|Gemphire Announces Plans to Advance Gemcabene into Phase 3 Clinical Development|
New analysis of data shows clinically meaningful reductions in LDL-C and hsCRP across multiple trials and confirms support to advance gemcabene into Phase 3
End of Phase 2 meetings planned for early 2018
ROYAL-1 study accepted for presentation at AHA Scientific Sessions in
COBALT-1 study to be presented at the FH Foundation’s Summit meeting on
Conference call at
Gemphire is developing gemcabene as an add-on therapy to diet and maximally-tolerated statins for the treatment of several hypercholesterolemic populations, including atherosclerotic cardiovascular disease (ASCVD), with an emphasis on the high risk cardiometabolic subset of ASCVD patients, heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH). The Company also plans to develop gemcabene as monotherapy or as add-on therapy to diet and other lipid lowering therapies for the treatment of severe hypertriglyceridemia (SHTG). Gemcabene has been shown to be safe and effective in combination with all current treatments for hypercholesterolemia, including the highest intensity statins, PCSK9 inhibitors and ezetimibe.
“I believe we have accumulated a compelling body of clinical data demonstrating the ability of gemcabene to reduce low density lipoprotein cholesterol (LDL-C) in both orphan and broad dyslipidemic conditions,” said Dr. Steven Gullans, Interim CEO of Gemphire. “Gemcabene is a unique late stage clinical asset and the only compound in development across the full spectrum of dyslipidemia that targets the triple threat of LDL-C, inflammation and triglycerides (TG). We look forward to reviewing these data with the
“Many high-risk patients are unable to achieve optimal LDL-C reductions and levels with the currently available therapies,” said
New Analysis Shows That 600 mg of Gemcabene Reduced LDL-C by 21% in Hypercholesterolemic Patients and by 25% in Mixed Dyslipidemic Patients across Multiple Clinical Trials
The Company has performed an extensive analysis of data on hypercholesterolemic patients across previously completed clinical trials for gemcabene, including the most recently completed COBALT-1 and ROYAL-1 studies. In addition to the LDL-C reduction in the overall cohorts, efficacy was assessed according to baseline LDL-C levels, and other baseline characteristics, such as the degree of obesity, magnitude of HbA1c, mixed dyslipidemia, level of inflammation, a responder analysis and combinations of these factors.
Data for the ROYAL-1 study have been accepted for presentation at the American Heart Association’s (AHA) Scientific Sessions in
Patients were included in the combined analysis if they were hypercholesterolemic and were on stable statin and/or other lipid lowering therapy, which represents the intended use for gemcabene in clinical practice for its hypercholesterolemic indications. The prior clinical trials included 352 hypercholesterolemic patients, composed of placebo (n=110) and gemcabene 150 mg (n=23), 300 mg (n=61), 600 mg (n=94) and 900 mg (n=64) dose groups. Data from the gemcabene 600 mg dose group are presented in the table below since this is the intended target dose for the Phase 3 trials for the reduction of LDL-C across the hypercholesterolemic patient population.
Gemphire believes gemcabene offers a unique value proposition for those patients with a high-risk cardiometabolic profile, specifically those with obesity, pre-diabetes /diabetes, inflammation and/or mixed dyslipidemia. Mixed dyslipidemia refers to a group of patients at high risk for cardiovascular disease that have elevated LDL-C, apolipoprotein B, and TGs. Cardiovascular demographics from the
Ability of Gemcabene to Reduce hsCRP and Inflammation is Potentially a Key Differentiator
Elevated serum C-Reactive Protein (hsCRP) is a known biomarker for patients at increased risk of a cardiovascular event. As reported previously in the ROYAL-1 study, 600 mg of gemcabene lowered serum hsCRP by 40% (n=51) compared to 6% for placebo (n=51) (p<0.0001). Note that this effect was additive to the reduction of hsCRP provided by statins, as the ROYAL-1 patients were already taking maximally tolerated doses of statins. From the combined analysis in hypercholesterolemic patients the median hsCRP reduction for patients on gemcabene 600 mg was 40% (n=90) compared with 5% in the placebo group (n=108) (p<0.0001).
CRP is a plasma protein biomarker secreted into the blood from the liver in response to inflammation. Reducing this biomarker is associated with a reduction in cardiovascular risk, as confirmed by Novartis Inc.’s Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) recently presented at the
Gemcabene Appears Safe for High Risk Patients in Combination with Maximally Tolerated Statins and Other Approved Treatments
The COBALT-1 and ROYAL-1 trials were designed to determine the safety, tolerability and efficacy of gemcabene as an add-on to the highest doses of statins (e.g., rosuvastatin 20 and 40 mg and atorvastatin 40 and 80 mg doses; moderate intensity therapies were also included), as well as PCSK9 inhibitors, and ezetimibe.
We believe the results from all 20 clinical studies in which 956 patients were exposed to gemcabene have demonstrated that gemcabene is well tolerated and safe. Although in practice, most patients are on low and moderate intensity statins, in our clinical trials gemcabene demonstrated a clean safety profile even when combined with the highest doses of the high intensity statins, simvastatin, atorvastatin and rosuvastatin. To date, there has been no evidence for hepatic or muscle related toxicities and no serious adverse events related to gemcabene treatment. Overall treatment emergent adverse events for gemcabene have been similar to placebo. Most adverse events have been mild to moderate in intensity and the most commonly reported adverse events have been infection and headache (based on occurrence in > 5% of subjects on gemcabene, although the rate for infection was less than placebo).
Gemphire’s Commitment to Cardiometabolic Patients, Physicians and Payors
Cardiovascular disease remains the leading cause of death globally despite the availability of statins and other therapeutics. In addition, the large recent increases in the prevalence of obesity and diabetes will result in a much greater number of individuals at risk for cardiovascular and liver diseases, including NASH. The highest risk patients would benefit from a new therapy that can be added safely to all commonly prescribed statins at any dose. Gemcabene has been given to over 950 patients to date and it appears to be a safe and effective therapeutic option for millions of cardiometabolic patients who are already on maximally-tolerated statins to reduce LDL-C, hsCRP and other potentially atherogenic lipid particles. As a once daily oral therapy at an affordable price point, gemcabene has the potential to be a valuable new approach that will provide benefits to patients, physicians and payors.
“Gemcabene has demonstrated efficacy across a broad array of important lipid parameters, such as LDL-C, non-HDL-C, total cholesterol, apolipoprotein B and triglycerides, that have been associated with cardiovascular events, such as heart attacks, stroke and death. Gemcabene has also demonstrated significant effects on reducing hsCRP, a marker of inflammation, which may be an important new target of therapy in patients with cardiovascular disease, based on the CANTOS trial results. Importantly, gemcabene has demonstrated an excellent safety profile without evidence of hepatic or muscle toxicities, even when combined with the most potent statins,” stated Dr. Lee Golden, Chief Medical Officer of Gemphire.
COBALT-1 study to be presented at the FH Foundation’s Summit
Gemphire will also be announcing full results of the COBALT-1 (HoFH) study at the FH Foundation’s Summit meeting in
Gemphire to Soon Launch Proof of Concept Program in NASH
As previously announced, Gemphire will be initiating its proof of concept study in patients that suffer from fatty liver disease and nonalcoholic steatohepatitis (NASH) in the fourth quarter of 2017. Unmanaged cardiometabolic disease is the underlying cause of atherosclerosis and fatty liver disease. Gemcabene’s unique mechanism of action has demonstrated positive attributes that may be protective to both the heart and liver. Approximately 6 million patients in the U.S. are affected by NASH for which there is currently no effective treatment available.
Conference Call and Webcast
Gemphire management will host a conference call for investors at
Gemcabene’s Mechanism of Action and Safety Profile Are Highly Differentiated
Gemphire’s product candidate, gemcabene (CI-1027), is a first-in-class, once-daily, oral therapy that may be suitable for patients who are unable to achieve normal levels of LDL-C or triglycerides with currently approved therapies, primarily statins. Gemcabene's mechanism of action is designed to enhance the clearance of very low-density lipoproteins (VLDLs) in the plasma and inhibition of the production of cholesterol and triglycerides in the liver. The combined effect for these mechanisms has been clinically observed to result in a reduction of plasma non-HDL-C, VLDL-C, LDL-C, apolipoprotein B and triglycerides. In addition, gemcabene has been shown to markedly lower C-reactive protein and improve insulin sensitization. Gemcabene is liver-directed and reduces apoC-III mRNA and plasma levels. Gemcabene also reduces acetyl-CoA carboxylase (ACC1) and CCR2/CCR5 receptor mRNA levels, which may have applications in non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD). Gemcabene has demonstrated proof of concept efficacy for NASH in the STAM™ model developed at
Gemphire is a clinical-stage biopharmaceutical company that is committed to helping patients with cardiometabolic disorders, including dyslipidemia and NASH. The Company is focused on providing new treatment options for cardiometabolic diseases through its complementary, convenient, cost-effective product candidate gemcabene as add-on to the standard of care especially statins that will benefit patients, physicians, and payors. Gemphire has initiated 3 clinical trials for homozygous familial hypercholesterolemia (HoFH), heterozygous familial hypercholesterolemia (HeFH)/atherosclerotic cardiovascular disease (ASCVD), and severe hypertriglyceridemia (SHTG) under NCT02722408, NCT02634151, and NCT02944383, respectively with a fourth planned trial in NASH to initiate in second half of 2017. Please visit www.gemphire.com for more information.
Forward Looking Statements
Any statements in this press release about Gemphire’s future expectations, plans and prospects, including statements about Gemphire’s financial prospects, future operations and sufficiency of funds for future operations, clinical development of Gemphire’s product candidate, expectations regarding future clinical trials, regulatory submissions and meetings and future expectations and plans and prospects for Gemphire, expectations regarding operating expenses and cash used in operations, and other statements containing the words "believes," "anticipates," "estimates," "expects," "intends," "plans," "predicts," "projects," "targets," "may," "potential," "will," "would," "could," "should," "continue," “scheduled” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the success and timing of Gemphire’s regulatory submissions and pre-clinical and clinical trials; regulatory requirements or developments; changes to Gemphire’s clinical trial designs and regulatory pathways; changes in Gemphire’s capital resource requirements; Gemphire’s ability to obtain additional financing; Gemphire’s ability to successfully market and distribute its product candidate, if approved; Gemphire’s ability to obtain and maintain its intellectual property protection; and other factors discussed in the "Risk Factors" section of Gemphire’s Annual Report on Form 10-K for the year ended