P
`
`age
`
`1
`
`0
`
`f 1 1
`
`Astraleneca Exhibit 2135
`Mylan v. Astraleneca
`IPR2015-01340
`
`AstraZeneca Exhibit 2135
`Mylan v. AstraZeneca
`IPR2015-01340
`
`Page 1 of 11
`
`

`
`kombiglyzexn
`(saxa Iiptin and metformin HCI
`endedrelease) tablets
`
`Important Safety Information for KOMBIGLYZE XR
`
`KOMBIGLYZE XR can cause serious side
`
`effects. including:
`
`Lactic Acidosis: Metformin hydrochloride, one of the
`medicines in KOMBIGLYZE XR, can cause a rare, but
`
`serious, side effect called lactic acidosis (a build-up of
`lactic acid in the blood) that can cause death. Lactic
`acidosis is a medical emergency and must be treated in
`a hospital. Stop taking KOMBIGLYZE XR and call your
`doctor right away if you get any of the following
`symptoms of lactic acidosis: feel very weak and tired,
`unusual (not normal) muscle pain, trouble breathing,
`unusual sleepiness or sleep longer than usual,
`unexplained stomach or intestinal problems with
`nausea and vomiting or diarrhea, feel cold (especially in
`your arms and legs), dizzy or lightheaded, or have a slow
`or irregular heartbeat.
`
`You have a higher chance of getting lactic acidosis if
`you have kidney or liver problems, have congestive
`heart failure that requires treatment with medicines.
`drink a lot of alcohol (very often or short-term "binge"
`drinking), get dehydrated (lose a large amount of body
`fluids), have certain x—ray tests with injectable dyes or
`contrast agents, have surgery, have a heart attack,
`severe infection, or stroke, or are 80 years of age or
`older and have not had your kidney function tested.
`
`Please see Important Safety Information on page 9.
`Click here for Medication Guide and click here for full
`Prescribing Information for KOMBIGLYZE XR (5/500,
`5/1000, 2.5/1 000 mg tablets), including Boxed WARNING
`about possible lactic acidosis.
`
`Page 2 of 11
`
`
`
`Managing type 2 diabetes can be challenging.
`Especially if you're taking metformin and finding that
`it isn't doing enough to get your A1C numbers to goal.
`For some, combining metformin with another kind
`of type 2 medicine may work better. This combination
`pill could be the kickstart you need.
`
`What is KOMBIGLYZE XR?
`
`KOMBIGLYZE XR is a prescription medicine that
`contains saxagliptin and metformin hydrochloride.
`KOMBIGLYZE XR is used with diet and exercise to help
`control high blood sugar (hyperglycemia) in adults with
`type 2 diabetes. Your doctor will decide if treatment
`with both saxagliptin and metformin is right for you.
`
`KOMBIGLYZE XR should not be used to treat people
`with type 1 diabetes or diabetic ketoacidosis
`(increased ketones in the blood or urine).
`
`FitF&IMe. Eifitfililigfifrliif
`just medicine, there's the F'rt2Me diet and
`lifestyle support program custom-fit to you.
`Learn more about Fit2Me on page 8.
`
`Page 2 of 11
`
`

`
`kombiglyzexn
`‘S”‘2%'é?.ll2o%?élel$§él?5Llé?s”°'
`
`PROVEN TO LOWER
`A1C LEVELS
`
`for patients whose blood sugarwas
`not controlled with metformin alone
`
`One very important goal in managing type 2 diabetes
`is lowering yourA1C level to a number agreed upon
`by you and your healthcare provider.
`
`The combination of saxagliptin and metformin
`hydrochloride, the two medicines that make up
`KOMBIGLYZE XR, has been tested in multiple clinical
`studies in thousands of adult patients with type 2
`diabetes. In all of these studies, KOMBIGLYZE XR,
`in addition to diet and exercise, has been shown to
`lower A1C levels.
`
`These results are the average responses from the
`total population in these studies. Your personal
`results may vary.
`
`Your healthcare providerwill determine if
`KOMBIGLYZE XR could give you the kickstart you
`need to reach yourA1C goals.
`
`Talk to your healthcare provider to see if
`
`KOMBIGLYZE XR is right for you.
`
`Please see Important Safety Information on page 9.
`Click here for Medication Guide and click here for full
`Prescribing Information for KOMBIGLYZE XR (5/500,
`5/1 000, 2.5/1000 mg tablets), including Boxed WARNING
`about possible lactic acidosis.
`
`Page 3 of 11
`
`Who should not take KOMBIGLYZE XR?
`
`Do not take KOMBIGLYZE XR if you have kidney
`problems, have a condition called metabolic acidosis or
`diabetic ketoacidosis (increased ketones in the blood
`or urine), or are allergic to metformin hydrochloride,
`saxagliptin, or any of the ingredients in KOMBIGLYZE
`XR. Serious allergic reactions can occur with
`KOMBIGLYZE XR and may include swelling of the face,
`lips or throat, difficulty swallowing or breathing,
`swelling of the skin, hives, rash, itching, flaking, or
`peeling. If you have these symptoms, stop taking
`KOMBIGLYZE XR and contact your doctor right away.
`
`Page 3 of 11
`
`

`
`kombiglyzexn
`(saxagliptin and metformin HCI
`extended-release) tablets
`
`Talk to your healthcare provider to see if
`
`KOMBIGLYZE XR is right for you.
`
`Please see Important Safety lnformation on page 9.
`Click here for Medication Guide and click here for full
`Prescribing information for KOMBIGLYZE XR (5/500,
`5/1000, 2.5/1 000 mg tablets), including Boxed WARNING
`about possible lactic acidosis.
`
`Page 4 of 11
`
`24-WEEK CLINICAL STUDY
`
`A 24-week clinical study involved 1,306 adult type 2
`diabetes patients whose blood sugar was not
`controlled enough by diet and exercise. Of these
`patients, 643 were given saxagliptin plus metformin IR,
`335 were given saxagliptin plus placebo and 328 were
`given a placebo plus metformin IR.
`
`The patients started the study with an A1C of 9.4%
`to 9.6%, on average.
`
`After 24 weeks, results showed
`significantA1C reduction.
`
`Patients who took saxagliptin plus
`metformin IR:
`
`0 lowered their A1C by 2.5% on average
`0 60% of patients reached an A1C goal
`of less than 7%‘
`*Your results may vary
`
`What is the most important information you
`should know about KOMBIGLYZE XR?
`
`Serious side effects can happen to people taking
`KOMBIGLYZE XR, including inflammation of the
`pancreas (pancreatitis)which may be severe and lead
`to death. Before taking KOMBIGLYZE XR, tell your
`doctor if you ever had pancreatitis, gallstones, history
`of alcoholism, or high triglyceride levels. Stop taking
`KOMBIGLYZE XR and contact your doctor right away if
`you have pain in your stomach area (abdomen) that is
`severe and will not go away. The pain may be felt going
`from your abdomen through to your back. The pain may
`happen with or without vomiting. These may be
`symptoms of pancreatitis,
`
`Page 4 of 11
`
`

`
`kombiglyzexn
`(saxa Iiptin and metformin HCI
`ended—re|ease) tablets
`
`KOMBIGLYZE XR IS
`BELIEVED TO WORK IN
`4 DIFFERENT WAYS
`
`to help control blood sugar
`
`Not all medicines for type 2 diabetes work the
`same way. The graphic below demonstrates how
`KOMBIGLYZE XR is believed to work in four
`
`different ways to help control blood sugar.
`
`
`insulin when you eat
`
`works to decrease the amount
`of sugar absorbed by the gut
`
`works to reduce the amount
`of sugar made by the liver
`
`helps the body respond
`better to its own insulin
`
`helps your body make more
`
`INSUUN
`
`What is the most important information you
`should know about KOMBIGLYZE XR?
`
`Heart Failure. Before taking KOMBIGLYZE XR tell your
`doctor if you have ever had heart failure or problems with
`your kidneys. Contact your doctor right away if you have
`any of the following symptoms of heart failure: increasing
`shortness of breath or trouble breathing, especially when
`you lie down; an unusually fast increase in weight; swelling
`in the feet, ankles or legs
`Page 5 of 11
`
`Talk to your healthcare provider to see if
`
`KOMBIGLYZE XR is right for you.
`
`Please see Important Safety lnformation on page 9.
`Click here for Medication Guide and click here for full
`Prescribing lnformation for KOMBlGLYZE XR (5/500,
`5/1 000, 2.5/1 000 mg tablets), including Boxed WARNING
`about possible lactic acidosis.
`
`Page 5 of 11
`
`

`
`kombiglyzexn
`lsaxagliptin and metformin HCI
`extended-release) tablets
`
`ONCE-A-DAY KOMBIGLYZE XR
`must be taken as prescribed
`
`KOMBIGLYZE XR is generally taken once a day with
`your evening meal to help lessen an upset stomach
`side effect. Swallow the tablets whole—don't crush,
`
`cut, or chew them, and don't change your close
`without speaking with your healthcare provider.
`
`When taking KXR, be sure to contact your doctor right
`away ifyou have a fever, trauma, infection or surgery
`as this may change your medication needs.
`
`Stay on your prescribed diet and exercise program
`while taking KOMBIGLYZE XR.
`
`Your healthcare provider should request
`blood tests to check how well your
`kidneys are working before and during
`your treatment with KOMBIGLYZE XR.
`
`Important Safety Information for KOMBIGLYZE XR
`
`Ifyou take KOMBIGLYZE XR with another medicine
`that can cause low blood sugar (hypoglycemia), such as
`sulfonylureas or insulin, you have a higher risk of having
`low blood sugar. Symptoms of low blood sugar include
`shaking, sweating, rapid heartbeat, change in vision,
`hunger, headache, and change in mood. Follow your
`doctor's instructions for treating low blood sugar.
`
`Some people who take medicines called DPP-4
`inhibitors, one of the medicines in KOMBIGLYZE XR,
`
`may developjoint pain that can be severe. Call your
`doctor if you have severe joint pain.
`
`Page 6 of 11
`
`Talk to your healthcare provider to see if
`
`KOMBIGLYZE XR is right for you.
`
`Please see Important Safety Information on page 9.
`Click here for Medication Guide and click here for full
`Prescribing Information for KOMBIGLYZE XR (5/500,
`5/1000, 2.5/1 000 mg tablets), including Boxed WARNING
`about possible lactic acidosis.
`
`Page 6 of 11
`
`

`
`komhiglyzexn
`(saxa Iiptin and metformin HCI
`ended-release) tablets
`
`
`
`YOU MAY BE ABLE TO GET
`KOMBIGLYZE XR FOR
`AS LOW AS $0 A MONTH’
`
`for as long as your doctor prescribes it
`
`CO-PAYs
`
`AS LITTLE AS
`
`:
`
`,- 2:
`
`ulusunqnu
`
`Ems-.,.,.-..
`sm.oo4ca2
`PCN8 CM
`GRP: ECOOOOODOD
`ID: XXXXXXXXXXX
`-Q-aqua
`‘:3’:-nbllnligplatfiuqix
`
`E.-':.:.-:‘..-.:.-:::...-...,..
`
`go to: kombiglyzesavings.com
`TO GET YOUR CARD TODAY!
`
`‘Eligible commercially insured patients can get KOMBIGLYZE XR for as
`low as $0 per month for as long as your doctor prescribes an available
`close. Subject to eligibility. Restrictions apply. Not available for
`government-insured patients.
`
`Please see Important Safety Information on page 9.
`Click here for Medication Guide and click here for full
`Prescribing Information for KOMBIGLYZE XR (5/500,
`5/1 000, 2.5/1 000 mg tablets including Boxed WARNING
`about possible lactic acidosis.
`
`Page 7 of 11
`
`ELIGIBILITY AND TERMS OF USE
`
`ELIGIBILITY: You may be elig ble for this offer if you are insured by
`commercial insurance and your insurance does not cover the full cost
`of your prescription, or you are not insured and are responsible for
`the cost of your prescriptions. Patients who are enrolled in a state
`or federally funded prescription insurance program are not eligible
`for this offer. This includes patients enrolled in Medicare Part D,
`Medicaid, Medigap, Veterais Affairs (VA). Department of Defense
`(DOD) programs or Tricare. and patients who are Medicare eligible
`and enrolled in an employer-sponsored group waiver health plan or
`govemment-subsidized prescription drug benefit program for retirees.
`If you are enrolled in a state or federally funded prescription insurance
`program, you may not use this savings card even if you elect to be
`processed as an uninsured (cash-paying) patient. This offer is not
`insurance. is restricted to residents of the United States and Puerto
`Rico, and to patients over 18 years of go.
`
`TERMS OF USE: Eligible commercially insured patients with a valid
`prescription for KOMBIGLYZE XR who present this savings card at
`participating pharmacies will pay $0 per 30-day supply subject
`to a maximum savings of $150 per 3041ay supply. If you pay cash
`for your prescription, Astraleneca will pay up to the first $150,
`and you will be responsible for any remaining balance, for each monthly
`prescription. Other restrictions may apply. Patient is responsible for
`applicable taxes, if any. Non-transferable, limited to one per person,
`cannot be combined with any other offer. Void where proh bited by law,
`taxed or restricted. Patients, pharmacists, and prescribers cannot seek
`reimbursement from health insurance or any third party for any part
`of the benefit received by the patient through this offer. Astraleneca
`reserves the right to rescind, revoke, or amend this offer, eligibility and
`terms of use at any time without notice. This offer is not conditioned
`on any past, present or future purchase. including refills. Offer must be
`presented along with a valid prescription at the time of purchase. If you
`have my questions regarding this offer, please call 1-855-907-3197.
`
`BY USING THIS CARD. YOU AND YOUR PHARMACIST UNDERSTAND
`AND AGREE TO COMPLY WITH THESE ELIGIBILITY REQUIREMENTS
`AND TERMS OF USE.
`
`Page 7 of 11
`
`

`
`kombiglyzexn
`(saxa liptin and metformin HCI
`endetlrelease) tablets
`
`SURROUNDING YOU
`WITH SUPPORT
`
`We're here to help
`
`If you and your healthcare provider decide that
`KOMBIGLYZE XR is the right treatment for you, you'll
`have a place to turn to for questions about your medicine
`and any cost issues you may have. Our goal is to make
`managingyour type 2 diabetes management plan easier.
`Remember, in addition to your healthcare provider,
`our team is here foryou every step along the way.
`
`KOMBIGLYZE XR Care Partners‘
`
`Get connected to a variety of support
`services, tips, and information with the help
`of KOMBIGLYZE XR Care Partners.
`
`KOMBIGLYZE XR Prescription
`Coverage Counselors’
`
`We have Prescription Coverage Counselors
`with whom you can talk on the phone about
`your KOMBIGLYZE XR coverage and benefit
`verification. They can help you determine your
`co-pay amount and what information you'll
`need to process your benefit verification.
`
`‘KOMBIGLYZE XR Care Partners cannot provide medical advice
`and can only provide information about AstraZeneca medications.
`Decisions regardingyour health and treatment of your condition
`should be made with your own healthcare provider.
`
`*Prescription Coverage Counselors do not file claims or appeals
`on behalf of patients or healthcare professionals. Coverage or
`co-pay amounts may change prior to the time of actual
`prescription fill.
`
`Visit kombiglyzexrcom or call
`
`888-985-9738 toll-free.
`
`Page 8 of 11
`
`FitFflMe.
`
`Discover a type 2 diabetes diet and lifestyle
`support program that's custom-fit to you
`
`Fit2Me was designed to help you manage your
`diabetes, your way. It creates a customized plan for
`you to follow, based on choices that work best for you.
`This free program is centered around 4 key areas:
`
`1
`
`*1
`
`My Food
`
`Food: pick the ingredients,
`cuisines, and recipes you like
`
`Activity: choose your favorite
`activities and your activity level
`
`Treatment Information: get
`information to help you and
`your doctor make decisions
`about your treatment
`
`Support: select a digital coach
`with a personality type that
`motivates you the most
`
`My Plan Team
`
`My Treatment
`
`Consult with your healthcare provider before making
`any changes to your diabetes management plan and
`before starting any diet or exercise program.
`
`Create a plan that's fit to you
`at Fit2Me.com.
`
`Please see important Safety information on page 9.
`Click here for Medication Guide and click here for full
`Prescribing information for KOMBIGLYZE XR (5fl500,
`5/1 000, 2.5/1000 mg tablets), including Boxed WARNING
`about possible lactic acidosis.
`
`Page 8 of 11
`
`

`
`kombiglyzexn
`(saxa Iiptin and metformin HCI
`ended»release) tablets
`
`IMPORTANT SAFETY INFORMATION FOR
`
`KOMBIGLYZE XR
`
`KOMBIGLYZE XR can cause serious side
`
`effects. including:
`
`Lactic Acidosis: Metformin hydrochloride, one of the
`medicines in KOMBIGLYZE XR. can cause a rare. but
`serious, side effect called lactic acidosis (a build-up of
`lactic acid in the blood) that can cause death. Lactic
`acidosis is a medical emergency and must be treated in a
`hospital. Stop taking KOMBIGLYZE XR and call your
`doctor right away if you get any of the following
`symptoms of lactic acidosis: feel very weak and tired,
`unusual (not normal) muscle pain, trouble breathing.
`unusual sleepiness or sleep longer than usual.
`unexplained stomach or intestinal problems with
`nausea and vomiting or diarrhea, feel cold (especially
`in your arms and legs), dizzy or lightheaded. or have a
`slow or irregular heartbeat.
`
`You have a higher chance of getting lactic acidosis if you
`have kidney or liver problems. have congestive heart
`failure that requires treatment with medicines, drink a
`lot of alcohol (very often or short-term "binge"
`drinking), get dehydrated (lose a large amount of body
`fluids), have certain x-ray tests with injectable dyes or
`contrast agents. have surgery. have a heart attack.
`severe infection, or stroke, or are 80 years of age or
`older and have not had your kidney function tested.
`
`Do not take KOMBIGLYZE XR if you:
`
`- Have kidney problems, have a condition called metabolic
`acidosis or diabetic ketoacidosis (increased ketones in
`the blood or urine), or are allergic to metformin
`hydrochloride, saxagliptin, or any of the ingredients in
`KOMBIGLYZE XR. Serious allergic reactions can occur
`with KOMBIGLYZE XR and may include swelling of the
`face, lips or throat, difficulty swallowing or breathing
`swelling of the skin, hives, rash, itching, flaking, or
`peeling. If you have these symptoms, stop taking
`KOMBIGLYZE XR and contact your doctor right away
`
`Serious side effects can happen in people who
`take KOMBIGLYZE XR:
`
`- Inflammation of the pancreas (pancreatitis) which
`may be severe and lead to death. Before taking
`KOMBIGLYZE XR. tell your doctor if you ever had
`pancreatitis, gallstones, history of alcoholism, or high
`Page 9 of 11
`
`triglyceride levels. Stop taking KOMBIGLYZE XR and
`contact your doctor right away if you have pain in your
`stomach area (abdomen) that is severe and will not go
`away. The pain may be felt going from your abdomen
`through to your back. The pain may happen with orwithout
`vomiting. These may be symptoms of pancreatitis
`
`- Heart Failure. Before taking KOMBIGLYZE XR tell your
`doctor if you have ever had heart failure or problems
`with your kidneys. Contact your doctor right away if you
`have any of the following symptoms of heart failure:
`increasing shortness of breath or trouble breathing,
`especially when you lie down; an unusually fast increase
`in weight; swelling in the feet, ankles or legs
`- Your doctor should do blood tests to check how well
`
`your kidneys are working before and during your
`treatment with KOMBIGLYZE XR
`
`- If you take KOMBIGLYZE XR with another medicine that
`can cause low blood sugar (hypoglycemia), such as
`sulfonylureas or insulin, you have a higher risk of having
`low blood sugar. Symptoms of low blood sugar include,
`shaking, sweating, rapid heartbeat, change in vision,
`hunger, headache and change in mood. Follow your
`doctofs instructions for treating low blood sugar
`
`- Some people who take medicines called DPP-4
`inhibitors, one of the medicines in KOMBIGLYZE XR.
`may develop joint pain that can be severe. Call your
`doctor if you have severejoint pain
`The most common side effects of KOMBIGLYZE XR
`
`include upper respiratory tract infection, stuffy or
`runny nose and sore throat, urinary tract infection,
`headache, diarrhea, and nausea and vomiting.
`
`Tell your healthcare provider:
`
`- if you will be starting or stopping certain other types
`of medicines, such as antibiotics, or medicines that
`treat fungus or HIV/AIDS, as your doctor may need to
`change your dose of KOMBIGLYZE XR
`
`- if you are pregnant, breast-feeding, or plan to become
`pregnant or breast-feed
`Swallow KOMBIGLYZE XR whole; do not crush, cut,
`or chew.
`
`You are encouraged to report negative side effects
`of prescription drugs to the FDA
`Visit www.FDAgov/medwatch or call 1 -800-FDA-I 088.
`
`Click IQ for Medication Guide and click IQ for full
`Prescribing Information for KOMBIGLYZE XR (5/500,
`5/1000, 2.5/1000 mg tablets), including Boxed
`WARNING about possible lactic acidosis.
`
`Page 9 of 11
`
`

`
`kombiglyzexn
`(saxa Iiptin and metlormin HCI
`e ended-release) tablets
`
`-9-
`
`
`
`1. What is my A1C now?
`
`2.What is my A1C goal?
`
`3. Can KOMBIGLYZE XR help lower my A1C?
`
`4. What important safety information should I know?
`
`Before your next appointment:
`
`1. Make a list of any changes to the medicines
`you're taking.
`
`2. Bring notes or questions about your treatment options.
`
`3. Ask about the right type 2 diabetes medicine for you.
`
`Important Safety Information for KOMBIGLYZE XR
`
`The most common side effects of KOMBIGLYZE XR
`include upper respiratory tract infection, stuffy or
`runny nose and sore throat, urinary tract infection,
`
`headache, diarrhea, and nausea and vomiting.
`
`_
`DO YOU need 3 klckstart t0 h€lP l0WeT YOUF Alc?
`Be sure to ask your doctor.
`
`Page 10 of 11
`
`10
`
`Page 10 of 11
`
`

`
`kombiglyzexn
`(saxagliptin and metformin HCI
`extended-release) tablets
`
`Ask your healthcare provider
`about KOMBIGLYZE XR and
`
`visit kombiglyzexncom
`to learn how you can save.
`
`11
`
`KOMBIGLYZE XR is a registered trademark of the Astrazeneca
`group of companies.
`©2016 Mtraleneca. All rights reserved.
`3“fi°33g%“fT‘§%‘fi
`
`AstraZeneca§
`
`Page 11 of 11