In this article, I will focus on Eiger BioPharmaceuticals (NASDAQ:EIGR) and its development of treatment for HBV/HDV co-infections. I will discuss the science behind Eiger's two lead compounds and which one I believe is the better bet. While there are other companies working on treatments for HBV/HDV co-infections, Eiger is well ahead in clinical trials. Lastly, I will discuss lonafarnib as a treatment for HDV and the future of Eiger BioPharmaceuticals.
Hepatitis B (HBV)/delta (HDV) viral co-infections are the most aggressive form of viral hepatitisGlobally, it is estimated that 257 million people are chronically infected with hepatitis B virus (HBV) of which approximately 20 million are co-infected with hepatitis delta virus (HDV). HBV/HDV chronically infected patients develop rapid and severe hepatitis due to their infection. These patients have a 600-fold higher likelihood of developing hepatocellular carcinoma, aka liver cancer, than HBV mono-infected patients which already have an elevated risk as compared to the healthy general population.
HDV is a small RNA virus that requires an HBV co-infection in order to spread in the patient's liver and to form infectious virions. As such, people that have received the HBV vaccine are also protected against infection with HDV. HDV encodes only a single gene, the HDAg, that has two forms performing two different functions. While it is very small and is considered "simple", this is actually not the case in terms of treatment. As the virus highjacks the host machinery (DNA polymerase, RNA polymerase, …etc) to replicate its genome, it is difficult to develop inhibitors of HDV that do not also make patients incredible sick. One key part of the HDV life-cycle is that the HDAg must be prenylated, the addition of a hydrophobic lipid to the protein, in order for HDV to form a virus particle. As such, this is a good potential target to inhibit HDV.
HBV/HDV co-infections are considered by the FDA as a rare disease. As such, the approval process for HDV treatments is accelerated. In addition, there are currently no approved treatments for HBV/HDV co-infections. Eiger currently is the only company that has two treatments in development for the treatment of HDV. It should also be noted it is unclear the number of HBV/HDV co-infected patients in the United States (less than 200,000 reported as it is considered a "rare disease") but the Centers for Disease control (CDC) estimates that HDV diagnosis might be underreported by 20%.
Eiger's HDV treatments in developmentEiger has two different compounds in development. The first is pegylated interferon lambda (IFN-lambda), an innate immune stimulator. It is a human protein that activates the type III interferon receptor pathway which activates the JAK-Stat pathway leading to viral suppression. Pegylated interferon alpha (IFN-alpha) was the standard of care for HBV for almost 2 decades. IFN-alpha activates type I interferon receptors but still acts through the JAK-Stat pathway. IFN-alpha is now used only rarely in the treatment of HBV as it results in very terrible side effects and, as such, patients tend not to adhere to their treatment regimen. Type I IFN receptors are on several cell types, type III is on fewer cell types, and as such, Eiger argues that this will reduce the off-target side effects increasing efficacy and also patient compliance. In phase I/II fast track, trial showed that overall there was good tolerance. Eiger BioPharmaceuticals is moving into phase III trials. Keep close attention to updates about these phase III trials as they get underway.
Lonafarnib (LNF) is a prenylation inhibitor which inhibits the lipid prenylation of the HDAg. As such, the HDV virion is not able to exit from the infected hepatocyte preventing spread of the virus and could most likely reduce HDV viral load over time. This has been borne out by the clinical data showing that HDV RNA is the serum of patients reduces over the course of several weeks. However, the effect is not long lasting as when treatment is stopped, the virus is able to rebound. As such, Eiger is also performing phase II clinical trials where they combine LNF with pegylated IFN-lambda. This combination therapy, in theory, should prevent HDV spread and should reduce and possibly clear the HDV viral RNA from infected hepatocytes as the pegylated IFN-lambda would activate interferon stimulated genes resulting in targeting of the HDV genomic RNA for degradation.
The major issue with LNF is that it causes gastrointestinal (GI) issues in patients. This is usually manifested as diarrhea and discomfort. It remains to be seen if these side effects are going to become more severe with longer treatment regiments of LNF. Another option is that, with combination therapy with pegylated IFN-lambda, the amount of LNF used could be reduced and as such, the GI side effects will consummately also be lowered.
Eiger is also developing LNF for a different indication, the treatment of progeria. Progeria is a devastating rare disease where patients age at an accelerated rate. Patients with progeria have a significantly lowered life expectancy as well as quality of life. There is also no treatment currently available for progeria. It has been shown in phase II trials that LNF and prenylation inhibition can improve the quality of life and symptoms of patients with progeria. As such, it may extend the lives of these patients.
Can Eiger make it past the finish line?Eiger has $33.2 million in the form of cash, cash equivalents, and short-term debt. Its two lead compounds are heading into phase III trials (LNF and pegylated interferon lambda). Eiger's cash burn rate for the first quarter of 2018 was $8.8 million. As such, Eiger has enough cash to complete its phase III trial for LNF. However, to complete the two additional phase III trials, Eiger is about to undergo with pegylated interferon lambda mono-treatment and the co- LNF and pegylated interferon lambda study the company will most likely have to dilute shareholders by offering more of the company for sale in order to finance these adventures.
Advocacy by special interest groups for LNF treatmentEiger BioPharmaceuticals' two lead compounds are pegylated IFN-lambda in phase III and LNF both for the treatment of HBV/HDV infection. In addition, LNF is being developed for the treatment of progeria, a terrible genetic disorder. Eiger BioPharmaceuticals has a very strong collaborative relationship with two advocacy groups that will help with its approval of both of these treatments. The first is the HBV Foundation, the other is The Progeria Foundation. These are both powerful lobbying advocacy groups that will help Eiger get approval for these two compounds as they would be the first treatment for HDV and progeria.
ConclusionI think that it is imminent that Eiger will get approval of its pegylated IFN-lambda treatment for HDV as the phase I/II data showed efficacy in being able to suppress HDV in the serum of infected patients. As such, I believe that the phase III trials will be successful and will end later this year 2018 or early next 2019. This may soon be followed by approval of LNF in 2019-2020. In addition, Eiger is also working on approval of a combination therapy using its two compounds pegylated IFN-lambda and LNF. The phase II preliminary data looks promising for this combination therapy and should be completed 2018-2019. This creates a significant advantage as Eiger has three different therapies in development for HDV. There are other companies, MYR Pharma is one that is also developing its own therapies for treating HBV/HDV infection. However, Eiger is so far ahead in its development of LNF and pegylated interferon lambda that it will most likely be first to market. As such, all other potential drugs will be compared to Eiger's for efficacy. I predict that Eiger will be a leader in HDV treatment and is a great investment as a result. In addition, LNF might be approved for progeria indication creating another revenue stream for the company.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
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