile of Arikace from the point of view of the FDA is likely to be fundamentally different to that of the average drug candidate in clinical development.
Usually the FDA is looking for proof that an antibiotic kills bacteria (or inhibits the growth of bacteria). With Arikace the FDA is primarily looking for proof that a delivery vehicle works.
If Arikace can achieve an effective concentration of antibiotic in the lungs far more quickly that is possible with any antibiotic currently available, that alone will be a massive breakthrough.
If Arikace can achieve an effective concentration of antibiotic in the lungs far more safely that is possible with any antibiotic currently available, that alone will be a massive breakthrough.
If Arikace can do both .....
Doubtless the idea that the FDA might approve Arikace as a therapy for all pseudomonas lung infection on the strength of data from the ongoing Cystic Fibrosis EU clinical trial seems overly optimistic to many Longs. But I will be disappointed if that happens. If a horse can jump a six-foot wall it can be expected to jump a four-foot wall.
If the Arikace liposomes can deliver their amikacin cargo with a level of efficacy sufficient to kill bacteria which are better protected than most by virtue of being diderm, and have the additional advantage of lurking behind a protective barrier of biofilm, which itself has the additional protection of the thick layer of accumulated mucus associated with Cystic Fibrosis, Arikace can be expected to be effective against any pulmonary bacterial infection for which the cargo is already approved by the FDA.
If both the safety and efficacy data are as expected, and the FDA takes the current amikacin label as a starting point, and removes indications which are not specific to the lung, we'll see something like this -
"Arikace is indicated in the treatment of pneumonia due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, Klebsiella-Enterobacter-Serratia species and Acinetobacter species."
For the sake of clarity - my label suggestion was intended foremost to underline the argument that the FDA (if the study data is good) should approve Arikace for all pulmonary use for which the amikacin it carries is currently approved.
But most here are expecting a MINIMUM approval for a use which isn't even covered by the suggested label, the use of Arikace as a (permanent) maintenance therapy in people with CF. Something along the lines of -
"The improvement of respiratory symptoms in people with Cystic Fibrosis with a history of chronic infection with Pseudomonas aeruginosa".
Although there is obviously scope here as well for the FDA to issue a broader label in the spirit of its new mandate to hasten the availability of breakthrough therapies, with something as broad as -
"The improvement of respiratory symptoms in people with a history of chronic pulmonary bacterial infection"
- (with the condition that Insmed runs the appropriate post-approval studies) it's worth noting that the FDA will assign greater relevance to the risk of lipid accumulation when approving a long-term use of Arikace as opposed to its use in treating pneumonia.
Btw - please bear in mind when reading anything I post that I am in no way any more qualified than the vast majority who use this forum. I seek primarily to encourage others to open their minds to what may be possible.
Your delusion of a fast approval process a ground breaking therapy and uses for everything is far removed from reality. ... like TB!
"I'm currently in discussion with the global Stop TB Partnership, advising them how they should redesign their various therapeutic regimens now that Arikace is available.
When they've finally grasped what they should be doing I'll get in touch with Insmed and give them the benefit of my advice."