AMYT.L Regulatory News (AMYT)

27 April 2017

AIM: AMYT

ESM: AYP

Amryt Pharma plc

("Amryt" or the "Company")

Study Results of 'Real-World' Experience of Lojuxta (lomitapide)

Shows Improved Efficacy

Over Clinical Trials of the Drug

Amryt, the pharmaceutical company focused on best-in-class treatments for rare and orphan diseases, is pleased to announce the publication of study results which evaluated the benefits of Lojuxta (lomitapide) in the treatment of Homozygous Familial Hypercholesterolaemia ("HoFH"), a rare, life-threatening disease, which impairs the body's ability to remove LDL cholesterol ("bad" cholesterol) from the blood. The study results confirmed that 'real-world' experience of a cohort of Italian patients show that Lojuxta is a very powerful cholesterol-lowering agent and, in particular, achieved greater efficacy than clinical trials of the drug. Most notably, the study showed that Lojuxta delivered higher reductions in LDL cholesterol ("LDL-C") than can currently be achieved with any other therapeutic options. Lojuxta is an MTP inhibitor approved for adjunctive treatment in adult patients with HoFH and was in-licenced by Amryt in early December 2016. Amryt's exclusive licence covers the European Economic Area ("EEA"), Middle East and North Africa ("MENA"), Turkey and Israel.

The study results have been presented in a paper entitled, "Efficacy of Lomitapide in the Treatment of Familial Homozygous Hypercholesterolemia: Results of a Real-World Clinical Experience in Italy", and published by Advances in Therapy, an international, peer-reviewed journal.

The study, by Laura D'Erasmo et al, collected and analysed clinical and biochemical data in 15 HoFH patients who had been treated for at least six months with Lojuxta in addition to lipid-lowering therapies in different Lipid Clinics across Italy. At a mean dose 19 mg/day, (which was substantially lower than that used in the Phase 3 clinical trials), Lojuxta achieved a maximal mean reduction of LDL-C of 76.5%, with 30% of the patients achieving a greater than 90% reduction. Ten of the 15 patients were receiving apheresis at baseline. Apheresis is an invasive procedure to remove LDL-C from the blood stream. Treatment with Lojuxta enabled 80% of the patients to stop apheresis and reduced the frequency by 40% in the remaining 2 patients. The mean LDL-C prior to stopping apheresis was just 38.5mg/dL reduced from a baseline mean of 426 mg/dL. Despite stopping apheresis, the patients achieved the recommended but stringent LDL-C targets levels, with 60% of patients achieving an LDL-C

Prof. Marcello Arca, Sapienza' University of Rome, commented:

"This real-world experience, has shown Lojuxta to be a very powerful and well tolerated cholesterol-lowering agent in patients with HoFH. The reduction in LDL-C that we observed is far higher than seen in clinical trials and higher than we can achieve with any other therapeutic option we have for patients with this difficult to treat and devastating disease. The ability to stop apheresis and still achieve LDL-C target levels in patients who had LDL-C levels up to 8 times the recommended level is remarkable".

Dr Helen Phillips, Head of Medical Affairs at Amryt, commented:

"We are delighted that these data have been published. Physicians used to believe that the LDL-C targets recommended by the European Atherosclerosis Society were impossible to achieve in HoFH but this is no-longer the case.

"These data are not unique to Italy - we have seen similar results in patients treated in Spain, Sweden and Netherlands. Unlike statins, ezetimibe and PCSK-9 inhibitors, Lojuxta works independently of LDL receptors which have little to no functionality in HoFH. Through this different mechanism of action, Lojuxta offers patients with HoFH an ability to reach the LDL-C levels of normal individuals and stop the incredibly burdensome and invasive procedure of apheresis. It offers the potential to transform the lives of patients with HoFH, with the addition of a capsule a day".

Enquiries:

About the Real-World Clinical Study

The study, "Efficacy of Lomitapide in the Treatment of Familial Homozygous Hypercholesterolemia: Results of a Real-World Clinical Experience in Italy" by Laura D'Erasmo et al was published in Advances in Therapy, DOI: 10.1007/s12325-017-0531-x.

A retrospective analysis was performed of 15 adult patients with a genetically confirmed diagnosis of HoFH (10 with mutations in LDLR and 5 in LDLRAP1 gene) who received treatment with lomitapide post reimbursement in Italy. The analysis included data from up to 3 years of treatment with lomitapide. Prior to receiving lomitapide, their median LDL-C level was 426.0 ± 204.0 mg/dL, despite receiving treatment with statins, ezetimibe and apheresis (in 10 of the 15 patients). The addition of lomitapide (average daily dosage of 19 ± 13.3 mg/day) lowered LDL-C levels a mean 68.2 ± 24.8% versus baseline and by 76.5 ± 16.7% at nadir prior to changes in apheresis schedules. At their last visit, 60% of patients showed LDL-CDuring treatment with lomitapide, 8 over 10 patients receiving LA (80%) stopped this treatment due to the pronounced cholesterol reduction. Prior stopping apheresis their LDL-C was a mean nadir 38.5 mg/dL (26.8-151 mg/dL)]. In addition, in the in the 2 remaining patients on apheresis, they reduced their apheresis requirements by 40%. A wide range (43-97%) of individual LDL-C reduction was observed, but this was not related to underlying mutations causing the HoFH.

During follow-up, 53.3% of patients reported at least one episode of diarrhoea, but none was severe; none had persistent liver transaminase >5 X ULN or had to stop treatment due to side effects. During treatment, 6 HoFH patients were also investigated by liver imaging techniques according to the European label showing results well within the normal range. At baseline, only 1 patient out of 5 was referred to have liver steatosis, while at follow-up there were 2 patients with fatty liver.

In this real word experience, lomitapide was confirmed to be an effective cholesterol-lowering agent in HoFH with a good safety profile.

In the Phase 3 clinical trials with lomitapide (published in the lancet by Cuchel et al) which employed a forced titration schedule, the mean LDL-C reduction was 50% at a mean dose of 40mg/day. Ninety-three percent of patients experienced GI adverse effects, reducing to 74% and 21% patients experienced LFTs > 3 x ULN in this 78-week study. The real-world evidence therefore supports a higher level of efficacy at a mean lower dose demonstrating an improved benefit : risk profile than that observed in the clinical trials.

About Amryt Pharma plc

(www.amrytpharma.com)

Amryt Pharma is a specialty pharmaceutical company focused on developing and delivering innovative new treatments to help improve the lives of patients with rare or orphan diseases. The Company is building a diversified portfolio of commercially attractive, best-in-class, proprietary new drugs to help address some of these rare and debilitating illnesses for which there are currently no available treatments.

The Company holds an exclusive licence to sell Lojuxta (lomitapide) for adults, across the EU and other territories including the Middle East, North Africa, Turkey and Israel. Lojuxta is used to treat a rare life-threatening disease called Homozygous Familial Hypercholesterolemia, which impairs the body's ability to remove LDL cholesterol ("bad" cholesterol) from the blood. This typically results in extremely high blood LDL cholesterol levels leading to aggressive and premature narrowing and blocking of arterial blood vessels. If left untreated, heart attack or sudden death may occur in childhood or early adulthood.

Amryt's lead drug candidate, AP101 (Episalvan), is a potential treatment for Epidermolysis Bullosa ("EB"), a rare and distressing genetic skin disorder affecting young children for which there is currently no treatment. It is currently in Phase 3 clinical trials. The global market opportunity for EB is estimated to be in excess of EUR 1.3 billion.

Amryt's earlier stage product AP102 is focused on developing novel, next generation somatostatin analogue ("SSA") peptide medicines for patients with rare neuroendocrine diseases, where there is a high unmet medical need, including acromegaly and Cushing's disease. 

The Company joined AIM and Dublin's ESM in April 2016 following the reverse takeover of Fastnet Equity PLC.