PHM321 - Drug Presentation Master Doc PDF

Beyfortus Drug Names - Nirsevimab Manufacturer - AstraZeneca & Sanofi Mechanism of Action - Binds F protein on respiratory syncytial virus (RSV) → prevents confirmation needed for fusion Indication - RSV prevention: - For all infants and neonates in their first RSV season - For high-risk...

Beyfortus Drug Names - Nirsevimab Manufacturer - AstraZeneca & Sanofi Mechanism of Action - Binds F protein on respiratory syncytial virus (RSV) → prevents confirmation needed for fusion Indication - RSV prevention: - For all infants and neonates in their first RSV season - For high-risk infants up to 24 months old entering their second RSV season Market Opportunity Disease state: rare vs. common? - Common, almost all infants infected by age 2 Administration? (hospital/clinic/self?) - Intramuscular injection by a healthcare professional Line of therapy? - For prevention of RSV; basically first line if taken up Competitors? - Palivizumab - shorter half life!, more injections (once monthly → 4-5 per year), expensive - Only for high risk RSV infants - Emerging - Abrysvo - MK-1654 Unmet Need - Cost, convenience, no current treatment specifically for RSV, indication for infants other than high-risk, Dose + Dosing Considerations - Intramuscular injection once per RSV season (only 1 IM dose required) Key Adverse Events - Injection site reactions, upper respiratory tract infections Reimbursement Status - CADTH: cannot determine cost, de novo evaluation is needed INESS: do not reimburse – re-evaluation in 2024 - NACI review in progress Etc (other important points? - Camzyos Drug Names - Mavacamten Manufacturer - Bristol-Myers-Squibb Mechanism of Action - Reversible inhibitor of cardiac myosin ATPase (helps reduce heart contractility) Reduces actin-myosin cross-bridges Indication - Symptomatic obstructive hypertrophic cardiomyopathy (oHCM) - Left ventricle wall thickens and stiffens (hypertrophy) blocking bloodflow out of aorta - Left ventricular outflow tract (LVOT) becomes obstructed and blood flow to rest of body is reduced Only oHCM therapy that targets underlying pathophysiology, other therapies only relieve symptoms Currently only indicated in adults with NYHA stage 2 to 3 heart-failure Second-line therapy, patient must also be on a BB or non-DHP CCB (verapamil or diltiazem) Market Opportunity Disease state: rare vs. common? - Most common genetic heart disease - 60-70% cases are familial, autosomal dominant - Affects at least 1 in every 500 individuals Administration? (hospital/clinic/self?) - Oral capsule → self-administered - 2.5, 5, 10, 15 mg capsules Line of therapy? - First-line: beta blocker, or verapamil/diltiazem (non-DHP CCB) - Second-line: - Camzyos = add-on to first line therapy if ECG/symptomatic deterioration on monotherapy (not used as monotherapy itself) - Disopyramide has QT-prolonging side effects and CYP side effects; goal to replace disopyramide in standard of care. Indicated if symptoms persist despite optimized 1st line therapy - Third-line: invasive septal reduction therapy (surgery, also only relieves symptoms). Indicated if symptoms persist/worsen despite optimized pharmacotherapy Competitors? - Existing: Current standard of care (BB, CCB, disopyramide) - Emerging: - Aficamten (cardiac myosin inhibitor) by Cytokinetics in Phase III trials (slightly better safety profile) - TN-201 by Tenaya (gene therapy) in Phase I trials - MYK-224 (cardiac myosin inhibitor) by BMS in Phase II trials - MYK-581 (small molecule inhibitor) not yet studied in humans Unmet Need - Another option prior to invasive cardiac surgery to reduce ventricular wall size No current therapies target underlying pathology of HCM (Camzyos does) Dose + Dosing Considerations - 2.5, 5, 10, 15 mg Oral, once daily Key Adverse Events - Induced heart failure due to systolic dysfunction Reimbursement Status - CADTH made recommendation to reimburse if the following criteria are met: - Patient must be under direct care of cardiologist - Significant price reduction (73%) INESSS: reimburse with conditions (reduce cost) pCPA: still under consideration for negotiation - First in class Etc (other important points? Carvykti Drug Names - Ciltacabtagene autoleucel (CAR-T from autologous source) Manufacturer - Janssen/Legend BioTech Mechanism of Action - Use patient’s own T cells, infuse transgene to express chimeric T cell receptor against B-cell maturation antigen, reinfuse, to target/destroy refractory/resistant multiple melanoma cells over sustained period Indication - Market Opportunity For the treatment of adult patients with multiple myeloma, who have received at least three prior lines of therapy, and who are refractory to their last treatment 97% of participants had a clinically significant response. Disease state: rare vs. common? - 13th most prevalent cancer in Canada Administration? (hospital/clinic/self?) - Must be administered within a designated CAR-T site (hospital) Line of therapy? - 4th + Competitors? - Abecma is a direct CAR-T competitor with the same indication, but BiTEs and mAbs (not yet marketed in Canada) - Tecvayli - XPOVIO could also be used - Blenrep - pepxato Unmet Need - Incurable disease, relapse and remission a lot Low survival Low health related QoL Patients want more options Dose + Dosing Considerations - Single infusion Key Adverse Events - High risk of getting an adverse effect (eg. cytokine storm) ICANS (immune effector-cell associated neurotoxicity syndrome) CRS (cytokine release syndrome) Anemia/Neutropenia/thrombocytopenia Reimbursement Status - Received CADTH recommendation with conditions, currently with pCPA for negotiation Limited room for private coverage because in-hospital administration Etc (other important points? - Empaveli Drug Names - Pegcetacoplan Manufacturer - Apellis pharmaceuticals Mechanism of Action - Prevents C3 from splitting into C3a and C3b → impacts complement activation cascade downstream (stops both intravascular and extravascular hemolysis) To stop attack on RBCs - Paroxysmal nocturnal hemoglobinuria (PNH) Indication Market Opportunity Disease state: rare vs. common? - Rare Administration? (hospital/clinic/self?) - Self administered subcutaneous infusion Line of therapy? - 2nd line (after failing C5 inhibitor) Competitors? - Solaris (eculizumab) - Ultomiris (ravulizumab-cwvz): more efficacious than Solaris Unmet Need Only treatment that addresses BOTH intravascular and extravascular hemolysis - C5i (Solria and Ultomiris) only target IVH Dose + Dosing Considerations - Dosed twice weekly Key Adverse Events - Injection site reactions Mild diarrhea Reimbursement Status Etc (other important points? CADTH: recommend reimbursement by public plan if insufficient response or intolerable to C5 inhibitor (Soliris and Ultimiris) - - - Imcivree Drug Names - Setmelanotide/ Imcviree Manufacturer - Rhythm Pharmaceuticals Mechanism of Action - MC4R agonist → reduce hunger, satiety, decreased food intake, and weight loss Indication - Bardet-Biedl Syndrome (BBS) & other genetic obesity in adults and adolescents 6 years and older (clinically and genetically confirmed) Market Opportunity Disease state: rare vs. common? - Rare. 1/100,000 ppl for BBS. Administration? (hospital/clinic/self?) - SubQ Daily dosing at home Line of therapy? - Will be 1st line now (breakthrough drug). Competitors? - Also MC4R agonist. Other competitors are not for genetic obesity. And only symptomatically help with reducing appetite or weight loss - New competitors: LB54640 in development. Vi-0521 (phase 4 trials) - current competitors: setmelanotide, contrave, liraglutide Unmet Need - Coverage by ODB, indication for <12 years old, diagnostic measures of BBS, hunger, targeting mc4R pathway There are no other therapies available that are indicated for the treatment of BBS. Unrelenting hunger, hyperphagia, and obesity are identified by patients as 3 of the most distressing and impactful symptoms of the disease. Dose + Dosing Considerations - 1 mg/day for >18 years, 0.5mg/day for <18 years. Given at the beginning of the day, without regard to meals There is no food requirement for administration No dose adjustments are needed for patients with mild to moderate renal impairment Key Adverse Events - Hyperpigmentation, injection site erythema. Nausea, spontaneous penile erections, vomiting, diarrhea, headache, aggression, fatigue Generally all mild and transient - Reimbursement Status - Etc (other important points? - Conditionally recommended by CADTH for reimbursement in the public drug plan as indicated only if prescribed by endocrinologist or specialist in obesity & cost is reduced for a maximum of 26 week period INESSS - no submission made not yet pCPA negotiated Approved by FDA and EU Livtencity Drug Names - Maribavir Manufacturer - Takeda Pharmaceuticals Mechanism of Action - Antiviral against human cytomegalovirus (CMV) Competitively inhibits the protein kinase activity of the human CMV enzyme pUL97 - Inhibits phosphorylation → inhibits viral DNA replication, viral encapsulation, and nuclear egress of viral capsids Indication - *CADTH: Treatment of adults with post-transplant cytomegalovirus infection/ disease who are refractory (with or without genotypic resistance) to 1 or more prior antiviral therapies Not indicated for pediatrics yet in Canada Market Opportunity Disease state: rare vs. common? - Rare Administration? (hospital/clinic/self?) - Oral medication, so you can take it at home Line of therapy? - 2nd line - 1st line in patients with DNA mutation - So depends on the diagnosis Competitors? - Valganciclovir, ganciclovir, foscarnet, cidofovir, letermovir Unmet Need - Lack of curability of CMV Increased side effects with current treatment regimens (antivirals) Limited options - For patients with DNA mutation, refractory CMV, resistant CMV in pediatrics and adults - No drugs approved for treatment of CMV disease in transplant recipients Dose + Dosing Considerations - Oral medication 400 mg (two 200 mg tablets) twice daily for both adults and children 12 years of age and older weighing at least 77 pounds (35 kg) Key Adverse Events - Taste disturbances, GI effects Reimbursement Status - CADTH: Reimburse with condition: - Adults patients with refractory to 1 or more of valgan, gan, foscarnet, and cidofovir - Subsequent treatment with livtencity in patients who has recurrence of CMV after successful treatment with Livtencity - Prescribed by clinicians with experience in transplant medicine or infectious disease INESS: Reimburse with condition PSP by Taketa: $10000 co-pay Private payers: under Prior authorization - Etc (other important points? - Scemblix Drug Names - Scemblix (asciminib) Manufacturer - Novartis Mechanism of Action - Potently inhibits the kinase activity of BCR ABL1 via allosteric binding Classified as a Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor Indication - Adult patients with Ph+ CML who have received 2 or more prior TKI therapies Market Opportunity Disease state: rare vs. common? - More “rare” type of cancer - Low annual incidence globally Administration? (hospital/clinic/self?) - Self Line of therapy? - Third line therapy Competitors? - Bosutinib - Imatinib - Dasatinib Unmet Need - Limited treatment options for patients who have received 2 or more prior TKIs - Many patients stop first-line therapy due to SEs Adult patients with Ph+ CML in CP who have experienced treatment failure/intolerance to 2 more more prior TKIs Dose + Dosing Considerations - Tablets (20 mg and 40 mg) Key Adverse Events - Thrombocytopenia, neutropenia, headache, diarrhea, nausea Reimbursement Status - Covered by ODB and INESSS under specific clinical circumstances Private insurance companies require special authorization for coverage if specific clinical circumstances are met pCPA negotiation concluded in 2023 Etc (other important points? - CADTH does not represent good value to the health care system at the public list price - Price reduction required Sunlenca Drug Names - Manufacturer - Mechanism of Action - Indication - Market Opportunity Lenacapavir Selectively inhibits HIV-1 capsid function through multiple stages Binds directly to the interface between capsid protein subunits HIV-1 replication is inhibited through the interference of multiple, essential steps present in the viral life cycle Disease state: rare vs. common? Administration? (hospital/clinic/self?) Line of therapy? Competitors? - Unmet Need - Dose + Dosing Considerations - Maintenance injections every 6 months Key Adverse Events - Injection site reactions, nausea Reimbursement Status - Etc (other important points? - Tezspire Drug Names - Tezepelumab Manufacturer - AstraZeneca Mechanism of Action - Human monoclonal antibody that acts on TSLP cytokine, prevents binding to the receptor, thus results in increased bronchodilation Indication Asthma - Had to have gone through the 5 steps of asthma theraepy - Age 12+ - 2 or more clinically relevant exacerbations in past year - Respirologist to give first dose Market Opportunity Disease state: rare vs. common? - Severe asthma uncontrolled despite max. tolerated dose of ICS Administration? (hospital/clinic/self?) - SC injection done by doctor, cannot be self-administered Line of therapy? - Used along with high dose maintenance ICS/LABA for asthma control Competitors? - Reslizumab, benralizumab, mepolizumab, duplimab, omalizumab Unmet Need - Management of symptoms of exacerbations, first in its kind to target non phenotypic asthmatic patients, mixture of eosinophilic and non-eosinophilic inflammation Dose + Dosing Considerations - Subcutaneous Injection every 4 weeks Key Adverse Events - Injection site reactions severe cardiac effects that were found in some patients, but most of those patients already had some sort of cvd initially Reimbursement Status - Reimburse with conditions – Similar to patient journey LOC granted Etc (other important points? - Xpovio Drug Names - Selinexor Manufacturer - Forus Therapeutics Mechanism of Action - inhibits exportin 1 (XPO1), which medicates nuclear export of proteins and RNA. - When inhibited, tumor suppressor proteins accumulate in the nucleus, cell cycle arrest occurs, and oncoproteins are reduced. - Effects induce cancer cell death. - Novel MOA!!! - FIRST IN-CLASS Indication - in combination with (1) bortezomib and (2) dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy Market Opportunity Disease state: rare vs. common? - Multiple myeloma (rare; same as Carvykti!) Administration? (hospital/clinic/self?) - Self administration (oral tablet!) Line of therapy? - Second-line or later (patients must have received at least one prior therapy) Competitors? - Carflizomab, Isatuximab, Daratumumab Unmet Need - lack of curability in multiple myeloma high rate of relapse in multiple myeloma patients (pretty much inevitable) limited treatment options especially beyond first and second line lack of accessible/portable treatment options Dose + Dosing Considerations - Usual dose: 5 x 20 mg tablets on day 1 of each week of 28-day cycle - (= 100 mg once weekly) If intolerable side effects, dose reduced by 20 mg on day 1 (80//60/40 mg weekly) Key Adverse Events - Neutropenia, thrombocytopenia, hyponatremia, anemia, fatigue Nausea, vomiting, diarrhea, anorexia, weight loss Reimbursement Status - CADTH reimbursement of Xpovio is recommended with conditions: - adults with confirmed multiple myeloma, who have received 1 prior therapy. - Renewal requires treatment response and tolerability. - Treatment response must be assessed frequently. - Prescribers must have expertise in multiple myeloma and familiarity with Xpovio’s adverse effect profile. - Xpovio is only to be prescribed and reimbursed in combination with bortezomib and dexamethasone - 93% reduction in price is required. INESSS - refusal of registration Publicly funded in 4 provinces - Alberta, Saskatchewan, Nova Scotia and British Columbia Ontario - available for EAP-eligible patients Etc (other important points? - Standard of care: therapy is composed of a 2-3 drug regimen -> altered as patients become refractory/relapse treatment Zoryve Drug Names - Roflumilast Manufacturer - Arcutis Biotherapeutics Mechanism of Action - Potent inhibitor of PDE-4 → leads to accumulation of cAMP (secondary messenger controlling inflammation) → elevated cAMP activates PKA signaling pathway Indication - Plaque Psoriasis For patients aged 12+ - Including intertriginous areas (folds) Market Opportunity Disease state: rare vs. common? - Common - affects 125 million people worldwide, 900k Canadians - Most common form of psoriasis Administration? (hospital/clinic/self?) - Self-administration Line of therapy? Competitors? - Betamethasone - Calcipotriol - Risankizumab (skyrizi) (biologic) - Secukinumab (cosentyx)(biologic) Unmet Need - No definitive care - no treatment available for intertriginous psoriasis (skin folds) Incomplete response to current therapies - gap in achieving almost clear skin Quest for optimal therapies (Especially in intertriginous areas) Low quality of life for patients - impairs daily activities + mental well-being Dose + Dosing Considerations - Cream - apply Key Adverse Events - Hypersensitivity Topical redness/sensitivity Reimbursement Status - CADTH and INESS recommends public plan reimbursement Not yet on provincial formularies Has private coverage with co-pay requirement Etc (other important points? - First line (and only tx) for genitals and skin folds (intertriginous) First in class Steroid free