Summary:
FGEN stock was crushed last week on strong votes against Roxadustat in both DD and NDD by FDA AdComm Big-Mover event
In battle of statistical experts/analysis, FDA's negative Roxa safety analysis beat FGEN's more favorable comments/spin in the view of AdComm members.
There is still a small chance that Roxa will be approved by the FDA for a limited population and an unfavorable label
Most likely, Roxa approval in U.S. will depend on another long, expensive study with newly proposed dosing regimen
FGEN has a number of important upcoming catalysts left in 2021
Did the market over-react to the negative AdComm votes? For our sister company, Amp's, viewpoint on this question and whether FGEN seems to be a good investment currently, read our full article HERE, after signing up (locks in our current introductory pricing). Learn more here.
Want to get Catalyst Events and stocks to watch sent directly to your inbox each week? sign up for our free weekly newsletter
INTRO
The FDA advisory committee (AdComm) meeting for Rox adustat (Roxa) for the treatment of anemia in dialysis dependent (DD) and non-dialysis dependent (NDD) patients with chronic kidney disease (CKD) occurred on July 15, 2021, as scheduled. This event was one of our BPIQ.com July 2021 Big-Mover events (Subscribers see Big Mover page here). Our assessment of the importance of the event to FGEN combined with stock options data, correctly indicated that a strong positive or negative was likely to move the stock more than 20%. Unfortunately for FGEN and its investors, and to our surprise, the AdComm panel members voted overwhelmingly against approving Roxadustat in both DD CKD (2 yes/12 no) and NDD CKD (1 yes/13 no).
BACKGROUND
For background on FGEN, Roxa, and this Adcomm, see our prior free blog post (Is FGEN a Buy Going Into Roxa AdComm? blog post) or subscribers can read our more in depth article (Is FGEN a Buy Going into Roxa AdComm? forum post), and see the 67 page FDA AdComm briefing document as well as the 154 page FGEN Adcomm briefing document.
The Negative FDA Viewpoint on Safety Won over FGEN's more Positive view of the data
In a battle of statistical experts/analysis, FDA's negative Roxa safety analysis beat FGEN's more favorable comments/spin in the view of the AdComm members in both the DD CKD and NDD CKD studies. This conclusion is based on both the highly negative votes against Roxa approval and based on the committee member comments to support their vote. The committee appeared concerned about the safety signals that were presented for death, thrombosis, infection, and seizures (see FDA AdComm briefing document at pg. 58), and not convinced by FGEN's explanation (See FGEN Adcomm briefing document at pg. 64) of the events in NDD CKD, mainly that they were caused by an imbalance in patient drop out rate for NDD CKD, and not convinced that the proposed dose lowering in DD CKD with the expected lower Hemoglobin rise would mitigate the issue without actual study data at the lower dose.
As we discussed in our prior free blog post (Is FGEN a Buy Going Into Roxa AdComm? blog post) and more in-depth subscriber post (Is FGEN a Buy Going into Roxa AdComm? forum post), the FGEN Roxa situation highlights a number of challenges for investors, especially retail investors. One huge challenge especially for retail investors is the amount and complexity of the data and analysis. This issue appears to have been confounded by the apparent lack of disclosure, or misleading disclosure by FGEN of some important findings, although we have not gone back to all the prior FGEN data to confirm this. See for example, the FDA's analysis of thrombosis in the Roxa trials (FIG. 1).
FIG. 1. FDA analysis of thrombotic events (see FDA AdComm briefing document at pg. 65)
This issue of missing or misleading disclosures will likely will be central to a future class action lawsuit, that seems almost inevitable given FGEN's concession that at least one of their previously data presentations was misleading (See our prior article here). Furthermore, we don't recall much disclosure re: increased thrombosis, infections, or seizures in the prior presentations of Roxa safety analysis before this past weeks AdComm briefings and presentations, although as indicated, we have not double-checked all the prior FGEN presentations and SEC filings. Furthermore, even at their briefing documents for, and presentation at the AdComm, FGEN stressed a 1.3 Hazard Ratio 95% confidence interval cutoff for MACE analysis (See FGEN Adcomm briefing document at pg. 45), but the FDA indicated in the Q&A session that they specifically would not agree to that cutoff in discussions with FGEN, and instead requested a cutoff of 1.25. Finally, FGEN repeatedly discussed their increased hemoglobin data for Roxa, above that of ESAs, as a positive result, even though they knew that the rate of increase and level of hemoglobin had previously been identified as a likely factor in an increased risk of MACE events for ESAs.
There is still a small chance that Roxa will be approved by the FDA for a limited population and an unfavorable label
The questions posed by the FDA for the AdComm and votes were as follows:
1) Should roxadustat be approved for treatment anemia due to CKD, in adult patients not on dialysis? (13 NO and 1 YES) and
2) Should roxadustat be approved for treatment anemia due to CKD, in adult patients on dialysis? (12 NO and 2 YES)
(See (see FDA AdComm briefing document at pg. 14).
Note that the questions did not for example, ask whether Roxa should be approved in certain subgroups of patients. Several AdComm members in their no votes particularly for the DD patients, mentioned that there vote would have been different if they were specifically asked the question regarding ESA hyporesponders. We did not hear any of the AdComm members reply regarding incident dialysis (newly initiated dialysis) patients. However, this might be an interesting subroup for Roxa too, since Roxa appeared to perform better in this important subgroup. Of course in our prior blog and forum posts and as played out recently in the controversial FDA approval of a different and related drug, Aduhelm (FDA Grants Accelerated Approval for Alzheimer’s Drug), the AdComm votes are not binding on the FDA. However, given the FDA's negative Briefing Document and presentation at the AdComm, a broad label approval for Roxa in DD and/or NDD CKD appears extremely unlikely. Nevertheless, there is still a small chance that Roxa will be approved by the FDA for a very limited population, with a black box warning for increased risk of thombosis, seizures, and infections, and with a post-approval study requirement. Most likely, Roxa's eventual approval in U.S. will not occur for some years, and will be dependent on solid efficacy and safety data in an additional long, large and expensive clinical trial(s) using FGEN's newly proposed dosing regimen targeting a lower hemoglobin level (See FGEN Adcomm briefing document at pg. 74). However, as mentioned, there is a slight chance that the FDA approves Roxa for a limited patient population and with warnings, especially for the limited ESA hyporesponder population.
It is interesting that FGEN has a number of important upcoming catalysts left in 2021. Is there significant upside in these, or is FGEN headed for further negative returns? Did the market over-react to the negative AdComm votes? For our sister company, Amp's, viewpoint on these questions and whether FGEN seems to be a good investment currently, read our full article HERE, after signing up (locks in our current introductory pricing). Learn more here.
If you are serious about investing in biotech stocks BPIQ is the research companion that will take you to the next level.
Save yourself time by accessing our database of over 550 companies, 1,800+ of their drug assets, and tools including: Catalyst Calendar, Big Movers, Company Pipelines, and more!
P.S. We are currently running a sale - lock in the price before it's gone
See what our members are saying about us:
Mike from United States
“Really loving the site over the competitor... like the layout and speed over the competition...like the individual pages for each drug/treatment”
Carl from United States
“I like your service. I haven’t seen anyone else doing something similar...nothing like this available for retail.”
Essey from Canada
“Love what you’re doing, this website is awesome.”
James from United States
Great site and I see it’s a family run business, great job.”
This article is not investment, tax, or legal advice. Please do you own diligence and seek advice from professional advisors representing your interests.
Article history:
7/18/21 initial published at ~ 7PM Central
Comments