Are biosimilars the next frontier in drug development?

A conversation on reducing costs

Biological products are the fastest growing class of therapeutic products in the U.S.¹ Biosimilars are biological products that are highly similar to a reference product in terms of structure and function and have no clinically meaningful differences in safety, purity, or potency from their reference product.² They are treatment options that work similarly, but are potentially less expensive, than the originator biologic.^3,4,5,6

In this Q&A, Tom Rainey, Senior Vice President, Specialty Sales & Marketing for Teva Pharmaceuticals, discusses Teva’s focus on biosimilars and an industry need to find balance between rewarding innovation and simplifying the pathway to bringing biosimilars to market.⁵

Why did Teva decide to focus on biosimilars?

Teva’s mission is to be a global leader in generics and biopharmaceuticals. Today, we are focused on delivering roughly 3,000 medicines, including generics, biosimilars, and specialty medicines to nearly 200 million people every day.^7,8 Teva believes that unlocking the hidden value in biosimilars for patients and payers is an important new frontier in drug development.

A focus on biosimilars is a natural progression for Teva following our role in building the generic medicine(s) industry over the past 40 years. Focusing on biosimilars allows us to combine our strength in generics with our knowledge of complex medicine(s). As one of the largest fully integrated manufacturing and delivery networks in the pharmaceutical industry, we are committed to continuing to make innovative medicines more accessible.⁹

How is Teva’s approach to biosimilars different from other companies?

Teva is committed to building a leadership position in biosimilars and growing our portfolio of biosimilar medicines as part of our global focus on biopharmaceuticals – drawing on our expertise in branded medicines and generics.

Our strategic partnerships with Celltrion Healthcare and Alvotech have allowed us to bring together highly complementary capabilities to secure a leading position in the U.S. biosimilar market⁷, and help offer patients and health care providers treatments that are potentially less expensive.^3,4,5,6

What barriers or challenges have you faced in the development and launch of biosimilars?

Biologics are innovative treatment options often for debilitating and life-threatening diseases that can have high development costs.^10,11 In the case of oncology, multiple treatments are sometimes needed. Biologics also require a complex research, development, and manufacturing process.¹¹

The Biosimilars pathway can help reduce these complexities; however, we believe there’s still work to be done to help simplify the pathway and increase the transparency of bringing a biosimilar medication to market. Our goal in turn, is to help reduce costs for patients.^4,5,6 Companies should be rewarded for the lengthy regulatory and intellectual property processes required for their innovative biologics, but at the same time adjustments should be made to the timeline to allow for quicker entry into the market. We’ve experienced the barriers the timeline imposes, and even after they launch, providers may, in our experience, continue to use the reference products even though they may have higher wholesale acquisition costs (WAC) and average sales price (ASP). We believe some of the reasons may be reluctance to substitute with a biosimilar, cost of adding products in their systems, and reimbursement challenges.⁹ Drawing on our expertise in generics, we’d like to continue working closely with providers and payers to overcome these barriers and help reduce costs for their patients. We believe there are lessons from our experience with generics that can be applied to the biosimilar space.

Innovation and access to much-needed treatment is more important now than ever. If we look at the accomplishment of having a COVID-19 vaccine available to Americans less than one year into a global pandemic, we see what is possible when we collaborate to accomplish health goals and bring much needed medications to market. How much more in cost savings could we offer patients if we worked together to address the barriers of bringing a biosimilar medication to market? More research is needed.

What is most rewarding about the work you do in biosimilars? What are you most looking forward to?

We’re looking forward to advancing our mission and growing our portfolio of biosimilar medicines. Through our partnership with Alvotech, we are expanding patient access for biosimilar medicines in the U.S. The initial pipeline through this collaboration includes five biosimilar candidates, that address multiple therapeutic areas, which means we now have 12 biosimilars in our pipeline.¹³

Most rewarding is the ability to potentially help patients that are suffering from debilitating or life-threatening diseases, and offering treatment options in a category of medications that may help lower their burden of cost.^4,5,6 The biosimilars industry has the potential to help 1.2 million patients by 2025¹⁴ and reduce costs by $54 billion from 2017-2026⁴, and that is certainly something to be optimistic about.

In 2019, Teva launched TRUXIMA^® (rituximab-abbs) injection in the U.S. as the first biosimilar to the reference product Rituxan^® (rituximab).^15,16 TRUXIMA then launched in the U.S. as the first biosimilar to the reference product for the treatment of rheumatoid arthritis.¹⁷ (SCROLL DOWN TO CONTINUE ARTICLE)

APPROVED USE

TRUXIMA is a prescription medicine used to treat adults with:

• Non-Hodgkin’s Lymphoma (NHL): alone or with other chemotherapy medicines
• Chronic Lymphocytic Leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide
• Rheumatoid Arthritis (RA): with another prescription medicine called methotrexate, to reduce the signs and symptoms of moderate to severe active RA, after treatment with at least one other medicine called a tumor necrosis factor (TNF) antagonist has been used and did not work well
• Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA): with glucocorticoids, to treat GPA and MPA

• TRUXIMA is not indicated for treatment of children.

IMPORTANT SAFETY INFORMATION
TRUXIMA can cause serious side effects that can lead to death, including:

• Infusion-related reactions. Infusion-related reactions are very common side effects of TRUXIMA treatment. Serious infusion-related reactions can happen during your infusion or within 24 hours after your infusion of TRUXIMA. Your healthcare provider should give you medicines before your infusion of TRUXIMA to decrease your chance of having a severe infusion-related reaction

Please see additional Important Safety Information below and full Prescribing Information including Medication Guide.

(CONTINUED)

TRUXIMA is one of the most successful launches in the U.S. biosimilars market, capturing over 20% of market share in less than one year from launch.¹⁸

In 2020, HERZUMA^® (trastuzumab-pkrb) for Injection, a biosimilar to Herceptin^®19, became available with the same indications as the reference product listed below.²⁰ (SCROLL DOWN TO CONTINUE ARTICLE)

APPROVED USE

Patients are selected for therapy with HERZUMA based on an FDA-approved test.

Adjuvant Breast Cancer

HERZUMA is a prescription medicine used for the treatment of early-stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2+) and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high-risk feature. HERZUMA can be used in several different ways:

• As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel. This treatment course is known as “AC → TH”
• With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as “TCH”
• Alone after treatment with multiple other therapies, including an anthracycline (doxorubicin)-based therapy (a type of chemotherapy)

Patients are selected for therapy with HERZUMA based on an FDA-approved test.

Metastatic Breast Cancer
HERZUMA has 2 approved uses in metastatic breast cancer:

• HERZUMA in combination with the chemotherapy drug paclitaxel is approved for the first line treatment of Human Epidermal growth factor Receptor 2-positive (HER2+) metastatic breast cancer
• HERZUMA alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease

Metastatic Gastric Cancer
HERZUMA is approved, in combination with chemotherapy (cisplatin and either capecitabine or 5-fluorouracil), for the treatment of HER2-positive metastatic cancer of the stomach or gastroesophageal junction (where the esophagus meets the stomach) in patients who have not received prior treatment for their metastatic disease.

IMPORTANT SAFETY INFORMATION

HERZUMA can cause serious side effects, including:
HEART PROBLEMS: Trastuzumab products can cause heart problems—such as congestive heart failure or reduced heart function—with or without symptoms. The risk for and seriousness of these heart problems were highest in people who received both a trastuzumab product and a certain type of chemotherapy (anthracycline). In a study of adjuvant (early) breast cancer, one patient died of significantly weakened heart muscle. Your healthcare provider will check for signs of heart problems before, during, and after treatment with HERZUMA.

Please see additional Important Safety Information below and full Prescribing Information including BOXED WARNING.

(CONTINUED)

The launch of HERZUMA continued Teva’s goal to potentially lowering healthcare costs and improve accessibility for patients. ^5,6,11,12

This is only the beginning of our biosimilars work, and we currently have a robust pipeline in development.

TRUXIMA

IMPORTANT SAFETY INFORMATION (CONTINUED)

Tell your healthcare provider or get medical help right away if you get any of these symptoms during or after an infusion of TRUXIMA:

• • hives (red itchy welts) or rash
  • shortness of breath, difficulty breathing, or wheezing
  • itching
  • weakness
  • swelling of your lips, tongue, throat, or face
  • dizziness or feel faint
  • sudden cough
  • palpitations (feel like your heart is racing or fluttering)
  • chest pain

• Severe skin and mouth reactions. Tell your healthcare provider or get medical help right away if you get any of these symptoms at any time during your treatment with TRUXIMA:
  • painful sores or ulcers on your skin, lips, or in your mouth
  • blisters
  • peeling skin
  • rash
  • pustules

• Hepatitis B virus (HBV) reactivation. Before you receive your TRUXIMA treatment, your healthcare provider will do blood tests to check for HBV infection. If you have had hepatitis B or are a carrier of hepatitis B virus, receiving TRUXIMA could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems including liver failure, and death. You should not receive TRUXIMA if you have active hepatitis B liver disease. Your healthcare provider will monitor you for hepatitis B infection during and for several months after you stop receiving TRUXIMA.
  Tell your healthcare provider right away if you get worsening tiredness, or yellowing of your skin or white part of your eyes, during treatment with TRUXIMA
• Progressive Multifocal Leukoencephalopathy (PML). PML is a rare, serious brain infection caused by a virus that can happen in people who receive TRUXIMA. People with weakened immune systems can get PML. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML

Tell your healthcare provider right away if you have any new or worsening symptoms or if anyone close to you notices these symptoms:

• confusion
• decreased strength or weakness on one side of your body
• dizziness or loss of balance
• vision problems
• difficulty walking or talking

Before you receive TRUXIMA, tell your healthcare provider about all of your medical conditions, including if you:

• have had a severe reaction to TRUXIMA or a rituximab product
• have a history of heart problems, irregular heart beat, or chest pain
• have lung or kidney problems
• have an infection or weakened immune system
• have or have had any severe infections including:
  • Hepatitis B virus (HBV)
  • Hepatitis C virus (HCV)
  • Cytomegalovirus (CMV)
  • Herpes simplex virus (HSV)
  • Parvovirus B19
  • Varicella zoster virus (chickenpox or shingles)
  • West Nile virus

• have had a recent vaccination or are scheduled to receive vaccinations. You should not receive certain vaccines before or during treatment with TRUXIMA
• are pregnant or plan to become pregnant. Talk to your healthcare provider about the risks to your unborn baby if you receive TRUXIMA during pregnancy
  Females who are able to become pregnant:
  • Your healthcare provider should do a pregnancy test to see if you are pregnant before starting TRUXIMA
  • You should use effective birth control (contraception) during treatment with TRUXIMA and for 12 months after your last dose of Talk to your healthcare provider about effective birth control
  • Tell your healthcare provider right away if you become pregnant or think that you are pregnant during treatment with TRUXIMA
• are breastfeeding or plan to TRUXIMA may pass into your breast milk. Do not breastfeed during treatment and for 6 months after your last dose of TRUXIMA

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your doctor if you take or have taken:

• a TNF inhibitor medicine
• a Disease Modifying Anti-Rheumatic Drug (DMARD)

If you are not sure if your medicine is one listed above, ask your healthcare provider.
TRUXIMA can cause serious side effects, including:

• Tumor Lysis Syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause you to have:
  • kidney failure and the need for dialysis treatment
  • abnormal heart rhythm

TLS can happen within 12 to 24 hours after an infusion of TRUXIMA. Your healthcare provider may do blood tests to check you for TLS. Your healthcare provider may give you medicine to help prevent TLS.
Tell your healthcare provider right away if you have any of the following signs or symptoms of TLS:

• • nausea
  • vomiting
  • diarrhea
  • lack of energy

• Serious infections. Serious infections can happen during and after treatment with TRUXIMA, and can lead to death. TRUXIMA can increase your risk of getting infections and can lower the ability of your immune system to fight infections. Types of serious infections that can happen with TRUXIMA include bacterial, fungal, and viral infections. After receiving TRUXIMA, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months). Some of these people with low antibody levels developed infections. People with serious infections should not receive TRUXIMA. Tell your healthcare provider right away if you have any symptoms of infection:
  • fever
  • cold symptoms, such as runny nose or sore throat that do not go away
  • flu symptoms, such as cough, tiredness, and body aches
  • earache or headache
  • pain during urination
  • cold sores in the mouth or throat
  • cuts, scrapes, or incisions that are red, warm, swollen, or painful

• Heart problems. TRUXIMA may cause chest pain, irregular heartbeats, and heart attack. Your healthcare provider may monitor your heart during and after treatment with TRUXIMA if you have symptoms of heart problems or have a history of heart problems. Tell your healthcare provider right away if you have chest pain or irregular heartbeats during treatment with TRUXIMA
• Kidney problems, especially if you are receiving TRUXIMA for NHL. TRUXIMA can cause severe kidney problems that lead to death. Your healthcare provider should do blood tests to check how well your kidneys are working
• Stomach and serious bowel problems that can sometimes lead to death. Bowel problems, including blockage or tears in the bowel, can happen if you receive TRUXIMA with chemotherapy medicines. Tell your healthcare provider right away if you have any severe stomach-area (abdomen) pain or repeated vomiting during treatment with TRUXIMA

Your healthcare provider will stop treatment with TRUXIMA if you have severe, serious, or life-threatening side effects.

The most common side effects of TRUXIMA include:

• • infusion-related reactions
  • infections (may include fever, chills)
  • body aches
  • tiredness
  • nausea

The most common side effects of TRUXIMA in adult patients with GPA or MPA include:

• • low white and red blood cells
  • swelling
  • diarrhea
  • muscle spasms

Other side effects with TRUXIMA include:

• • aching joints during or within hours of receiving an infusion
  • more frequent upper respiratory tract infection

These are not all of the possible side effects with TRUXIMA.

Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Teva at 1-888-483-8279.

Please see the TRUXIMA full Prescribing Information, including the Medication Guide.

HERZUMA

IMPORTANT SAFETY INFORMATION (CONTINUED)

HERZUMA can cause serious side effects, including:

• INFUSION REACTIONS: Infusion reactions, sometimes serious or fatal, have occurred. Symptoms may include: fever, chills, feeling sick to your stomach (nausea), throwing up (vomiting), pain (in some cases at tumor site), headache, dizziness, and shortness of breath. These symptoms usually happen within 24 hours after receiving HERZUMA
• SEVERE LUNG PROBLEMS: Trastuzumab product use can result in serious and fatal lung problems. Symptoms may include: severe shortness of breath, fluid in or around the lungs, weakening of the valve between the heart and lungs, not enough oxygen in the body, swelling of the lungs, and scarring of the lungs. Your healthcare provider may check for signs of severe lung problems
• HARM TO UNBORN BABIES OR BIRTH DEFECTS: Trastuzumab products may result in birth defects or the death of an unborn baby. Contraception should be used while receiving HERZUMA and for 7 months after your last dose of HERZUMA. If you are or become pregnant while receiving HERZUMA or within 7 months after your last dose of HERZUMA, you should immediately contact your doctor. Patients should contact their healthcare professional with a known or suspected pregnancy
• LOW WHITE BLOOD CELL COUNTS: Low white blood cell counts (which may be life-threatening) were seen more often in patients receiving trastuzumab plus chemotherapy than in patients receiving chemotherapy alone. Your healthcare provider may check for signs of low white blood cell counts

Your healthcare provider will stop treatment with HERZUMA if you have severe, serious, or life-threatening side effects.

The most common side effects for patients receiving HERZUMA for breast cancer include: headache, diarrhea, feeling sick to your stomach (nausea), chills, fever, infection, weakened heart muscle, unable to sleep, cough, and rash.

The most common side effects for patients receiving HERZUMA for metastatic gastric cancer include: low white blood cell counts, diarrhea, feeling tired, low red blood cell counts, swelling of the mouth lining, weight loss, upper respiratory infections, fever, low platelet counts, swelling of the mucous membranes, swelling of the nose and throat, and change in taste.

These are not all of the possible side effects with HERZUMA.

Please see full Prescribing Information, including BOXED WARNINGS.

Talk to your doctor about any side effects you may experience.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.

For more information, visit TRUXIMA.com and HERZUMA.com.

¹ Industry Information and Guidance. U.S. Food and Drug Administration. 2018. Accessed from: https://www.fda.gov/drugs/biosimilars/industry-information-and-guidance#guidance
² What is a Biosimilar? U.S. Food and Drug Administration. Accessed from: https://www.fda.gov/media/108905/download
³ Biopharma at Teva. Teva Pharmaceuticals. Accessed from: https://www.tevausa.com/our-products/biopharmaceuticals/biopharma-at-teva/
⁴ Mulcahy, Andrew W., Jakub P. Hlavka, and Spencer R. Case. Biosimilar Cost Savings in the United States: Initial Experience and Future Potential. Santa Monica, CA:  RAND Corporation, 2017. https://www.rand.org/pubs/perspectives/PE264.html
⁵ US Food and Drug Administration. Biosimilars. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved
/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/default.htm  Accessed June 23, 2022.
⁶ Data on file. Redbook Herceptin-Herzuma WAC pricing/ASP Pricing files/RST Coding ASP summary Q2 2021.
⁷ Data on file. Teva Biosimilars Talking Points.
⁸ Data on file. Teva Patients Behind the Numbers. April 2019.
⁹ Data on file. Teva 2020 Environmental, Social and Governance Progress Report.
¹⁰ Biosimilars 101. Biosimilars Council. Accessed from: https://biosimilarscouncil.org/biosimilars-101/
¹¹ Wouters OJ, McKee M, Luyten J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA. 2020;323(9):844–853. doi:10.1001/jama.2020.1166.
¹² Biosimilars: What we can learn from early adopters. Cardinal Health. March 2021. Access from https://www.cardinalhealth.com/content/dam/corp/web/documents/whitepaper/cardinal-health-biosimilars-adoption-in-oncology.pdf
¹³ Teva Specialty Product Pipeline by Development Stage – April 2021. Accessed from: https://www.tevapharm.com/globalassets/tevapharm-vision-files/teva-specialty-and-biosim-pipeline-april-2021_final.pdf
¹⁴ Biosimilars in the United States: Providing More Patients Greater Access to Lifesaving Medicines. The Biosimilars Council. 2017. Accessed from: http://biosimilarscouncil.org/wp-content/uploads/2019/03/Biosimilars-Council-Patient-Access-Study.pdf
¹⁵ Rituxan^® (rituximab) prescribing information. A registered trademark of Biogen and Genentech. December 2021. Available at https://www.gene.com/download/pdf/rituxan_prescribing.pdf
¹⁶ TRUXIMA^® (rituximab-abbs) Prescribing Information. Incheon, Republic of Korea: Celltrion, Inc.
¹⁷ US Food and Drug Administration. sBLA approval letter. December 2019. Accessed from: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2019/761088Orig1s005,%20s006ltr.pdf.
¹⁸ Data on file. TRUXIMA^®/HERZUMA^® Management Dashboard. September 2020.
¹⁹ Herceptin^® (trastuzumab) prescribing information. A registered trademark of Genentech. February 2021. Available at https://www.gene.com/download/pdf/herceptin_prescribing.pdf
²⁰ HERZUMA^® (trastuzumab-pkrb) Prescribing Information. Incheon, Republic of Korea: Celltrion, Inc.

RIX-40595
July 2022