Kevin CC

Kevin CC
Contributor since: 2012
Interesting that the author and none of the people making comments bring up the 'obviously fabricated' data from the Ukrainian site for study 301. If you listened to the Adcom it was painfully clear the FDA knows this data is fraudulent (they do not suspect the company of any foul play though) and without it 301 was not stat sig.
Drug may get conditional approval anyway but this issue is a huge issue people seem to be ignoring.
Good article David. I moved out of SGMO much too early but shared your view the expectations at this point are far too high.
Keep in mind you don't want to look at vehicle-adjusted cure rates for this indication like you would with placebo-adjusted rates. The vehicle is still part of the treatment and it's the total cure rate podiatrists will be looking for.
Tava is definitely approvable but it is currently inferior to IDP-108 until more data says otherwise and will come to market after IDP-108.
Not really. It's possible but in the end I believe Tava is likely just inferior to IDP-108. The best thing Anacor can hope for is the FDA to uncover some blemish in the IDP-108 data but I'm a skeptic on that front too. If there is an ad-com for IDP-108 and the FDA provides a free live broadcast I'll listen in hoping to glean some new information. I'm not holding my breath though.
It may very well not reach the same efficacy levels. Keep tabs on IDP108 though. It will be interesting to see what Valeant prices it at. I'm curious what your source for the 'rumor' is.
Many joke about the long list of side effects of drugs on TV commercials but some need to be reminded not everyone experiences side effects and when they do it doesn't mean they experience them all. Sounds like common sense but I'm often surprised at the number of people who don't seem to realize this.
Thanks for reading.
Lawsuit isn't big news:
Thanks deut, I also didn't go into any detail on GSK 052 being handed back to Anacor in October or their work in psoriasis (shelved till further funding comes in). The story is a nice one.
I almost wish an advisory committee for Valeant's IDP 108 would be announced. I'd like to read the FDA's briefing documents for additional insight.
Thanks for reading.
If by 'conditions are horrible' you're referring to the side effects of these drugs then yes, they can be. But keep in mind not all patients experience them and the relief they provide is often worth the risk. RA drugs wouldn't be billion dollar sellers if patients didn't think so.
On bone disease progression: the drugs actually can stop progression...but not forever. Usually an RA patient will progress through a series of DMARDs because of adverse events or the drug stops working for them. I can't find the exact number in my notes but I seem to recall a patient is on an RA drug for an average of 5 to 7 years.
The link below is to a previous article citing the FDA briefing docs (bds) about disease progression. Under 'The Surprise: Efficacy' check out #2. Link to the BDs is in first paragraph of the same section.
Thanks again for reading.
It very well may get approval but I'm wondering how big an issue the lack of radiographic data will be to the FDA. Read my most current article on tofacitinib for more details.
I have to disagree about where tofa gets used. I suspect it will be prescribed largely after the anti-TNF blockers. Time will tell thought.
Thanks for reading.
The report you refer to is actually the briefing docs and are not a product of a committee but rather an FDA staffer. If memory serves her name was Dr. Melanie Blank. Typically 'panel' and 'committee' are interchangeable terms referring to the group of experts gathered to provide their expert opinions by the FDA.
I'm not advocating stringing along investors so management can continue to get paid but it happens all the time. I'm actually struggling to recall a biotech that closed doors because all their compounds were lousy...which is different from closing doors because they went bankrupt.
Also, I don't believe RNAi is a bogus space but it certainly wasn't (and still isn't) ready for primetime.
Tmeyer: I have neither LT or ST pps in mind for HZNP. If I do buy back in it will be on a meaningful pullback. I previously bought in on a dip around 5.80 and sold in the 7s. I have absolutely no intention of holding through PDUFA. Looks like a big 'sell the news' whether approved or not. I'm beginning to focus on run-ups and staying more away from holding through defined catalysts (PDUFAs & data readouts).
Jtricks: I do believe CHTP managements' intentions are good but they have definitely made some mistakes along the way. I don't think it necessarily makes them incompetent but it does underline their inexperience. If they fail to learn from their errors I'll happily pin the 'incompetent' label on them.
I can't think of any examples where investors know the numbers of patients enrolled at individual sites. Also don't know if sites ever get told there is a limit to their enrolment numbers. Interesting question.
301 was so statistically significant it didn't require a confirmatory trial true but the FDA making that call and deciding not to approve because of the one site are two separate decisions that are made at two different times and likely with two different sets of data (or more specific data). It's also possible the FDA changed their mind and decided they needed to be concerned about that one site.
CHTP was aware of the one site and that is why they conducted two independent audits of the site. The FDA also conducted their own audit. No problems were found by anyone.
I plan on sitting down and reviewing the ad-com transcript because I think FDA staffers (Temple, etc) present (beyond the one who wrote the BD) stated the length of trial was sufficient. It could be both issues resulted in the CRL. Notice the CRL suggests a trial to confirm the efficacy of 301 (the site issue) and recommend duration of 2 to 3 months (durability). I suspect the FDA would have approved Northera even with the durability question unresolved if the site issue did not exist. I think the FDA suggesting a 2 to 3 month trial in the CRL and then agreeing to something less than 8 weeks during End of Review meetings supports my belief.
Unless the RA data is a home run (a clear benefit regarding tolerability and safety AND ACR20 in the mid to upper 60s) then I don't plan on holding till a partnership. I will sell after data release and wait till after expected dilution before considering a re-entry. That's the plan for now anyway.
I also wanted to add that the FDA's issue with the one site in 301 is precisely because there is only one trial required by them. I didn't include it in the article but the bit about one site shall not be disproportionately responsible for the favorable effects seen applies in instances where there is only 1 study. That's what we have here.
The concern about the one site for study 301 is not new but I honestly can't recall when it first showed up. I can tell you when it first appeared/was mentioned it was not a topic of focus. It seems to have more focus now and that is new.
You're getting 301 and 302 confused. 302 data came first and 301 had the changed endpoints. Changing endpoints during the study does sound crazy but the FDA agreed every step of the way (SPA still intact). Further, the briefing docs, the panel, and the CRL had no issue with the changed endpoints.
Also, because 301 was so highly statistically significant, the FDA informed CHTP that a second trial confirming efficacy was not required (this decision by the FDA came AFTER they had already told the company another confirmatory trial, 306, would be required). So to summarize, efficacy from 306 was originally required for approval but then the FDA changed its mind and said it wasn't required. This is why the FDA has allowed them to file with just the lone success trial in 301.
As far as 4051 is concerned it does not need to show better efficacy than MTX to be a real drug that will be used by rheumatologists in treating RA. Still, it would be nice to see superior efficacy and I think there's a real chance it can occur. The very low dose of 0.3mg had an ACR20 score of 37%, the 1mg dose an ACR20 of 53% so we're trending in the right direction as dosing increases.
In a comparison of equal doses of 1504 and 4051 the former may prove more efficacious but it really doesn't matter. The theory is 4051 is much more tolerable and this has been born out in preclinical studies and p1 studies. CHTP can use higher doses of 4051 then it could with 1504 and that's why you can expect to see greater efficacy. Forget about 1504.
Thanks to everyone for reading and providing comments.
BioBobby, I'm going to listen to the call for a 3rd time and make some notes. There's certainly much more risk and open questions regarding Northera and I'd likely be completely out of $CHTP if it weren't for 4051.
Hope to write something up very shortly.
Big pharma too large and complicated to get a handle on as far as I'm concerned. You'll have to decide that for yourself.
Still waiting to hear more from panel members but I'm skeptical about approval and think there's lots of opportunity for other oral drugs to take market share away from tofacitinib if it does get approved.
I need to make a correction to my article above. I incorrectly refer to tofacitinib as being a biologic like Humira, Remicade, and Enbrel. In fact it is not a biologic but rather a small molecule. This escaped my proof-reading.
Thanks to DrMBA for catching it and bringing it to my attention.
Really enjoyed your article Dan. I didn't think anyone other than Dirk spent the time to write about the RNAI space.
I remember increasing my position with TKM thinking that getting listed on the NASDAQ could only help the stock price in the short term. In theory it was a good plan but waiting in the bushes was that dreaded Roche announcement. I ended up selling for a loss instead of the tidy profit I had staring me in the face. Still, like you, I had and still have a soft spot for TKMR.
I've kept up on the space and been hoping to get back in. By the way, I also owned ALNY but sold that when it became grossly overvalued in the high 20s.
Again, good job.
I agree with your timelines for Northera if a brand new trial is started.
Also agree there's no way CHTP goes into p3 with 4051 w/o a partner. Management has stated they intend to partner before p3. That said, I'm not looking so far out that I'm worrying about competition with MTX. If 4051 shows comparable efficacy and a superior AE profile in p2 the stock will appreciate. After that, there is the potential for partnership.
From here, I'm long into June - July and will reassess with more info (results of FDA talks, 4051 results) in hand.
Unless there are design changes (additional patients enrolled for powering, different primary endpoints) AND the FDA is supportive of these changes (I'm not looking for an SPA here) then I'm skeptical about data from 306b being enough to convince the agency to approve.
I'm still long the company for a few reasons:
1. I think Northera is a real drug that works. Eventually, I believe it gets approved. Sooner than later is always nice.
2. The possibility of a falls label claim combined with the drug's favourable side-effect profile is enticing. I know this point also assumes eventual approval but signs are encouraging so far.
3. I believe we see good data in June 2012 from their p2 RA drug CH-4051.
4. I don't buy simply because something looks cheap. But I do if it's cheap and I like its chances for success. For me, that's what I see with Chelsea.
Management misleading investors is always a possibility but I don't believe that's the case here. Before the company received the briefing documents (BDs) there was little reason to doubt approval. The doubters mainly cited the switching of endpoints in trials. My opinion all along was this was a non-issue. Management also didn't feel it was an issue. Interesting to note the BDs didn't focus on changed endpoints as a major problem. Bears were right on the outcome but for the wrong reason.
When I read the BDs the questioning of the durability of effect was the only issue I was nervous about. Obviously once they received the BDs management likely felt their chances of approval dropped but I don't believe they misled us about the chances of approval leading up to then.
That interim look at 306 bombed on the OHQ to be sure but at that point Chelsea basically split the study. The interim data reported became what is referred to as 306a. Consider that trial completed. Since 306 was no longer required for filing the NDA (the FDA confirmed this to Chelsea) the company decided to continue enrolling patients, changed the primary endpoint from the Composite OHQ to the falls endpoint, and is referring to the study as 306b. All along Chelsea has positioned 306b as a study supportive of a falls label claim. They are well aware of the FDA's guidance that obtaining a falls label claim requires another study, besides 306b, be run.
If 306b falls data is successful I still don't see this study, in its current design, being enough to convince the FDA. They've already stated they want another study proving a falls benefit.
Chelsea has been pretty good about not cutting corners in the past so I don't expect them to follow a path forward that the FDA is skeptical about. That said, if they do plan to make changes to 306b in the hopes of using it to fulfill the FDA requests be sure to ask them if the FDA is supportive of their actions. There is no SPA to confirm still exists for 306b like there was when primary endpoints were changed for 301.
Until PSTI gets to p2 and runs similar trials to what ASTM already has there's not much to compare.
Additionally, ASTM's p3 trials will likely require patients to have tissue loss at baseline as an entry criteria. This should help distinguish between drug and control arms as existing tissue loss is a good indicator that future problems, and possible amputations will occur. This entry criteria was NOT in place for the p2 trials and only a portion actually had tissue loss at baseline.
I have little doubt ASTM's therapy works but am realistic about the company's ability/chance of demonstrating stat sig results.
Long ASTM.
Your explanation of $0 sales in Q4 makes sense. But why would there be $5 million in sales in Q3? Are coupons not available that early after launch?
Lastly, is # of scripts accessible information?
I enjoy the intelligent discussion in the comments section. A nice change from elsewhere.
Jason, care to comment on the company steering away from the traditional sales rep model and into electronic advertising? Do you believe the company's assertion that 80%+ of docs rely on the internet instead of reps for info?
You had to ask for the data right? Did management say why they didn't include it with the press release?
Considering the importance of the future P3 design would you expect/encourage the company to seek an SPA?