Eiger BioPharmaceuticals published a press release yesterday announcing that their ULTRA Phase 2 clinical trial investigating Ubenimex for lymphedema did not achieve their endpoints, and that they would not be pursuing additional clinical trials at this time.
The ULTRA trial was designed to evaluate the possibility that the drug known as Ubenimex (also called “bestatin”) could be useful for reducing the symptoms of primary and secondary leg lymphedema. Specifically, they were looking at changes in skin thickness and excess fluid volume in 46 lymphedema patients treated with either 150 mg of ubenimex three times a day for 24 weeks, or placebo pills.
Unfortunate, but not unexpected
The company concluded that their clinical trial:
“demonstrated no improvement of ubenimex over placebo in the primary endpoint of skin thickness and secondary endpoints of limb volume and bioimpedance”
It’s an unfortunate outcome. Ubenimex is a safe drug that has been approved and used in Japan as a chemotherapy adjuvant for over 35 years, and early mouse studies for lymphedema were certainly promising. But we’re not surprised by this result.
As we reported in-depth last year, the excitement surrounding Ubenimex was overblown in the first place. Published press releases and interviews at that time misrepresented the results of the primary animal study underlying the clinical trial, and in doing so set unrealistic expectations. Communicating research data in an exaggerated way to attract attention is understandable and perhaps even unavoidable. But designing a clinical trial with questionable connection to the underlying research is a little bit more baffling.
As we reported last year, the research underlying this clinical trial suggested that:
“Ubenimex (bestatin) may help NEW lymphatic injuries heal, but ONLY if natural healing is biologically possible, and ONLY if it is given at the right time and right dose. In contrast, the press release implicitly suggests that bestatin may reduce the symptoms of lymphedema regardless of the underlying plumbing problem and divorced from the normal healing process – which is not supported by the available data.”
Stated simply, available data tells us that we should only expect Ubenimex to have an effect if natural healing processes are active, and healing is possible.
Therefore, Ubenimex MIGHT be expected to:
- Help prevent the onset of secondary lymphedema by encouraging the natural healing process.
- Help prevent lymphedema progression in primary and secondary lymphedema by helping natural healing processes deal with ongoing inflammation and injury arising from unmanaged fluid accumulation.
But this is not what the clinical trial investigated.
I get it, establishing a role for Ubenimex in lymphedema prevention is MUCH more difficult (and therefore expensive) to investigate in a clinical trial. But the available data does not support the hypothesis that they decided to evaluate in their clinical trial, namely that Ubenimex could reverse symptoms in established (and presumably well-managed) cases of lymphedema.
No doubt Eiger BioPharmaceuticals had a rational business case for running the trial, and perhaps it was inexpensive enough to warrant a Hail Mary attempt, but they shouldn’t be surprised by the outcome.
There may still be something exciting here
I was thrilled that a pharmaceutical company decided to fund a clinical trial for lymphedema, and hopefully this will spur others to consider this untapped market. Kudos to Eiger BioPharmaceuticals. More importantly, the underlying animal research behind this trial is very well thought-out and exciting, and I’m certain the authors will continue down this road. The research is particularly exciting with respect to preventing symptom onset and/or progression.
Eiger BioPharmaceuticals also reported that their results might suggest that some individual patient responses could be interesting enough to warrant further exploration (but not by them), and that they would be open to further clinical trials if someone else came to the table to help support them. This may simply be the company trying to save face, but it wouldn’t surprise me if there were truth to these statements.