Teva Launches First Generic Versions of HIV-1 Treatments TRUVADA® (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) and ATRIPLA® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) Tablets in the U.S.

Rhea-AI Summary

Teva Pharmaceuticals USA has launched the FDA-approved generic versions of TRUVADA® and ATRIPLA® tablets, marking a significant step in increasing access to HIV treatments. These generics complement Teva's portfolio of over 10 HIV-related medications on the WHO's Essential Medicines list. The new generics provide vital options for the 1.2 million individuals living with HIV-1 in the U.S., as well as addressing the global shortfall of 12.6 million people without access to treatment. The wholesale acquisition cost is set at $48.51 per tablet for Emtricitabine/Tenofovir and $78.86 for the combination tablet.

Positive

• Launch of FDA-approved generic versions of TRUVADA and ATRIPLA expands Teva's HIV treatment portfolio.
• Increases access to affordable HIV therapies for patients in the U.S.
• Strong commitment to public health with over 10 HIV-related medications on WHO's Essential Medicines list.

Negative

• None.

TEL AVIV & PARSIPPANY, N.J.--(BUSINESS WIRE)--Teva Pharmaceuticals USA, Inc., a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), today announced the availability of the first Food and Drug Administration (FDA)-approved generic versions of TRUVADA^®i and ATRIPLA^®i tablets.

“As the global leader in producing and supplying generics, Teva is excited to launch these medications which further our commitment to delivering more treatment options to patients,” said Brendan O’Grady, Executive Vice President, North America Commercial, Teva. “These products, in addition to our more than 10 HIV-related medications already on the World Health Organization’s Essential Medicines list, represent Teva’s continued pursuit of treatments for HIV to improve health outcomes for the HIV community. During the COVID-19 pandemic, access to treatment is more essential than ever for those who are immunocompromised and at risk of developing more severe disease.”

With 1.2 million people currently living with HIV-1 in the U.S., Teva is committed to increasing access to critical HIV therapies.ⁱⁱ Despite significant advances in the treatment and prevention of HIV over the last two decades, there are still 12.6 million people globally who are unable to obtain treatment today.ⁱⁱⁱ With the introduction of these new generic HIV treatment options, Teva strives to further increase access to important therapies.

These newly available generic medicines are indicated for:

• Emtricitabine and Tenofovir Disoproxil Fumarate Tablets:
  • Treatment of HIV-1 infection when used with other anti-HIV-1 medicines in adults and children who weigh at least 37 pounds (at least 17 kilograms)
  • HIV-1 pre-exposure prophylaxis (PrEP) to reduce the risk of getting HIV-1 infection in adults and adolescents who weigh at least 77 pounds (at least 35 kilograms)

• Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate Tablets:
  • Treatment of HIV-1 infection in people who weigh at least 88 pounds (40 kilograms), alone as a complete regimen, or in combination with other anti-HIV-1 medicines

Emtricitabine and Tenofovir Disoproxil Fumarate Tablets and Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate Tablets are both combination treatments available as a single pill with similar safety profiles to their reference products.

Emtricitabine and Tenofovir Disoproxil Fumarate Tablets are expected to be available through retailers and wholesalers at a Wholesale Acquisition Cost (WAC) of $48.51 per tablet. Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate Tablets are expected to be available through retailers and wholesalers at a WAC of $78.86 per tablet. Actual costs to individual patients and providers are anticipated to be lower than WAC because WAC does not account for additional rebates and discounts that may apply. Savings on out-of-pocket costs may vary depending on the patient’s insurance payer and eligibility for participation in the assistance program. More information is available at TevaHIVgenerics.com.

Emtricitabine 200 Mg/Tenofovir Disoproxil Fumarate 300 Mg

IMPORTANT SAFETY INFORMATION

WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B and RISK OF DRUG RESISTANCE WITH USE OF EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE TABLETS FOR HIV-1 PRE­EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED EARLY HIV-1 INFECTION   Severe acute exacerbations of hepatitis B (HBV) have been reported in HBV-infected individuals who have discontinued emtricitabine and tenofovir disoproxil fumarate tablets. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in individuals who are infected with HBV and discontinue emtricitabine and tenofovir disoproxil fumarate tablets. If appropriate, anti-hepatitis B therapy may be warranted.   Emtricitabine and tenofovir disoproxil fumarate tablets used for HIV-1 PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiating and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP if signs or symptoms of acute HIV-1 infection are present unless negative infection status is confirmed.

Contraindications: Emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status.

Severe Acute Exacerbation of Hepatitis B in Individuals with HBV Infection: All individuals should be tested for the presence of chronic hepatitis B virus (HBV) before or when initiating emtricitabine and tenofovir disoproxil fumarate tablets. Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in HBV-infected individuals who have discontinued emtricitabine and tenofovir disoproxil fumarate tablets. Individuals infected with HBV who discontinue emtricitabine and tenofovir disoproxil fumarate tablets should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.

Comprehensive Management to Reduce the Risk of Sexually Transmitted Infections, Including HIV-1, and Development of HIV-1 Resistance When Emtricitabine and Tenofovir Disoproxil Fumarate Tablets Is Used for HIV-1 PrEP: Use emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP to reduce the risk of HIV-1 infection as part of a comprehensive prevention strategy that includes other prevention measures, including adherence to daily administration and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). The time from initiation of emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.

Use emtricitabine and tenofovir disoproxil fumarate tablets to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV-negative. HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only emtricitabine and tenofovir disoproxil fumarate tablets, because emtricitabine and tenofovir disoproxil fumarate tablets alone does not constitute a complete regimen for HIV-1 treatment; therefore, care should be taken to minimize the risk of initiating or continuing emtricitabine and tenofovir disoproxil fumarate tablets before confirming the individual is HIV-1 negative. While using emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP, HIV-1 testing should be repeated at least every 3 months, and upon diagnosis of any other STIs.

Counsel HIV-1uninfected individuals to strictly adhere to the once daily emtricitabine and tenofovir disoproxil fumarate tablets dosing schedule. The effectiveness of emtricitabine and tenofovir disoproxil fumarate tablets in reducing the risk of acquiring HIV-1 is strongly correlated with adherence, as demonstrated by measurable drug levels in clinical trials of emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP. Some individuals, such as adolescents, may benefit from more frequent visits and counseling to support adherence.

New Onset or Worsening Renal Impairment: Emtricitabine and tenofovir are principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of TDF, a component of emtricitabine and tenofovir disoproxil fumarate tablets. Emtricitabine and tenofovir disoproxil fumarate tablets should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on TDF. Some patients required hospitalization and renal replacement therapy. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction.

Immune Reconstitution Syndrome: Immune reconstitution syndrome has been reported in HIV-1 infected patients treated with combination antiretroviral therapy, including emtricitabine and tenofovir disoproxil fumarate tablets.

Bone Loss and Mineralization Defects: In clinical trials in HIV-1 infected adults and in a clinical trial of HIV-1 uninfected individuals, TDF (a component of emtricitabine and tenofovir disoproxil fumarate tablets) was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving TDF. Assessment of BMD should be considered for adult and pediatric patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with TDF use.

Lactic Acidosis/Severe Hepatomegaly with Steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including FTC and TDF, components of emtricitabine and tenofovir disoproxil fumarate tablets, alone or in combination with other antiretrovirals.

Risk of Adverse Reactions Due to Drug Interactions: The concomitant use of emtricitabine and tenofovir disoproxil fumarate tablets and other drugs may result in known or potentially significant drug interactions, some of which may lead to possible clinically significant adverse reactions from greater exposures of concomitant drugs. Consider the potential for drug interactions prior to and during therapy with emtricitabine and tenofovir disoproxil fumarate tablets; review concomitant medications during therapy with emtricitabine and tenofovir disoproxil fumarate tablets; and monitor for adverse reactions associated with the concomitant drugs.

Pregnancy: There is an Antiretroviral Pregnancy Registry that monitors pregnancy outcomes in women exposed to emtricitabine and tenofovir disoproxil fumarate tablets during pregnancy. Data on the use of emtricitabine and tenofovir disoproxil fumarate tablets during pregnancy from observational studies have shown no increased risk of major birth defects. Available data from the APR show no significant difference in the overall risk of major birth defects with first trimester exposure for emtricitabine or tenofovir disoproxil fumarate compared with the background rate for major birth defects in a U.S. reference population.

Lactation: Based on published data, FTC and tenofovir have been shown to be present in human breast milk. Because of the potential for: HIV transmission (in HIV-negative infants); developing viral resistance (in HIV-positive infants); and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are taking emtricitabine and tenofovir disoproxil fumarate tablets for the treatment of HIV-1. In HIV-uninfected women, the developmental and health benefits of breastfeeding and the mother’s clinical need for emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP should be considered along with any potential adverse effects on the breastfed child from emtricitabine and tenofovir disoproxil fumarate tablets and the risk of HIV-1 acquisition due to nonadherence and subsequent mother to child transmission.

Common Adverse Reactions: In clinical trials, the most common adverse reactions (incidence greater than or equal to 10%, all grades) in HIV-1 infected subjects included diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. In HIV-1 uninfected adults in PrEP trials, adverse reactions that were reported by more than 2% of participants and more frequently than by placebo participants were headache, abdominal pain, and decreased weight.

Please see full Prescribing Information, including Boxed Warning.

Efavirenz 600 Mg/Emtricitabine 200 Mg/Tenofovir Disoproxil Fumarate 300 Mg

IMPORTANT SAFETY INFORMATION

WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B

Severe acute exacerbations of hepatitis B virus (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.   Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Contraindications: Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.

Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are contraindicated to be coadministered with voriconazole or elbasvir/grazoprevir.

Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV

All patients should be tested for the presence of chronic HBV before or when initiating antiretroviral therapy. Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued FTC or TDF, two of the components of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Patients who are coinfected with HIV-1 and HBV should be closely monitored, with both clinical and laboratory follow-up for at least several months after stopping treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. If appropriate, initiation of antihepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.

Rash

In controlled clinical trials, 26% of adult subjects treated with 600 mg EFV experienced new-onset skin rash compared with 17% of those treated in control groups. Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first 2 weeks of initiating therapy with EFV and, in most subjects continuing therapy with EFV, rash resolves within 1 month. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. For patients who have had a life-threatening cutaneous reaction (e.g., Stevens-Johnson syndrome), alternative therapy should be considered.

Rash was reported in 32% of pediatric subjects treated with EFV. The median time to onset of rash in pediatric subjects was 28 days. Prophylaxis with appropriate antihistamines before initiating therapy with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets in pediatric patients should be considered.

Hepatotoxicity

Postmarketing cases of hepatitis, including fulminant hepatitis progressing to liver failure requiring transplantation or resulting in death, have been reported in patients treated with EFV, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.

Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are not recommended for patients with moderate or severe hepatic impairment. Careful monitoring is recommended for patients with mild hepatic impairment receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.

Monitoring of liver enzymes before and during treatment is recommended for all patients. Consider discontinuing efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets in patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range.

Discontinue efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets if elevation of serum transaminases is accompanied by clinical signs or symptoms of hepatitis or hepatic decompensation.

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

The concomitant use of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and other drugs may result in potentially significant drug interactions, some of which may lead to:

• Loss of therapeutic effect of concomitant drug or efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and possible development of resistance.
• Possible clinically significant adverse reaction from greater exposures of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets or concomitant drug.

QTc prolongation has been observed with the use of EFV. Consider alternatives to efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes.

Psychiatric Symptoms

Serious psychiatric adverse experiences have been reported in patients treated with EFV, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets including severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions.

Patients with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that the symptoms may be related to the use of EFV, and if so, to determine whether the risks of continued therapy outweigh the benefits.

Nervous System Symptoms

Fifty-three percent of subjects receiving EFV in controlled trials reported central nervous system symptoms (any grade, regardless of causality) compared to 25% of subjects receiving control regimens. These symptoms included dizziness, insomnia, impaired concentration, somnolence, abnormal dreams, and hallucinations. Other reported symptoms were euphoria, confusion, agitation, amnesia, stupor, abnormal thinking, and depersonalization. Patients should be informed that these common symptoms were likely to improve with continued therapy and were not predictive of subsequent onset of the less frequent psychiatric symptoms.

Late-onset neurotoxicity, including ataxia and encephalopathy (impaired consciousness, confusion, psychomotor slowing, psychosis, delirium), may occur months to years after beginning EFV therapy. Patients presenting with signs and symptoms of serious neurologic adverse experiences should be evaluated promptly to assess the possibility that these events may be related to EFV use, and whether discontinuation of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets is warranted.

Patients receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets should be alerted to the potential for additive central nervous system effects when efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are used concomitantly with alcohol or psychoactive drugs.

Patients who experience central nervous system symptoms such as dizziness, impaired concentration, and/or drowsiness should avoid potentially hazardous tasks such as driving or operating machinery.

New Onset or Worsening Renal Impairment

Emtricitabine and tenofovir are principally eliminated by the kidney; however, EFV is not. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of TDF, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.

Prior to initiation and during use of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are not recommended in patients with moderate or severe renal impairment (estimated creatinine clearance below 50 mL/min).

Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on TDF. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction.

Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in patients at risk of renal dysfunction.

Discontinue efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.

Embryo-Fetal Toxicity

Efavirenz may cause fetal harm when administered during the first trimester of pregnancy. Advise adults and adolescents of childbearing potential who are receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets to avoid pregnancy while receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and for 12 weeks after discontinuation.

Bone Loss and Mineralization Defects

Bone Mineral Density

In clinical trials in HIV-1 infected adults, TDF (a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets) was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving TDF.

Under normal circumstances, BMD increases rapidly in pediatric patients. In HIV-1 infected subjects aged 2 years to less than 18 years, bone effects were similar to those observed in adult subjects and suggest increased bone turnover. Total body BMD gain was less in the TDF-treated HIV-1 infected pediatric subjects as compared to the control groups. Similar trends were observed in chronic hepatitis-B infected adolescent subjects aged 12 years to less than 18 years.

Mineralization Defects

Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with TDF use. Arthralgias and muscle pain or weakness have also been reported in cases of proximal renal tubulopathy. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving TDF-containing products.

Convulsions

Convulsions have been observed in adult and pediatric patients receiving EFV, generally in the presence of known medical history of seizures. Caution must be taken in any patient with a history of seizures.

Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including TDF and FTC, components of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, alone or in combination with other antiretrovirals. Treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

Fat Redistribution

Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance," has been observed in patients receiving antiretroviral therapy, including EFV.

Common Adverse Reactions: In clinical trials, the most common adverse reactions (incidence greater than or equal to 10%, any severity) in HIV-1 infected subjects included diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.

Please see full Prescribing Information, including Boxed Warning.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, regarding the launch of our generic versions of Truvada® (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) and Atripla® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) tablets, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to:

• The commercial success of our generics products portfolio, including our generic versions of products for prevention and treatment of HIV-1 in the U.S.;
• our ability to successfully compete in the marketplace, including: that we are substantially dependent on our generic products; consolidation of our customer base and commercial alliances among our customers; the increase in the number of competitors targeting generic opportunities and seeking U.S. market exclusivity for generic versions of significant products; competition for our specialty products, especially COPAXONE®, our leading medicine, which faces competition from existing and potential additional generic versions, competing glatiramer acetate products and orally-administered alternatives; the uncertainty of commercial success of AJOVY® or AUSTEDO®; competition from companies with greater resources and capabilities; delays in launches of new products and our ability to achieve expected results from investments in our product pipeline; ability to develop and commercialize biopharmaceutical products; efforts of pharmaceutical companies to limit the use of generics, including through legislation and regulations and the effectiveness of our patents and other measures to protect our intellectual property rights;
• our substantial indebtedness, which may limit our ability to incur additional indebtedness, engage in additional transactions or make new investments, may result in a further downgrade of our credit ratings; and our inability to raise debt or borrow funds in amounts or on terms that are favorable to us;
• our business and operations in general, including: uncertainty regarding the magnitude, duration, and geographic reach of the COVID-19 pandemic and its impact on our business, financial condition, operations, cash flows, and liquidity and on the economy in general; interruptions in our supply chain, including due to potential effects of the COVID-19 pandemic on our operations and business in geographic locations impacted by the pandemic and on the business operations of our customers and suppliers; adequacy of and our ability to successfully execute and maintain the activities and efforts related to the measures we have taken or may take in response to the COVID-19 pandemic and associated costs therewith; effectiveness of our restructuring plan announced in December 2017; challenges associated with conducting business globally, including adverse effects of the COVID-19 pandemic, political or economic instability, major hostilities or terrorism; our ability to attract, hire and retain highly skilled personnel; our ability to develop and commercialize additional pharmaceutical products; compliance with anti-corruption sanctions and trade control laws; manufacturing or quality control problems; disruptions of information technology systems; breaches of our data security; variations in intellectual property laws; significant sales to a limited number of customers; our ability to successfully bid for suitable acquisition targets or licensing opportunities, or to consummate and integrate acquisitions; our prospects and opportunities for growth if we sell assets and potential difficulties related to the operation of our new global enterprise resource planning (ERP) system;
• compliance, regulatory and litigation matters, including: our ability to successfully defend against the DOJ criminal charges of a Sherman Act violations; increased legal and regulatory action in connection with public concern over the abuse of opioid medications in the U.S. and our ability to reach a final resolution of the remaining opioid-related litigation; costs and delays resulting from the extensive governmental regulation to which we are subject or delays in governmental processing time including due to modified government operations due to the COVID-19 pandemic and effects on product and patent approvals; the effects of reforms in healthcare regulation and reductions in pharmaceutical pricing, reimbursement and coverage; governmental investigations into S&M practices; potential liability for patent infringement; product liability claims; increased government scrutiny of our patent settlement agreements; failure to comply with complex Medicare and Medicaid reporting and payment obligations; and environmental risks;
• other financial and economic risks, including: our exposure to currency fluctuations and restrictions as well as credit risks; potential impairments of our intangible assets; potential significant increases in tax liabilities; and the effect on our overall effective tax rate of the termination or expiration of governmental programs or tax benefits, or of a change in our business;

and other factors discussed in our Quarterly Reports on Form 10-Q for the first and second quarters of 2020 and our Annual Report on Form 10-K for the year ended December 31, 2019, including in the sections captioned "Risk Factors” and “Forward Looking Statements.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.

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ⁱ TRUVADA and ATRIPLA are registered trademarks of Gilead Sciences, Inc.
ⁱⁱ Minority HIV/AIDS Fund. Fast Facts. HIV.gov. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics#:~:text=An%20estimated%201.2%20million%20people,which%20this%20information%20is%20available. Accessed September 2020.
ⁱⁱⁱ HIV.gov. The Global HIV/AIDS Epidemic. Available: https://www.hiv.gov/federal-response/pepfar-global-aids/global-hiv-aids-overview#:~:text=HIV%20Treatment%20Access%E2%80%94As%20of,as%20a%20public%20health%20threat. Accessed August 2020.