New Drugs in Primary Care

2/28/2020

Elizabeth Bald, PharmD, BCACP Assistant Professor (Clinical) University of Utah College of Pharmacy Midwinter Meeting February 29, 2020

Disclosure Learning Objectives

At the conclusion of this activity, pharmacists should be able to Dr. Bald has no actual or potential conflicts of interest to disclose. successfully: 1. Identify therapeutic indications of medications recently approved by the Off-label use of medications will not be discussed during this presentation. U.S. Food and Drug Administration

2. Describe pharmacological properties of new medications

3. Discuss dosing parameters, common adverse effects, and drug interactions of new medications

Learning Objectives oral semaglutide Rybelsus® At the conclusion of this activity, pharmacy technicians should be able to successfully: 1. Recognize names and indications of medications recently approved by the U.S. Food and Drug Administration

2. Identify common adverse effects of new medications

3. Discuss patient access to new medications

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Rybelsus® - Overview Rybelsus® - Overview STARTING DOSE 3 mg MECHANISM OF ACTION ONCE DAILY glucagon-like-peptide-1 receptor agonist 09.20.19 for 30 days glucose-dependent insulin secretion FDA APPROVAL MAINTENANCE DOSES

inappropriate glucagon secretion 7 mg 14 mg type 2 ONCE DAILY ONCE DAILY INDICATION if additional glycemic control is gastric emptying time after 30 days on 3 mg dose diabetes mellitus needed after 30 days of 7 mg

1. Rybelsus (semaglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; September 2019. 1. Rybelsus (semaglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; September 2019. 2. Rybelsus. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. http://micromedex.com/. Accessed January 23, 2020. 2. Rybelsus. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020.

Rybelsus® - Overview Rybelsus® - Overview

stop 2 months before planned pregnancy

0.5 mg 7 or 14 mg 1 mg no no dose adjustment needed ONCE WEEKLY ONCE DAILY ONCE WEEKLY GUIDANCE

no dose adjustment needed begin within 7 days of last injection

1. Rybelsus (semaglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; September 2019. 1. Rybelsus (semaglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; September 2019. 2. Rybelsus. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020. 2. Rybelsus. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020.

Rybelsus® - Administration Rybelsus® - Adverse Effects

COMMON SERIOUS BLACK BOX WARNING TAKE WITH ≤ 4 OZ OF WATER • Nausea (11-20%) • Pancreatitis • Risk of thyroid C-cell • Abdominal pain (10-11%) • Diabetic retinopathy tumors complications WAIT ≥ 30 MINUTES BEFORE EATING, DRINKING, • Diarrhea (9-10%) • Decreased appetite • Acute kidney injury 30 min OR TAKING OTHER ORAL MEDICATIONS (6-9%) • Vomiting (6-8%) • Constipation (5-6%) TAKE ON AN EMPTY STOMACH RIGHT AFTER WAKING UP

1. Rybelsus (semaglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; September 2019. 1. Rybelsus (semaglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; September 2019. 2. Rybelsus. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020. 2. Rybelsus. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020.

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Rybelsus® - Place in Therapy Rybelsus® - Place in Therapy

Population: patients with T2DM ≥ 50 years with established cardiovascular or Population: medication-naïve patients with T2DM chronic kidney disease or ≥ 60 years with cardiovascular risk factors only 1 Comparator: placebo 6 Comparator: placebo

Population: patients with T2DM taking metformin only Population: patients with T2DM taking metformin ± a sulfonylurea 2 Comparator: empagliflozin 7 Comparator: sitagliptin

Population: patients with T2DM taking metformin ± a sulfonylurea Population: patients with T2DM taking basal insulin ± metformin 3 Comparator: sitagliptin 8 Comparator: placebo

Population: patients with T2DM taking metformin ± SGLT2 inhibitor Population: Japanese patients with T2DM taking one antidiabetic medication or treatment with diet/exercise alone 4 Comparator: liraglutide or placebo 9 Comparator: liraglutide or placebo

Population: patients with T2DM, eGFR 30–59 mL/min/1.73 m², taking metformin, a sulfonylurea, or both, or basal insulin ± metformin Population: Japanese patients with T2DM taking one antidiabetic medication PIONEER 5 Comparator: placebo PIONEER 10 Comparator: dulaglutide

3. A quick guide to the PIONEER trials. Medicine Matters diabetes. Published October 2019. Accessed January 27, 2020. 3. A quick guide to the PIONEER trials. Medicine Matters diabetes. Published October 2019. Accessed January 27, 2020.

Rybelsus® - Place in Therapy Rybelsus® - Patient Access

efficacy and safety in moderate renal impairment Commercial Medicaid Medicare

non-inferior cardiovascular safety compared to placebo $10 per month non-preferred; varies by plan with co-pay card PA required superior weight loss compared to liraglutide and empagliflozin

HbA1c reduction of 0.6-1.3%; non-inferior to liraglutide

4. Savings & Support: RYBELSUS® (semaglutide) tablets 7 mg or 14 mg. Product R®. Accessed January 23, 2020. 3. A quick guide to the PIONEER trials. Medicine Matters diabetes. Published October 2019. Accessed January 27, 2020. 5. Preferred Drug List. Utah Department of Health Medicaid. Accessed January 23, 2020.

Rybelsus® - Patient Access Rybelsus® - Patient Access

COVERAGE DETAILS https://www.novocare.com/rybelsus/cost-navigator.html

• For commercially insured patients ≥ 18 years • No monthly coverage limit for first 12 fills through 2/28/2021 • After 12 fills or on 3/1/2021, maximum coverage of $250 per month

4. Savings & Support: RYBELSUS® (semaglutide) tablets 7 mg or 14 mg. Product R®. Accessed January 23, 2020. 4. Savings & Support: RYBELSUS® (semaglutide) tablets 7 mg or 14 mg. Product R®. Accessed January 23, 2020.

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emtricitabine/tenofovir alafenamide Descovy® - Overview Descovy® MECHANISM OF ACTION combination of two nucleoside reverse-transcriptase inhibitors

HIV virus replication

6. Descovy (emtricitabine and tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; December 2019. 7. Descovy. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020.

Descovy® - Overview Descovy® - Overview

09.03.19 DOSING FDA APPROVAL 200 mg 25 mg emtricitabine tenofovir alafenamide

once daily HIV pre-exposure prophylaxis INDICATION in at-risk patients ≥ 35 kg excluding receptive vaginal sex

6. Descovy (emtricitabine and tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; December 2019. 8. TAF Component of DESCOVY FOR PrEP™. HCP. https://www.descovyhcp.com/taf-pharmacology#. Accessed January 27, 2020. 7. Descovy. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020.

Descovy® - Overview Descovy® - Administration

crosses placenta but no evidence of harm TAKE WITH OR WITHOUT FOOD

STORE IN ORIGINAL CONTAINER not studied in severe hepatic impairment

DO NOT CRUSH OR SPLIT TABLETS not recommended with CrCl <30 mL/min

6. Descovy (emtricitabine and tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; December 2019. 6. Descovy (emtricitabine and tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; December 2019. 7. Descovy. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020. 7. Descovy. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020.

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Descovy® - Adverse Effects Descovy® - Place in Therapy

COMMON SERIOUS BLACK BOX WARNING

• Diarrhea (5%) • New onset or worsening • Risk of drug resistance • Nausea (4%) renal impairment with use for preexposure prophylaxis • Abdominal pain (2%) • Lactic acidosis/ severe DISCOVER Population: cis-men and transgender women who have hepatomegaly with sex with men and are at high risk of HIV acquisition • Fatigue (2%) • Risk of post-treatment steatosis acute exacerbation of TRIAL Comparator: Truvada • Headache (2%) hepatitis B

6. Descovy (emtricitabine and tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; December 2019. 6. Descovy (emtricitabine and tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; December 2019. 9. Hare B, Coll P, Ruane P, et al. The phase 3 DISCOVER study: daily F/TAF or F/TDF for HIV preexposure prophylaxis. Presented at: The annual Conference on 7. Descovy. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020. Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. Abstract 104.

Descovy® - Place in Therapy Descovy® - Patient Access

non-inferior to Truvada for HIV prevention Commercial Medicaid Medicare

as low as $0 less impact on serum creatinine and proteinuria preferred covered by per month with medication most plans co-pay card less impact on bone mineral density

6. Descovy (emtricitabine and tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; December 2019. 9. Hare B, Coll P, Ruane P, et al. The phase 3 DISCOVER study: daily F/TAF or F/TDF for HIV preexposure prophylaxis. Presented at: The annual Conference on 5. Preferred Drug List. Utah Department of Health Medicaid. Accessed January 23, 2020. Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. Abstract 104. 10. Welcome to the Gilead Advancing Access® Co-pay Program. Gilead Advancing Access® Medication Co-pay Coupon Card. Accessed January 22, 2020.

Descovy® - Patient Access romosozumab-aqqg

COVERAGE DETAILS Evenity™

• For commercially insured patients who are residents of the US, Puerto Rico, or US Territories • Must be ≥ 18 years to use card for self or a minor • Covers up to $7,200 per year with no monthly limit

10. Welcome to the Gilead Advancing Access® Co-pay Program. Gilead Advancing Access® Medication Co-pay Coupon Card. Accessed January 22, 2020.

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Evenity™ - Overview Evenity™ - Overview

MECHANISM OF ACTION

humanized monoclonal antibody that binds to and inhibits sclerostin, a regulatory 04.09.19 DOSING factor in bone metabolism FDA APPROVAL 210 mg bone formation ONCE MONTHLY postmenopausal osteoporosis for 12 months INDICATION in those at high risk for bone resorption fracture or who failed or are intolerant to other therapy

11. Evenity (romosozumab-aqqg) [prescribing information]. Thousand Oaks, CA: Amgen Inc; April 2019. 11. Evenity (romosozumab-aqqg) [prescribing information]. Thousand Oaks, CA: Amgen Inc; April 2019. 12. Evenity. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020. 12. Evenity. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020.

Evenity™ - Overview Evenity™ - Administration

ADMINISTER INTO ABDOMEN, THIGH, not indicated in patients of reproductive potential OR OUTER AREA OF UPPER ARM

KEEP SYRINGES AT ROOM TEMPERATURE FOR no dose adjustment needed 30 min ≥30 MINUTES PRIOR TO ADMINISTRATION

USE DIFFERENT SITES FOR THE no dose adjustment needed TWO CONSECUTIVE INJECTIONS

Evenity™ - Adverse Effects Evenity™ - Place in Therapy

Population: postmenopausal women with a T-score of COMMON SERIOUS BLACK BOX WARNING FRAME -2.5 to -3.5 at hip or femoral neck • Arthralgia (8-13%) STUDY Comparator: placebo for 12 months followed by • Hypocalcemia • Potential risk of open-label denosumab in both groups • Headache (5-7%) • Osteonecrosis of the jaw myocardial infarction, • Muscle spasms (3-5%) stroke, and Population: postmenopausal women with osteoporosis • Atypical subtrochanteric cardiovascular death ARCH and a fragility fracture • Asthenia (2-3%) and diaphyseal femoral STUDY Comparator: weekly alendronate for 12 months followed • Peripheral edema (2%) fractures by open-label alendronate in both groups • Neck pain (2%) • Insomnia (2%) Population: postmenopausal women with osteoporosis STRUCTURE and history of fracture who were receiving oral • Paresthesia (1-2%) STUDY bisphosphonates ≥ 3 years prior to enrollment Comparator: teriparatide

13. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017;377(15):1417-1427. 14. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532-1543. 11. Evenity (romosozumab-aqqg) [prescribing information]. Thousand Oaks, CA: Amgen Inc; April 2019. 15. Langdahl BL, Libanati C, Crittenden DB, et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis 12. Evenity. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. Accessed January 23, 2020. transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. The Lancet. 2017;390(10102):1585-1594.

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Evenity™ - Place in Therapy Evenity™ - Patient Access

lower risk of fracture compared with alendronate alone Commercial Medicaid Medicare

usually requires as low as $25 lower risk of vertebral fracture compared with placebo non-preferred; PA; 80% of cost per month with PA required covered by Part B co-pay card after deductible is met gains in hip BMD not observed with teriparatide

13. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017;377(15):1417-1427. 14. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532-1543. 15. Langdahl BL, Libanati C, Crittenden DB, et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis 5. Preferred Drug List. Utah Department of Health Medicaid. Accessed January 23, 2020 transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. The Lancet. 2017;390(10102):1585-1594. 16. Paying for EVENITY™. Evenity. https://www.evenity.com/paying-for-evenity. Accessed January 23, 2020.

Evenity™ - Patient Access Other Notable New Drugs

• Fluticasone propionate/salmeterol inhalation powder (AirDuo® Digihaler™): asthma COVERAGE DETAILS • Glucagon nasal powder(Baqsimi™): hypoglycemia • Levamlodipine maleate (Conjupri®): hypertension • Covers up to $8,000 per year • Lemborexant (Dayvigo™): insomnia with no monthly limit • Aclidinium bromide/formoterol fumarate inhalation powder (Duaklir® Pressair®): COPD • Can be applied to deductible, • Glucagon ready‐to‐use injection (Gvoke™): hypoglycemia co-insurance, and/or co-pay • Cellulose and citric acid capsules (Plenity®): weight management ™ • Does not cover any physician- • Lasmiditan tablets (Reyvow ): acute migraine ™ related services associated • Esketamine nasal spray(Spravato ): treatment‐resistant major depressive disorder with administration • Omeprazole magnesium, amoxicillin, rifabutin capsules (Talicia®): H. pylori GI tract infection • Sumatriptan nasal spray (Tosymra™): acute migraine • Ubrogepant tablets (Ubrelvy™): acute migraine

16. Paying for EVENITY™. Evenity. https://www.evenity.com/paying-for-evenity. Accessed January 23, 2020. 17. Center for Drug Evaluation and Research. New Drug Therapy Approvals 2019. U.S. Food and Drug Administration. Accessed January 20, 2020.

Test Questions Test Questions

Which of the following is a Black Box Warning associated with Evenity™? Which of the following statements about Rybelsus® is TRUE?

® A. Risk of thyroid C-cell tumors A. Rybelsus demonstrated superior cardiovascular safety compared to placebo B. Risk of hepatitis B exacerbation B. Rybelsus® demonstrated inferior weight loss compared to liraglutide and C. Risk of osteonecrosis of the jaw empagliflozin ® D. Risk of MI, stroke, and cardiovascular death C. Rybelsus should be stopped 2 months prior to a planned pregnancy D. Rybelsus should not be used in patients with renal insufficiency

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Test Questions Test Questions

Which of the following patients would be eligible to take Descovy® for PReP? How would you transition a patient from subcutaneous semaglutide to oral semaglutide? A. 32-year old cisgender male who has multiple male sexual partners and a CrCl of 24 mL/min A. Begin oral semaglutide 3 mg within 7 days of last subcutaneous injection B. 27-year old cisgender female that engages in vaginal sex with an HIV- positive male partner B. Begin oral semaglutide 3 mg ≥ 8 days after last subcutaneous injection C. 58-year old transgender female with a recent diagnosis of gonorrhea who C. Begin oral semaglutide 7 mg within 7 days of last subcutaneous injection has 2 sexual partners D. Begin oral semaglutide 7 mg ≥ 8 days after last subcutaneous injection D. 14-year old cisgender male weighing 33 kg who infrequently uses condoms

References Questions 1. Rybelsus (semaglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; September 2019. 2. Rybelsus. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. http://micromedex.com/. Accessed January 23, 2020. 3. A quick guide to the PIONEER trials. Medicine Matters diabetes . https://diabetes.medicinematters.com/semaglutide/cardiovascular-outcomes/a-quick-guide-to-the-pioneer- trials/16877792. Published October 2019. Accessed January 27, 2020. 4. Savings & Support: RYBELSUS® (semaglutide) tablets 7 mg or 14 mg. Product R®. https://www.rybelsus.com/savings-and-support.html. Accessed January 23, 2020. 5. Preferred Drug List. Utah Department of Health Medicaid. https://medicaid.utah.gov/pharmacy/preferred-drug-list/. Accessed January 23, 2020. 6. Descovy (emtricitabine and tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; December 2019. 7. Descovy. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. http://micromedex.com/. Accessed January 23, 2020. 8. TAF Component of DESCOVY FOR PrEP™. HCP. https://www.descovyhcp.com/taf-pharmacology#. Accessed January 27, 2020 9. Hare B, Coll P, Ruane P, et al. The phase 3 DISCOVER study: daily F/TAF or F/TDF for HIV preexposure prophylaxis. Presented at: The annual Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. Abstract 104 10. Welcome to the Gilead Advancing Access® Co-pay Program. Gilead Advancing Access® Medication Co-pay Coupon Card. https://www.gileadadvancingaccess.com/copay-coupon- card. Accessed January 22, 2020. 11. Evenity (romosozumab-aqqg) [prescribing information]. Thousand Oaks, CA: Amgen Inc; April 2019. 12. Evenity. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. http://micromedex.com/. Accessed January 23, 2020. [email protected] 13. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017;377(15):1417-1427. doi:10.1056/nejmoa1708322. 14. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532-1543. doi:10.1056/nejmoa1607948. 15. Langdahl BL, Libanati C, Crittenden DB, et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. The Lancet. 2017;390(10102):1585-1594. doi:10.1016/s0140-6736(17)31613-6. 16. Paying for EVENITY™. Evenity. https://www.evenity.com/paying-for-evenity. Accessed January 23, 2020. 17. Center for Drug Evaluation and Research. New Drug Therapy Approvals 2019. U.S. Food and Drug Administration. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular- entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019. Accessed January 20, 2020.