Repurposing older drugs never approved in the US into new indications can be a lower-risk, if controversial, way for ambitious biotechs to become commercial-stage companies. But as Eiger Biopharma discovered, it is no guarantee of success.
The California-based company saw its valuation chopped in half yesterday following the news that ubenimex failed to improve symptoms of pulmonary arterial hypertension (PAH) in a phase II trial. Eiger was quick to focus on progress for ubenimex in other inflammatory indications as well as a separate hepatitis D project, but investors were unimpressed.
Leukaemia to hypertension
Ubenimex has been marketed in Japan for 30 years as Bestatin, a treatment used with chemotherapy to extend remission for certain types of leukaemia. Eiger licensed it two years ago, quickly gained orphan drug status in PAH and began phase II trials in mid-2016.
The agent blocks the inflammatory mediator leukotriene B4 (LTB4), inhibition of which in leukaemia has the effect of augmenting the response of the host immune system. In PAH LTB4 has been linked with inflammation leading to arteriole occlusion, vasoconstriction and hypertension.
Eiger’s hypothesis that blockade of LTB4 would lead to improvements in PAH symptoms was not borne out, however, with patients taking ubenimex in the phase II Liberty study showing no benefit in pulmonary vascular resistance or the six-minute walk test.
Data on ubenimex in lymphedema is due later this year, but it seems likely that investors are no longer assigning value to this asset. Even if had succeeded PAH would have been a tough market, with Eiger’s candidate going up against the might of Johnson & Johnson’s suite of Opsumit and Uptravi – a commercial partner would probably have been necessary (see table).
|Top five sellers in pulmonary arterial hypertension, 2022|
|WW sales ($m)|
|Opsumit||Johnson & Johnson||1,260||1,554||1,752|
|Uptravi||Johnson & Johnson||737||1,225||1,676|
Another Eiger phase II project, GLP-1 inhibitor exendin (9-39), is also due to report phase II data in post-bariatric hypoglycaemia, and its hepatitis D projects lonafarnib and pegylated interferon lambda are to be discussed in an end of phase II meeting with the FDA next month.
With the exception of exendin, which was licensed from academic institutions, the assets in Eiger’s advanced pipeline have origins in other pharma companies: ubenimex from Nippon Kayaku, lonafarnib from Merck & Co and the interferon from Bristol-Myers Squibb.
As a sign that Eiger has high expectations that this strategy will pay off, it recently appointed Eldon Mayer to its board. Now with Rigel Pharmaceuticals, Mr Mayer had been in charge of commercial operations at Questcor Pharmaceuticals when it re-launched Acthar gel at a significantly elevated price and turned it into a blockbuster, after acquiring it from Sanofi for small change.
Investors were obviously hoping that Eiger could repeat Questcor’s feat. Perhaps more of them are now asking why other pharma companies were willing to sign over rights to ubenimex, lonafarnib or interferon lambda in the first place.
|Trial name||Trial ID|