BB Biotech and HBMH will take hit on Esperion side-effect scare

BB Biotech and HBMH will take hit on Esperion side-effect scare

BB Biotech (BBB) and HBM Healthcare (HBMH) may have to take a hit on their investments in the US biotech Esperion Therapeutics, which has seen its stock fall by 22% today on the back of results from its second pivotal Phase III study assessing the the cholesterol-lowering effects of its candidate drug bempedoic acid. Although the study met its efficacy objective, what concerned investors was an imbalance in liver function abnormalities and deaths on study that could flag a safety issue.  BB Biotech has 4.5% of its NAV invested in Esperion, while London-listed HBM Healthcare’s holiding is equivalent to 2.7% of its NAV.

Esperion’s study enrolled 2,230 patients with high-risk atherosclerotic cardiovascular disease (ASCVD) who were inadequately controlled with lipid-modifying therapies, including maximally tolerated statins. The 52 week study met its primary endpoint with on-treatment LDL-C lowering of an additional 20% at twelve weeks. Patients treated with bempedoic acid also achieved a significant 22% reduction in high-sensitivity C-reactive protein (hsCRP), an important marker of the underlying inflammation associated with cardiovascular disease. The incidences of adverse events were similar (treatment 78.5% vs placebo 78.7%) as were the rates of serious adverse events (14.5% vs. 14.0%). However, there was a numerical difference in fatal adverse events not related to study drug: 13 (0.9%) in the treatment group compared to two (0.3%) on control.

Esperion had earlier reported results from a Phase III trial (study 4, or 1002-048) in 269 patients with ASCVD or at high risk for ASCVD who have high LDL cholesterol levels (100 mg/dl or greater) despite treatment with ezetimibe with or without a low starting dose of a statin. This study met its primary endpoint at 12 weeks, showing a significant reduction in LDL levels in the bempedoic acid group. LDL cholesterol was reduced by 23% vs an increase of 5% on placebo, resulting in a 28% difference between the groups. There was a significant reduction of 32% in hsCRP.

Over the next few months, Esperion expects to report results from its three remaining pivotal Phase III studies of bempedoic acid and or bempedoic acid/ezetimibe. later this month, it may reprot the outcome of a Phase III study in patients with low or no background statin therapy, to be followed by a bridging study to support bempedoic acid/ezetimibe in August. A 52-week study in ASCVD and/or HeFH on background of maximally tolerated statins (Study 2) is expected to report in September.

The company aims to file for approval in early 2019 and hopes to establish a new once-daily oral therapy for hypercholesterolaemia at a lower price point than Praluent and Repatha, the injectable PCSK9 antibodies from Regeneron/Sanofi and Amgen. By coincidence, Regeneron and Sanofi have just announced plans to cut substantially the price of their drug in exchange for exclusive coverage in Express Scripts national formulary, a move that ill almost certainly set off a new round of price cutting in this market (see separate story on Quoteddate.com).

Esperion has previously reported a Phase II trial (n=58) evaluating bempedoic acid added to PCSK9 antibodies and showed a placebo adjusted 30% LDL lowering, which was consistent with that seen from other non-statin studies (-27% vs. +3% placebo) at eight weeks. However, the company has not – as yet – considered further development of this particular combination.

 

BB Biotech and HBMH will take hit on Esperion side-effect scare