Jim, did you learn the lesson of CYTR? I don't think so. It's a common mistake of hype-happy managements. Push a drug into advanced clinical trials so you can hype the company stock as a "clinical-stage" company. It is invariably a prescription for disaster. Yes, management does matter. And no I don't hate Leo. He may be a wonderful bean counter but he has no experience running a pharma company and is foolish enough not to seek advice and experience from others who can provide it.
Then there is Menon. Please look at his LinkedIn profile. Seriously? It looks like the rantings of an extreme egotist. Instead of listing what he did and does for a living, with things like titles and job responsibilities (like the rest of the world), Menton takes credit for everything (did he also invent the Internet with Al Gore?). He even takes credit for the idiotic notion that Prurisol should be a 505(b)(2) candidate, which this weekend's discussion showed (the part we all agreed on) will lead to generic substitution (but which a regular NDA filing may not, irrespective of anyone's speculation if the API works for psoriasis or not).
Yes management is important and, as activist shareholders, we have a duty a responsibility to fix such problems.
Sorry sic, but that article contains much opinion and speculation. What is needed here are facts. The sulfate salt gets the label if Leo is dumb enough to go 505(b)(2). Given that there is no adult supervision at CTIX, no one will dare challenge the king as lord of his fiefdom. That is a prescription for incredible dumb moves. The acid test comes if a partner is willing to step up to the plate and save Leo from himself. Again, we cannot predict clinical trials and speculation doesn't cut it with the FDA. The rules are THE RULES.
Rather than read (and believe, yikes) Leo's summary, I looked at the actual patents and their claims. It's a thin reed on which Prurisol rests. I still think anyone so motivated can look at a different anion (instead of sulfate) and show bioequivalence to Prurisol and get quacking on the market with a 505(b)(2. And that assumes that Leo wises up (big assumption) and drops the 505(b)(2) type of NDA in favor of a full clinical trial routine.
May not be able to respond as I'll be heading to H in terms of TSA lines and then the over-crowded skies. I'm sure many will not miss me.
Thanks rayon. I'll leave it to my colleagues to work on that one. If I knocked out a Ginsburg patent, it would be poetic justice in view of our being on opposite sides in another case. He tried to blind side me with prior art. It isn't personal (I like him), we were both doing our jobs.
Sorry rayon, but there are rules in 21 CFR. I didn't write them but I have to live with them. I understand that you don't scientifically agree with them, but welcome to my world, where whether or not I agree is not relevant.
you've stated: "So it is known that drugs like abacavir improve psoriasis in HIV (+) patients." Do you have a reference for that knowledge? The reason why I ask is that such a reference is likely prior art to the Prurisol patent. It also could mean that the patent could be invalidated with that art. If that is the case and there is a publication somewhere showing abacavir sulfate is useful for treating psoriasis as well as its hiv indications, this could invalidate the method of treatment claims as not novel and render obvious the compound and composition claims. The bioequivalence data supports invalidity.
I don't have time to knock out this patent but these are shark-infested waters and I'm not the only shark.
You can fell safer from generic substitution only if CTIX abandons is misguided notion of a 505(b)(2) NDA approval. A regular full monte NDA can keep the psroriasis label indication off of generic Z. But bioequivalence goes both ways and gives Prurisol also an HIV label indication.
You're off-course. You asserted, correctly, ("Only the holder of the NDA/BLA can do this: change the label.") But the problem is that the CTIX "Dermatology Overview" deck clearly states Prurisol is being pursued under a 505(b)(2) NDA. That is a two-edged sword. If CTIX supplies data showing the API works for psoriasis, all approved abacavir API products get the label copy. Bioequivalence goes both ways.
While we don't know if abacavir sulfate salt actually works for psoriasis like the abacavir ester possibly does, I would guess the probability is high the API works irrespective of a sulfate salt or an ester because the bioequivalence data in slide 22 is so compelling. But let's focus on the reality of the FDA regulations, not trying to speculate on clinical trial outcomes.
My main thesis in posting is my concern that Leo (and likely Menon too) are incompetent idiots and are ruining the value of the company drug assets. The problem is that there's no adult supervision of these two inexperienced incompetents. That often comes from an industry-experienced Board. But CTIX doesn't have that. All hail King Leo, the ruler of his fiefdom, and don't question his "wisdom." That's a prescription for disaster.
Clearly, a 505(b)(2) NDA for Prurisol will lead to massive generic substitution. Skipping this expedited approval process in favor of a full monte of clinical studies, according to your scenario sci, can reduce the risk of massive generic substitution (meaning: I agree with you but only without 505(b)(2) approval) but still leaves the product vulnerable for competitors seeking their own branded generic (different salt perhaps) and then doing an expedited 505(b)(2) themselves on Prurisol. The pharma world is Darwinian capitalism at its finest and children like Leo have no business playing in the Big Leagues. The July 8th slide deck proves this.
Your problem isn't with me, Jim. Your problem is with CTIX. The slides clearly show bioequivalence and the 505(b)(2) registration plan is a legally binding admission to equivalence. You can speculate all you want, but it is completely irrelevant to real-world generic substitution. READ THE JULY 8 "DERMATOLOGY OVERVIEW" PRESENTATION.
It's getting too hard to follow the discussion. Sci makes points about the need for clinical studies if Z (abacavir sulfate) can be generically substituted for P, the abacavir ester. I disagree because of legal/regulatory issues and not because of potential unpredictability of the science.
Please go back and look at the 2-day old slide deck entitled "Dermatology Overview" on the CTIX website. Slide 11 shows 505(b)(2) for P. Slide 16 shows "being developed under a 505(b)(2) development pathway for the treatment of psoriasis with the advantage of an established safety profile based on Ziagen (abacavir sulfate)." There is also a mechanism of action slide showing IL-20 and PRIVS as target. As an aside, I really like the fact that PRIVS is cited because of another project/company that also has an inhibitor for a long non-coding RNA.
The key slide is 22 showing bioequivalence (N = 16) in volunteers as "an equivalent systemic exposure."
We can speculate all we want about whether or not abacavir sulfate will work for psoriasis. But, from a regulatory standpoint they are bioequivalent because CTIX is using the 505(b)(2) pathway. I've long ago come to realize that trying to predict outcomes of clinical trials is way above my pay grade. But here the 505(b)(2) pathway is a legal admission the sulfate salt and the ester of abacavir are bioequivalent.
That means that HMO's like Kaiser (the Big Kahuna of HMOs) will have formulary and pharmacy meetings and REQUIRE that generic abacavir be used for psoriasis patients instead of more expensive branded Prurisol. My continuing of the Rayon scenario showed generic switching at the level of the PBM (pharmacy benefit manager) and not at the doc level. There would be no liability for the doc Dr. Yellen.
So while Sci raised valid and interesting points about predicting activity with different salt forms, such as amlodipine (I take generic amlodipine besylate 5 mg/day, along with fish oil, Costco big bottle), this debate is 30+ yrs old
Let me provide another situation where the branded manufacturer is trying to use cellular uptake when the pharmacokinetics match. Look at nab-paclitaxel (Abraxane) that is marketed by Celgene. A generic just filed an ANDA and there are one or two possible 505(b)(2) NDA's for micellular formulations of paclitaxel (often called a "brick" because it is so insoluble in an aqueous environment). Under Hatch Waxman, instead of filing a lawsuit to the sub-IV cert, Celgene filed a citizen's petition. I think it is online somewhere but I already have the pdf. Celgene knows that the Orange Book patents, with 8-10 years more term, are not enforceable so this became Celgene's defense against the generic ANDA. But the two micellular formulations (Abraxane is HSA-coated "nanoparticle") also fall apart in the serum and get transported in the serum as albumin-bound. So Celgene's citizen's petition indicates that standard bioequivalence clinicals (showing curves within the 80-125% ranges) are not sufficient to show bioequivalence. Given the rapid cleavage of an ester bond in the plasma from esterases, I doubt there is any bioequivalence differences or activity differences between the salt Z or the ester P. The phase 1 study curves are so closely aligned and support that theory. (Disclaimer: I worked on a paclitaxel micellular formulation project, and I own shares in my portfolio of one of the micellular product companies.)
I was able to grab that chapter that you referenced. Firstly, I don' think mechanism of action is much of a factor in drug approvals. The 505(b)(2) process for approval looks at substantial bioequivalence and focuses on pharmacokinetics.
But I cannot post on some of the projects I'm doing now, which may be relevant to the issues you raise. One involved an initial invention for a new use of an existing drug. The new use represented a larger market segment than the approved indication, where the drug did not work very well (in order to maintain anonymity I cannot name the drug or the new use because the patents issued). But we go nowhere when we went to the company marketing the branded drug. They wanted a full clinical trial but we only had open label (off-label really) use. Then we set up a company ad went to VCs to fund it. They all turned us down due to generic substitution since the drug was going generic soon. We only now (years later) got the company funded and starting a clinical trial. But it took something extraordinary, namely a new dosage form and a personalized segmentation of dose test to prevent generic substitution because a sub-population needed a lower dose than the generic.
The data in the slides shows a very high pharmacokinetic correlation between Z (generic) and P for the API. The curves match. CTIX has the data to file a 505(b)(2) NDA now. But that gives market entry for P with a generic indication and a black box warning. Given brutal margins, that is not the business of CTIX.
Let's continue with the scenario rayon is outlining (and thank you rayon for responding to the insane Jim posts, I don't have time). Dr. D the dermatologist (after large sums of money have been spend to get Prurisol approved and former college cheerleaders hired as sales reps to wine and dine docs) writes the scrip for Prurisol for his patient with psoriasis. Then P the patient, who is covered by health insurance, goes to get the scrip filled by sending it to her local pharmacist. The pharmacist looks up the health plan of patient P and finds that there a generic with the same API at the same dose and it's generic. The pharmacist informs the patient she can have branded Prurisol at a co-pay of $250 per month or get the same API drug that is generic at a co-pay of $10 per month. Which do you think the patient will choose? Welcome to generic substitution.
I'm human and can only do so much in a day. Not to make excuses for what Rosen did, but I have too many other fish to fry. And this is not the area where I work. But I also don't judge lawyers by their clients, even ax murders get representation. And that is the problem with this kind of a lawsuit, it is filed before there is a client. There was a federal law passed in the late 1990's trying to level the playing field for shareholder lawsuits. Perhaps this should be revisited.
To the API, no. Making a pro-drug (which is what Menon did) does not change the API. More straw man stuff Jim and do not confuse "the molecule" with the API.
Freddy, if you want to save the world, focus on the situation in Dallas and the underlying causes. That's a problem in need of a solution(s). The situation with Rosen shareholder lawsuits is minor and self-inflicted.
continued.. Either way, the situation with Prurisol proves that Leo is mismanaging company assets and violating his fiduciary duty to the shareholders. Like any addict drunk on his own hype, Leo first needs to admit his mistakes, drop Prurisol and focus on the remaining two potential drug assets to de-risk them. Or, for the sake of the share price, bring in an experienced, competent Board and leave.
As much as skeptics, like Jim, misrepresent what I post, I'm tired of repeating myself. If you're tired of my thesis, stop reading, it's all been posted before.
My thesis is that Leo is incompetent to run a pharma company. That is why the stock price is in the dumps. As shareholder, we need to think more like activists to improve this company, which is basically three potential drug assets, where only 2 of the 3 have potential. But value is inverse to risk in pharma and the key to augmenting value is to derisk assets. That takes money to run clinical trials well, with larger N numbers.
Turning to Purisol, I think it should be dropped as a worthless waste of precious capital. If I get psoriasis, my insurance carrier will try to treat it with generics. PBM's (pharmacy benefit managers) will look to generic substitution for any scrip written for a branded drug. That is reality in the US due to extremely higher branded drug prices than anywhere else in the world. That means that so long as the API (active pharmaceutical ingredient) of prodrug Prurisol is generic, it will be substituted. Is the prodrug composition novel and not obvious? Yes and the issued patent shows that. But the patent is a worthless waste of resources so long as a generic can be substituted to also deliver the API to patients.
The reality is that CTIX doesn't have any partners for any of its drug assets. Has anyone stopped to ask why this is so? Certainly not the Leo hype echo chamber (e.g., Jim, Leo, Frankie, etc.). Prurisol cannot be partnered. There is no market for an API that also has a generic. So why has Leo invested money in Prurisol? I don't know the answer to that one. Possible explanations are that Leo is so drunk on his own Kool Aide that he doesn't realize how dumb an investment that is. Or that Leo knows that the retail shareholder base is so gullible that they don't realize how worthless Prurisol is. Jim proves that theory. continued....
And as investors, we care about this? Why? It is a waste of time.