Dive Brief:
- The third bempedoic acid Phase 3 study has hit its primary endpoint, according to developer Esperion, with a 23% fall in LDL cholesterol (the so-called 'bad' cholesterol) at 12 weeks in high-risk, statin-intolerant patients, compared with 1% in the placebo group.
- Patients also saw a 25% fall in hsCRP, an inflammation biomarker, compared with a 2% increase in the placebo group.
- Esperion is expecting data from two more pivotal trials in August and September 2018. A New Drug Application submission is planned for the monotherapy and combination therapy no later than the first quarter 2019.
Dive Insight:
The results are the third of five pivotal studies to read out for the treatment, in development alone or in combination with ezetimibe as a complementary once-daily oral treatment option for patients with atherosclerotic cardiovascular disease (ASCVD), or at a high risk for ASCVD, and who are in need of additional LDL-cholesterol lowering.
"The dataset from this study is reassuring and highly consistent with what we’ve seen previously with bempedoic acid," said Ulrich Laufs, member of Esperion’s Phase 3 executive committee and director of the Department of Cardiology, at Leipzig University.
Cholesterol lowering drugs fall largely into two camps at the moment. The low-cost statins, many of which are now generic, that are given to the vast majority of patients who need to lower their blood lipids, and the high-cost injectable PCSK9 inhibitors, indicated for patients on maximum dose statins. Esperion is aiming at a market in between the two.
"The combination of bempedoic acid and ezetimibe in a single pill is our lead product, but we are also developing bempedoic acid as a monotherapy," said Experion's CEO Tim Mayleben in an interview with BioPharma Dive. "Physicians are constantly trying to tailor therapies to their patients. They have access to seven statins, generic ezetimibe and the injectable PCSK9 inhibitors, but they still don't have enough tools to lower LDL cholesterol. Our once-daily oral bempedoic acid monotherapy and bempedoic acid and ezetimibe combination could fill the void."
"We don't see the PCSK9 inhibitors as competitors," Mayleben added. "The people who need these should be able to get them, for example those who have had several cardiovascular events despite being on maximal statin therapy, or many of those with heterozygous familial hypercholesterolemia."
One of the biggest challenges for new drugs into this category is cost. Payers have balked at the multi-thousand dollar price tags of the PCSK9 inhibitors.
"We have considered the pricing point for our drugs, and we plan to price responsibly for the long term. We will price the way that branded oral LDL cholesterol drugs have traditionally been priced, that is around $9 to $10 a day, or around $3500 wholesale acquisition cost. We believe that it is important that they are affordable," said Mayleben. "Accessible is also important – for PCSK9 inhibitors, the challenge isn't just the price. Many patients don’t like injectable therapies."
The patient deaths reported earlier this month have cast a shadow over the late stage clinical trials, but Mayleben said he is upbeat about the drug's future, with data due to readout for the bempedoic acid and ezetimibe combination pill in late August.
"The data monitoring committee has looked very closely at the unblinded data from the previous study and is very confident that the deaths are not related to the study treatment," he said. "We are in very good shape and have met all the timelines for our clinical trials. We will have data for all five pivotal studies by September, and will submit an NDA for both the monotherapy and combination therapy no later than the first quarter of 2019. We could see a launch in the first quarter of 2020."
Correction: A previous version of this article misidentified when Esperion plans to file its New Drug Application.