5) Maacy Traning Module-Product Knowledge.pptx

Product Knowledge of Maacy What is Maacy Macitentan is used to manage the symptoms of pulmonary arterial hypertension (PAH; high blood pressure in the vessels that carry blood to the lungs). Macitentan is in a class of medications called endothelin receptor antagonists. It works by stopping the a...

Product Knowledge of Maacy What is Maacy Macitentan is used to manage the symptoms of pulmonary arterial hypertension (PAH; high blood pressure in the vessels that carry blood to the lungs). Macitentan is in a class of medications called endothelin receptor antagonists. It works by stopping the action of endothelin, a natural substance that causes blood vessels to narrow and prevents normal blood flow in people who have PAH. Maacy Approved Indication is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to reduce the risks of disease progression and hospitalization for PAH. Maacy dose strength 10 MG once daily Maacy Mechanism Of action • • • • • • • • Macitentan selectively inhibits the binding of endothelin-1 (ET-1) to ETA and ETB receptors. By inhibiting the effects of elevated ET-1 levels, ERAs reduce vasoconstriction, smooth muscle cell proliferation, and pulmonary vessel fibrosis. Endothelin (ET) is an extremely potent blood vessel constricting substance that is secreted by endothelial cells. In the lungs, the most common ET form released is ET-1. ET-1 release can occur through both constitutive and non-constitutive pathways. Upon release, ET-1 can bind to the ET receptors that are expressed on arterial smooth muscle cells and fibroblasts in the lungs. Blocking of the ETA receptor subtype seems to be of more importance in the treatment of PAH than blocking of ETB. Likely because there are higher numbers of ETA receptors than ETB receptors in pulmonary arterial smooth muscle cells. Maacy Pharmacokinetics: Absorption and Distribution  The Cmax reached within 8 Hours.  Metabolism: Hepatic (CYP3A4, 2C19).  Elimination: route is Renal & Fecal.  Distribution: Macitentan bound to human plasma proteins >99%.  Terminal half-life estimates of Macitentan averagely 17 hours.  Macitentan is proposed to be taken with or without food. Maacy Clinical trials Maacy Clinical trial overview Description Patient Population Treatment group SERAPHIN Study • A 15 month, multicenter, double‐blind, parallel‐group study, placebocontrolled, event-driven. • A total of 742 patients aged from 12 years and older randomized in parallel groups 1:1:1 . • • • One group takes Placebo only Second group takes 3mg Macitentan once daily Third group takes 10mg Macitentan once daily SERAPHIN OP EXTENSION Study • A 9‐year, multicenter.(Survival study) • A 36 Month multicenter, double‐blind, parallel‐group study, placebocontrolled, event-driven. (Combination therapy) • A total of 550 patients aged from 12 years and older divided between two study groups: • First group: 242 patients in the survival study. • Second group: 306 patients in the study of the combinational therapy with Macitentan • • Patients were randomized 1 group receiving Macitentan to study the survival rate. The other part were randomized I 2 parallel groups 1:1, one group is taking placebo + background therapy and the second group receiving Macitentan + background therapy Clinical trial overview Seraphin Study A 15 month, multicenter, double‐blind, parallel‐group study, placebo-controlled, event-driven, A total of 742 patients aged from 12 years and older randomized in parallel groups 1:1:1, One group takes Placebo only, Second group takes 3mg Macitentan once daily, Third group takes 10mg Macitentan once daily. Seraphin Study Randomization • We randomly assigned patients with symptomatic pulmonary arterial hypertension to receive  Placebo once daily.  Macitentan at a once-daily dose of 3 mg.  Macitentan at a once-daily dose of 10 mg. Seraphin Study Design Stratified, randomized, double-blind, parallelgroupnumber studyof patients recruited in a trial on Largest PAH ever 242 742 Patients 250 250 Seraphin Study inclusion criteria Inclusion Criteria:  Patients 12 years of age or older  Idiopathic (IPAH);  Familial (FPAH)  PAH related to:  Collagen vascular disease;  Simple, congenital systemic-to-pulmonary shunts at least 1 year post surgical repair;  Human immunodeficiency virus (HIV) infection; or  Drugs and toxins.  Confirmation of pulmonary arterial hypertension with the use of right heart catheterization was required.  6-minute walk distance (6MWD) >= 50 m.  Patients with symptomatic pulmonary arterial hypertension (PAH) in modified World Health Organization (WHO) functional class II to IV. Seraphin Study Objective Objectives: Primary Outcome Seraphin Study Objective Objectives: Secondary Outcome  Change from baseline to month 6 in the 6-minute walk distance  The percentage of patients with an improvement in WHO functional class at month 6,  Death due to pulmonary arterial hypertension or hospitalization for pulmonary arterial hypertension up to the end of treatment  Death from any cause up to the end of treatment and up to the end of the study.  Safety end points included adverse events and laboratory abnormalities. Seraphin Study Outcome Effect of Macitentan on the Composite Primary End Point of a First Event Related to Pulmonary Arterial Hypertension or Death from Any Cause. • Primary Outcome:  Macitentan significantly reduced the risk of the first morbidity and mortality event by 45% Seraphin Study Outcome • Secondary Outcome:  Macitentan significantly reduced death due to PAH or hospitalization by 50% Seraphin Study Outcome • Secondary Outcome: Exercise capacity  At month 6, the 6-minute walk distance had decreased by a mean of 9.4 m in the placebo group.  At month 6, the 6-minute walk distance had increased by a mean of 12.5 m in the group that received 10 mg of Macitentan (treatment effect with 10-mg dose vs. placebo, 22.0 m) Macitentan significantly increased the 6-minute walk distance by 22 Meter vs placebo. Seraphin Study Outcome • Secondary Outcome: Change to the baseline to month 6 in WHO FC  Patients on Macitentan 10mg had greater chance to improve FC Status by 74% Seraphin Study Conclusion • Conclusion:  Macitentan significantly reduced the risk of the first morbidity and mortality event by 45%  Macitentan significantly reduced death due to PAH or hospitalization by 50%  Macitentan significantly increased the 6-minute walk distance by 22 Meter vs placebo.  Patients on Macitentan 10mg had greater chance to improve FC Status by 74% Clinical trial overview Seraphin OL Extension Study A 9‐year, multicenter.(Survival study), A 36 Month multicenter, double‐blind, parallel‐group study, placebo-controlled, event-driven. (Combination therapy, A total of 550 patients aged from 12 years and older divided between two study groups: First group: 242 patients in the survival study, Second group: 306 patients in the study of the combinational therapy with Macitentan Seraphine OL Extension Study Design Long-term safety/survival set (n=242) 742 patients 250 Patient Seraphin OL Serap hin 242 Patient 250 Patient Randomized to Macitentan 10 mg Randomized to Macitentan 3 mg Randomized to Placebo 182 entered the OL and received Macitentan 10 MG 185 entered the OL and initiated Macitentan 10 MG 183 entered the OL and initiated Macitentan 10 MG Prematurely discontinued study (n=94) Due to: • Death (56) • Adverse event (16) • Admin (14) • Withdrawal of treatment (6) • Lost to follow (1) • Withdrawal of consent (1) 88 Patient Completed OL Study drug OL Safety Set (n=550) Prematurely discontinued study (n=97) Due to: • Death (50) • Adverse event (19) • Admin (15) • Withdrawal of treatment (6) • Lost to follow (3) • Withdrawal of consent (1) • Use of forbidden drug (1) 88 Patient • Unknown reason (2) Completed OL Study drug Prematurely discontinued study (n=81) Due to: • Death (37) • Adverse event (29) • Admin (11) • Withdrawal of treatment (1) • Withdrawal of consent (2) • Treatment failure (1) 102 Patient Completed OL Study drug Concept Study Objective Objectives:  Long-term data in PAH SERAPHIN Open-Label Extension for Survival Rate  Macitentan in Pulmonary Arterial Hypertension: A Focus on Combination Therapy in the SERAPHIN Open-Label Extension Trial. Seraphin OL Extension Study Outcome (Survival rate) • The Use of Macitentan offers averagely • Estimates of survival at 1, 3, 5, 7 and 9 years were 95%, 84%, 73%, 63% and 53%, respectively. • The median followup time was 5.9 years. 5.9 years of survival. Seraphine OL Extension Study Outcome • Primary Outcome:  Macitentan 10mg combination therapy decreases the rate 38% events by more than placebo combination with background therapy Primary Seraphine OL Extension Study Secondary Outcome • Secondary Outcome:  Patients receiving the Macitentan 10mg combination therapy had a reduction in the risk of 37.4% being hospitalized for PAH of  Patients receiving the Macitentan 10mg combination therapy had a increase in the 6-Minute Walk Distance by 17.9M vs a decrease by 7.8M in the placebo combination therapy Macitentan combination therapy significantly increased the 6-minute walk distance by Meter vs placebo combination therapy 25.9 Seraphin OL Extension Study Conclusion Timely initiation of combination therapy has the potential to increase the likelihood of achieving a low risk status in PAH and thereby improve patient outcomes:  The Use of Macitentan 10mg offers averagely 5.9 years of survival.  Patients receiving the Macitentan 10mg combination therapy had a reduction in the risk of being hospitalized for PAH of 37.4%  Macitentan 10mg combination therapy significantly increased the 6-minute walk distance by 25.9 Meter vs placebo combination therapy Maacy Market Understanding C6B PULMONARY ARTERIAL HYPERTENSION (PAH) PRODUCTS Total Market Total PAH  In term of volume the PULMONARY ARTERIAL HYPERTENSION (PAH) 1.8 % PRODUCTS was operating by 17,232 units with growth 1.8% YOY2022.  In term of value the PULMONARY ARTERIAL HYPERTENSION (PAH) PRODUCTS was operating by 119,031,725 TND MS 2022 19. 4 SAR with growth 9.8% YOY2022  Only dominated by the TND market by 100%  The public sector is growing by 1.8% YOY2022 42. 8 5.5 25. 7 16,924 17,232 2021 Units 2022 Units ERA PRA 6.5 PDE-5i Riociguat  The molecules included:  ERA (Endothelin Receptor Antagonist) growing by 22.3% YOY2022  PDE-5i (Phosphodiesterase-5 Inhibitor) declining by 39.4% YOY2022  PCA (Prostacyclin Analogue) growing by 36.2% YOY2022  PRA (Prostacyclin Receptor Agonist) growing by 10.3% YOY2022  Riociguat growing by 34.3% YOY2022 ERA PDE-5i PCA 36.2 % 39.4 % 22.3 % Riociguat PRA 10.3 % 34.3 % 6,035 7,380 1,853 1,123 3,249 4,425 864 953 2021 Units 2022 Units 2021 Units 2022 Units 2021 Units 2022 Units 2021 Units 2022 Units 2,495 3,351 2021 Units 2022 Units PCA ERA Total Market Total PAH ERA Macitentan Bosentan Ambrisentan 2021 Units 2022 Units GR 2022 MS 2021 MS 2022 16,924 6,035 3,497 2,492 46 17,232 7,380 4,933 1,621 2 22 41 -35 1,696 36 58 41 1 43 67 22 11 826 ?  PULMONARY ARTERIAL HYPERTENSION (PAH) PRODUCTS operating by units with growth 1.8% YOY2022.  The ERA market is operating by 6,035 units with 17,232 growth 22% YOY2022 and MS 43% .  The ERA market have 3 main molecules 22 % 11.2 21.0 66.8 Macitetan Ambrisentan Bosentan Macitetan  Macitentan  Bosentan  Ambrisentan  Leaded By Macitentan which is operating by 3,497 units with growth 41% YOY2022 and MS 67%.  The Second molecule is Bosentan which is operating by 2,492 units with decline 35% YOY2022 and MS 22%.  The growth and MS of Ambrisentan is question mark, with no reason.  This total units of ERA molecules with consideration of the dosage regimen for each molecule gives us an indication that the number pf patients with PAH were 503 Ambrisentan patient in 2021 and increased to 615 patient in 2022 1,696% 46 826 2021 Units 2022 Units ERA MS 2022 6,035 7,380 2021 Units 2022 Units Bosentan 41 % 35 % 3,497 4,933 2,492 1,621 2021 Units 2022 Units 2021 Units 2022 Units Macitentan Total MS 2022 % 2021 Units 2022 Units GR 2022 MS 2021 MS 2022 ERA 6,035 7,380 22 36 43 Macitetan 3,497 4,933 41 58 67 Opsumit 3,130 2,777 -11 90 56 Maacy 367 2,156 487 10 44 44 56 Opsumit Opsumit Maacy Maacy 2,156 -11% 487 % 367 2021 Units 2022 Units 3,130 2,777 2021 Units 2022 Units  From the reading of the ERA market, the main contributing molecule is  Macitentan market is represented by two products: Macitentan by 67% MS. 56% MS with 2,777 unit & declining by -11%  Maacy (Sudair) which is representing 44% MS in the 1st year with 2,156 unit & growing by 487%  Opsumit (J&J) brand which is representing     The growth of the market is leaded by the growth and the introduction of the Maacy as the 1st generic According to the growth of units gives indication that the number of patients on Macitentan molecule increased New product is registered in 2023 but still not available in the market (Macimit) This introduction may affect the MS of Maacy and the brand. Bosentan Market MS 2022 % 2021 Units 2022 Units GR 2022 MS 2021 MS 2022 ERA 6,035 7,380 22 36 43 Bosentan 2,492 1,621 -35 41 22 TRACLEER 2,325 187 -92 93 12 BOSENTOR 167 1,434 759 7 88 12 88 TRACLEER Bosentan BOSENTOR TRACLEER BOSENTOR 2,325 1,434 -35% -92% 759% 187 2,492 1,621 2021 Units 2022 Units 2021 Units 2022 Units 167 2021 Units 2022 Units  The Bosentan Molecule is overall is represented by 1,621 unit, loosing MS by 19% and declining by -35% YOY2022  This lost is represented by the gain in MS of Macitentan, this reflect the reality of current usage as HCPs shifts patient to Macitentan as more safer and effective molecule.  The Bosentan Molecule is divided between:  Tracleer (J&J) the brand which is represented by 187 unit, loosing MS by 81% and declining by -92%.  Bosentor (Pharma science) the 1st generic which is represented by 1,434 unit, gaining MS by 81% and growing by 759%.  This shift gives indication that when a generic enters the market with more affordable price it gains MS as the PAH patient Ambrisentan Market MS 2022 2021 Units 2022 Units GR 2022 MS 2021 MS 2022 ERA 6,035 7,380 22 36 43 Ambrisentan 46 826 1,696 1 11 11.2 21.0 66.8 Ambrisentan 826 1,696% 46 2021 Units 2022 Units  The Ambrisentan Molecule is overall is represented by one product (VOLIBRIS GSK).  In term of units it is represented by 826 unit, gaining 10% MS and growing by 1,696%  This increase is not justified, as all HCPs feedback have no patients on Ambrisentan as it is old molecule with safety issues. Macitetan Ambrisentan Bosentan ERA Market conclusion  The ERA market is the only molecules that can give you indication about the number of PAH patients in KSA and what is the increase every year.  In 2021 the averagely the number of patients were 503 and in 2022 averagely reached to 615 with growth 22%.  This gives us indication that the prevalence in increasing by 7%-10% which is matching to the HCPs feedback.  The main molecule in ERA is Macitentan as it represent 67% MS and is growing vs the decline of Bosentan.  Macitentan is splitted between two Products the brand (Opsumit) and the generic (Maacy).  The brand is owned by J&J which have a very big promotional effort behind it although Maacy is gaining MS. Maacy Competitor Landscape & KM Endothelin Receptor Antagonist (ERA) Macitentan Product 1: • Opsumit Manufacturer: • EXCELLA GmbH & Co. KG (Johnson & Johnson) Doses: • 10 MG Dosage Form: • 30 Tablets Price: • 8,960.65 SAR Product 2: • Maacy Manufacturer: • Sudair Pharma Doses: • 10 MG Dosage Form: • 30 Tablets Price: • 6,272.45 SAR Product 3: • Macimit Manufacturer: • Aizant Drug Research Solutions (Pharma Pharmaceutical industry) Doses: • 10 MG Dosage Form: • 30 Tablets Price: • 5,824.40 SAR Maacy (Break the chain-empowering journey) Patients Using Macitentan vs placebo Seraphin Study Seraphin Study Macitentan significantly reduced the risk of the first morbidity and mortality event Macitentan significantl y reduced death due to PAH or hospitaliza tion by 45% Macitentan significantly by increased the 6-minute walk distance by 22 Meter 50% vs placebo. Patients on Macitentan 10mg had greater chance to improve FC Status by 74% Macitentan in combination with PDE-5i vs placebo in Patients using combination with PDE-5i Seraphin OL extension Study The Use of Macitentan 10mg offers averagely Seraphin OL extension Study Macitentan 10mg combination therapy significantly increased the 6-minute walk 5.9 years of survival. distance by Meter 25.9 vs placebo combination therapy Patients receiving the Macitentan 10mg combination therapy had a reduction in the risk of being hospitalized for PAH of 37.4% Thank You