2023-03-29 14:15:25 ET
Summary
- FibroGen, Inc. got roxa approved in the EU and China, but not in the U.S.
- The data manipulation problem from two years ago still haunts FibroGen, Inc.
- That is why, despite some progress with its pipeline, I find it difficult to completely trust FibroGen, Inc.
I covered FibroGen, Inc.'s (FGEN) roxadustat data manipulation fiasco in May 2021, and have not covered it since. The company was on the verge of an advisory committee meeting in a few months. Right before the meeting, FibroGen management admitted that someone within the company manipulated trial data for roxadustat to make it appear more positive than it actually was. As I noted at the time, this means
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Some FibroGen employee/associate/investigator[s] at the clinical trial level thought that the HR data from the 1526-patient incident dialysis cohort and elsewhere wasn't good enough
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So they decided to change the "stratification factors" (partitioning trial subjects by something other than treatments given) nearly 2 years ago to make the data look better
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The 13-member, highly-qualified management team at FibroGen - who earn millions of dollars every year - failed to do their jobs of detecting such hocus pocus before it became public
This happened just before the company was planning to present data at the adcomm, and the company management said they were unable to determine if roxadustat reduces the risk of MACE+ in dialysis, and MACE and MACE+ in incident dialysis compared to epoetin-alfa. However this happened, roxa's safety data was called into question, although there was no issue with its efficacy.
This is old history, but let me quickly recap it because not many articles cover this ticker any longer on Seeking Alpha. Two months after this fiasco, the advisory committee roundly rejected roxadustat, and the FDA followed with its own CRL. Interestingly, Europe stayed independent of what was happening in the U.S., and approved roxadustat for the treatment of adult patients with symptomatic anemia associated with chronic kidney disease ((CKD)). This triggered a milestone payment of $120mn by partner Astellas to FibroGen, and the company will also receive royalties on European sales.
It is interesting to ask, but difficult to get a proper answer to the question why the EC approved FibroGen while the FDA did not. This happens quite often, but in other cases there could be differences of opinion on scientific issues. Here the issue seems not to be a scientific issue, exactly, but the manipulation of data which made the rest of the data suspicious. Apparently, the EC managed to overlook the ethical difficulties. My interest is: did the FDA also ignore the ethical component of the issue and focus solely on the scientific stuff? It is important to understand this because each response will have a different sort of outcome for FibroGen in the long run while it runs through another phase 3 trial.
Well, what the FDA said in their briefing report, as quoted on Seeking Alpha , is this:
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"You will discover that roxadustat's efficacy is comparable to that of ESAs; however, there are important risks of serious thromboembolic events, as well as other risks, with Roxadustat," the staff mentioned in the report .
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"The principal issue before the Committee is the drug's safety, and safety with respect to the specific CKD patient populations," they added.
So the EC focused on the efficacy, which was strong, and the FDA focused on the safety, which was troubling. I think, in this particular instance, the FDA did the right thing.
In retrospect, this looks like the correct decision because GSK Plc ( GSK ) reported positive phase 3 data for its own hypoxia-inducible factor prolyl hydroxylase inhibitor, daprodustat, for patients with anaemia due to chronic kidney disease ((CKD)). Daprodustat was eventually approved last month on superior results, which goes to show that the FDA may have taken a tough but correct decision. Admittedly, dapro has its own set of problems, especially in NDD-CKD patients, however, it was approved in the dialysis patient population for the time being.
There is also Akebia Therapeutics, Inc. (AKBA), whose vadadustat also got a CRL from the FDA for almost the same reason, safety issues surrounding data for MACE. Two of its phase 3 trials came out with differing MACE data, causing the rejection. As of last month, EC decision was pending.
Thus, the FDA will be looking for very definitive signals from the ongoing roxadustat trial regarding MACE. If FGEN wants U.S. approval, they better deliver it because now the market has GSK's medicine. With AstraZeneca ( AZN ) increasingly showing aloofness to roxadustat in CKD - see here - the path forward is looking tough for roxa.
FibroGen has another program, Pamrevlumab, which is an anti-fibrotic molecule running through phase 3 trials in 3 indications, Idiopathic Pulmonary Fibrosis, Duchenne Muscular Dystrophy and Locally Advanced Pancreatic Cancer. These are vastly different diseases, tied in through fibrosis, however the company clarified that there will be no read-through on efficacy.
In IPF, there are only two FDA approved therapies, and these neither stop disease progression nor are well-tolerated, producing an unmet need. Pamrevlumab produced strong phase 2b data earlier, and was generally tolerable. They will be announcing phase 3 data soon, and this could help improve the price performance.
Per the earnings call :
Moving chronologically, we expect top line data from LELANTOS-1, our Phase 3 trial of pamrevlumab in non-ambulatory patients with DMD in the second quarter of 2023.
Top line data from ZEPHYRUS-1, our Phase 3 trial in IPF in mid-2023. Data from our LELANTOS-2 trial in ambulatory patients with DMD in the third quarter of 2023. Now, looking out to next year.
Our LAPIS Phase 3 study in locally advanced pancreatic cancer is expected to readout in the first half of 2024, and finally our ZEPHYRUS-2 Phase 3 trial in patients with IPF is expected to report out mid-2024.
Roxadustat last year completed enrollment in a phase 3 study for treatment of anemia in patients with lower risk transfusion-dependent myelodysplastic syndromes. Data is expected in 1H 2023. The primary endpoint of the study is transfusion independence for ? 56 consecutive days in the first 28 weeks of treatment.
Financials
FibroGen, Inc. has a market cap of $1.77bn and a cash reserve of $443mn. Last year, the company had total revenue of $140.7 Million in 2022, from partnerships and through sale of roxa, largely in China, where it was approved in 2018. "Full year 2022 FibroGen's net product revenue under U.S. GAAP from the sale of roxadustat in China was $82.9 million compared to $47.6 million in the full year 2021, an increase of 74%." R&D expenses for the fourth quarter of 2022 were $61.6 million while SG&A expenses were $34 million. That gives them a cash runway of at least 4 quarters, ignoring income.
Bottom Line
FibroGen, Inc. is a complicated company and the company's miscommunications and reticence does not help matters. This is also a quite cursory review, and does not go into such details as a recent change in Pamrevlumab's endpoint and so on. From this quick look, however, I am not sure I like FibroGen, Inc. as an investment. My main problem is that this company took a once-promising drug and managed to ruin its approval in the U.S. This is not a company I can easily trust. FibroGen, Inc. will need to prove a lot more for me to be able to trust them.
For further details see:
FibroGen: Despite Some Progress, Roxadustat's Data Disaster Still Haunts It