There’s also no way of guaranteeing that the company will qualify for the special protocol, though companies developing similar medications have in the past, including CytRx Corporation (NASDAQ:CYTR) which is in the thick of Phase III trials for its own less toxic version of doxorubicin called aldoxorubicin. If it doesn’t qualify, it’s looking at a Phase II and a Phase III pivotal before it can submit for commercialization. And even if it does qualify, CytRx for example has proceeded to Phase III even with an SPA, so there’s no guarantee that commercialization proceeds after Phase II. Nonetheless, an SPA will still likely shorten the development pathway somewhat, Phase III or not.
There’s also the question as to why would a previous developer halt development? In some of the promotional material that Moleculin is distributing, and at its website, the company states:
“30% OF PATIENTS WHO HAD FAILED AN AVERAGE OF FIVE PREVIOUS INDUCTION THERAPIES OF 7+3, RESPONDED TO ANNAMYCIN WELL ENOUGH TO
QUALIFY FOR A CURATIVE BONE MARROW TRANSPLANT…”
This is a bit misleading. Yes, three out of ten patients that took Annamycin reduced their levels of cancerous cells to a level that is acceptable for bone marrow transplants. Only one of these transplants actually happened and was a success, however. The other two died of what’s called tumor lysis syndrome caused by the Annamycin itself, a complication of chemotherapy where too much of a tumor is killed too quickly, overloading the body’s ability to deal with the debris. The deaths, as unfortunate as they are, were still a sign that Annamycin works. It’s just that in its current form it may be too powerful, and tweaking that could take some time. Even if a drug is technically effective, the FDA will probably not approve it if there is a high chance of directly causing death, and that is what investors need to have in mind in this case.
That aside, and even ignoring the fact that 30% isn’t that great of an efficacy rate, the primary endpoint of any pivotal would have to be a reduction towards baseline eligibility for a bone marrow transplant, or there’s no real point in the treatment. Additionally, annamycin doesn’t look that safe so far, at least by FDA standards. There’s a link to the phase I/II in question’s adverse event report here. In the dose determinant element of the trial, which preceded the phase IIa detailed above, Luekopenia, Neutropenia, infection, tumor lysis, pneumonia all cropped up at various rates and grades, and that’s just naming a few.
It’s going to be a while before Annamycin officially returns to the development process, and if it does, previous data has shown its safety profile to be somewhat worrying. Reduced cardiotoxicity, or even zero cardiotoxicity, is great, but not if the increased dosing that this reduced toxicity affords impacts other parts of a patient’s health – and it looks like this might be the case with annamycin. There is no telling for sure, but that might be why the last developers dropped it.
Moleculin material would have us believe otherwise, however. Comparisons to the recently announced Jazz Pharmaceuticals plc – Ordinary Shares (NASDAQ:JAZZ) buyout of Celator Pharmaceuticals Inc (NASDAQ:CPXX) suggest a similarity, and promotional material seems to imply this similarity bodes well for Moleculin. Both companies are in the same space, but that’s where the similarity ends.
In the interest of balance, it’s important to mention that the FDA is often more lenient when it comes to the safety profile of drugs designed to treat serious conditions in unmet needs. If the choice a patient faces is some serious potential side effects or death, chances are they will choose the side effects. The agency considers this as part of its cost benefit analysis come review time. So, even with a relatively weak safety profile, the FDA may be willing to approve a drug like Annamycin because there’s no other real option for the patient’s it’s targeting. This is perhaps the biggest plus for annamycin’s safety profile.