Despite the recent EU approval of the first hepatitis D treatment, low public awareness remains an obstacle to tackling this aggressive infection.
Earlier this month, the peptide drug Hepcludex became the first drug greenlit for hepatitis D treatment in Europe. This was a conditional market authorization granted to the German company MYR Pharmaceuticals based on two phase II studies; MYR Pharma is now running a further phase II trial and large-scale phase III trial to obtain full approval.
The drug’s entry into the market seems well-timed by the European Medicines Agency (EMA), closely following World Hepatitis Day at the end of July.
Hepatitis D is a contagious and aggressive form of viral hepatitis, characterized by liver inflammation and damage. It’s caused by the hepatitis delta virus, which is transmitted in bodily fluids such as blood, semen, and urine. The hepatitis delta virus can’t work alone – it piggy-backs on existing hepatitis B infections and causes scarring and liver cancer much more quickly than any other form of hepatitis.
The hepatitis B vaccine prevents hepatitis D. However, for those who get infected by hepatitis D, one of the few treatment options is the off-label drug interferon, which arms the immune system against viruses. Unfortunately, interferon normally just suppresses the hepatitis delta virus temporarily, and the drug can have unpleasant side effects, such as nausea and headache.
“There’s some indication that after removal of interferon, patients still stay negative for the hepatitis delta virus, but the long term shows us the virus comes back,” said Stephan Urban, Professor of Virology at Heidelberg University, who led early efforts to develop Hepcludex. “So, interferon cannot cure the patients, or only very occasionally.”
To clear hepatitis D infections, Hepcludex prevents the virus from entering liver cells by blocking a protein on the surface of the cells called NTCP.
The media coverage of Hepcludex’s approval has been modest, which seems to reflect an ongoing lack of public awareness of hepatitis D. One reason for the inattention to the hepatitis delta virus is that most people are vaccinated against hepatitis B, and by extension, hepatitis D. Furthermore, the condition reportedly affects only around 5% of patients with hepatitis B, or around 12 million people worldwide.
However, vaccines for hepatitis B aren’t reaching everyone around the world, particularly in less-developed countries. And a lack of hepatitis D testing means the low official rate of hepatitis delta virus infections could be just the tip of the iceberg.
“For example, in the US, they say ‘we don’t see hepatitis D patients,’” Urban said. “If you look carefully, you see that less than 5% of those that have been tested for hepatitis B are tested for hepatitis D. They just don’t know.”
Hepatitis D diagnostic tools are available, such as a polymerase chain reaction (PCR) test, where viral genetic material in a patient sample is amplified and detected. However, hepatitis delta virus PCR tests are unaffordable for many deprived regions.
To address this, Urban’s group is developing a cheap, rapid hepatitis D test that could be used in the field. This could assist efforts to detect people with hepatitis D in some of the worst-affected countries such as Mongolia.
The hepatitis D diagnostics shortage seems to be a mirror of the worldwide problem with Covid-19 testing. As the pandemic swept the world this year, many European and US healthcare systems were unable to meet the demand for accurate and rapid Covid-19 testing.
“I think this whole discussion on [Covid-19] diagnostics – differences in the numbers, the death rate, etc. – really made it clear how important diagnostics are in order to know the viral threat,” said Urban.
Hepatitis D also provides a crucial lesson for biotech efforts to develop a Covid-19 vaccine: any effective vaccine will need to reach poorer regions. A vaccine for hepatitis B has existed for decades, yet its lower coverage in developing countries allows both hepatitis B and D to continue. Could this also happen with Covid-19 as rich countries clamor to bid for advanced vaccines and leave out poor countries?
Hepcludex’s approval is a big step forward for hepatitis D treatment. But it will need effective, multi-pronged diagnostic and treatment programs to distribute it properly, just like with effective treatments for Covid-19.
“It will raise the big questions; the big problems that will come like every drug,” Urban remarked. “Will you get such a drug available in poorer countries? How far and how fast will it go? And how good will their social and healthcare programs be?”
Image from Elena Resko