Besremi versus Pegasys

[EPguy]

This question was raised by Flynn2107 months ago. I looked into it and replied there but it seems worth a new post with the recent FDA approval.

PEG and Ropeg (Besremi) use polyethylene glycol (PEG) to control the release of the INF molecule. The earliest INFs had less of a control element and more places the PEG could attach to, or no PEG at all, thus needing at least daily shots and large variations in INF levels. This is known with insulin where keeping the levels controlled with slow release is best. Maybe a similar idea is working here.

The maker of Besremi states that fewer sites are better for control and the PEG site in Besremi is well limited to a single site:

<<The proline linker facilitates the synthesis of a single positional isomer which further increases its stability and half-life.>>

cancer.gov/publications/dic...

Pegasys has multiple possible pegylation sites. The maker of Besremi states that the single site is a reason Besremi acts longer, more evenly over time, with a more mild profile vs earlier PEGs.

In this study comparing PEGASYS and PEG-Intron:

pubmed.ncbi.nlm.nih.gov/129...

<<However, the different PEG moieties attached to the native protein, the site of attachment and the type of bond involved lead to vast differences with respect to the pharmacokinetics (including absorption, biodistribution, metabolism and elimination) and pharmacodynamics of these two compounds.>>

I've read that Pegasys is preferred between these two older drugs. This did not compare Ropeg, but Besremi's maker is very focused on this exact subject.

Further for Pegasys there are several different sites to which PEG can attach, I assume this is the "moieties" noted above:

sciencedirect.com/topics/me...

<<There are four main potential IFN-α2a pegylation sites, (for Pegasys) at lysine positions 31, 121, 131, and 134.>>

Few of us are expert enough to really understand it but I accept that these differences are important, where controlling the PEG site matters and Besremi has its main advantage by limiting this site to a single predictable and most effective location on the INF.

[Loooonglife]

My sense is that there are insufficient data that clearly demonstrate if either drug (Pegasys or Besremi) is superior over the other. What we need is a direct comparison of the two agents in a well controlled clinical trial. I hope this will happen soon, although neither the manufacturers of Pegasys nor Besremi might be overly interested in doing so. From a patient perspective it would be important to know if either drug has better tolerability while still achieving a robust hematological and molecular response in a timely manner.

[EPguy in reply to Loooonglife]

That would be nice to see. They do both seem to get good responses in their separate results, and PEG works well for many here. One note is how much variation there seems to be in PEG dosing among the members here. Maybe Besremi will allow for more consistent dosing as the mfg claims.

I wonder what, if any, data there is for Besremi's confident tolerability claims.

But while Besremi has no incentive for such a trial, Pegasys will likely need to do one against Besremi to get FDA if they want to stay in the US MPN market long term.

[EPguy in reply to Loooonglife]

There is a very small study on it.

ashpublications.org/blood/a...

<<Patient 002 experienced elevated AST/ALT while on PEG, which normalized after four q2 week doses of ROPEG (8 weeks of therapy). Patients 003 and 004 who had persistent fatigue on PEG, saw significant improvement of their symptoms after switching to ROPEG.>>

<<Notable observations include normalization of hepatic transaminases previously induced by PEG, maintenance or even suppression of one highly deleterious cytogenetic abnormality, maintenance of ET & PV remission, and amelioration of interferon side-effects with lower equivalent doses>>

The liver stuff here is in the warnings for Besremi, but patient 002 got better with the switch to Ropeg. I think some of the warnings for Ropeg are from historical experience with the broad category of INFs.

There is also one member, John SC, here who improved tolerance by switching.

healthunlocked.com/mpnvoice...

So we have a *very* small sample but it is a good result.