Gilead Statement on U.S. Government Complaint Regarding HIV PrEP and PEP Patents

November 7, 2019 – Gilead is aware of the government complaint alleging infringement of patents granted to the U.S. Department of Health and Human Services (HHS) for methods of HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). We strongly believe that the patents granted to HHS since 2015 for PrEP and PEP are not valid and reject any notion of willful infringement. HHS improperly filed for patents without alerting Gilead, despite its obligation to do so, and we have openly explained the defects in the patents since becoming aware of them.

Gilead has acted above board and in good faith to come to a resolution with HHS on the issue of the validity and ownership of the PEP and PrEP patents. Gilead took the first step to resolve this legal dispute by requesting an inter partes review (IPR) of the validity of the HHS patent claims. In doing so, Gilead has both respected and invoked the patent system, engaging the U.S. Patent Trial and Appeal Board — the expert agency set up by Congress to determine if patents may have been improperly granted. We are surprised that the government has requested that a district court judge and jury look at the same issues of patent validity that the Patent Office will be deciding. We will be asking the district court to stay the litigation until the Patent Office has an opportunity to undertake the review that we already have requested.

As we have presented both to HHS and to the Patent Office, there is compelling evidence demonstrating that the HHS patents are invalid. Published materials clearly show that, well before HHS claims to have invented the concepts of PrEP and PEP in 2006, others had conceived of using an antiretroviral therapy, including Truvada® (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg tablets), for both forms of prophylaxis. For example, guidelines published in 2004 recommended administering combination antiretrovirals — including Truvada — to certain categories of “high risk” individuals before an HIV exposure, while the Centers for Disease Control and Prevention’s (CDC) own 2005 guidelines recommended Truvada for prophylaxis immediately after exposure. HHS did not disclose this “prior art” in its initial patent applications, despite its obligation to do so.

The fact remains that Gilead invented Truvada and funded the clinical trials that led to its 2004 FDA approval for use in combination with other antiretroviral agents to treat HIV. The company has spent an estimated $1.1 billion on R&D related to Truvada — to develop the two individual drugs that make up Truvada, invent the combination product that is Truvada, invent its use for HIV treatment and support the clinical trials that led to the approval of Truvada for PrEP®. Similarly, Gilead invented and shouldered the cost of developing Descovy® (emtricitabine 200 mg and tenofovir alafenamide 25 mg tablets). Any claim to the contrary is false.

Despite this patent dispute, Gilead will continue to work collaboratively with federal agencies, including HHS and CDC, on efforts to end the HIV epidemic in the United States. We remain committed to supporting the government’s efforts to substantially increase the number of people at risk for HIV who have access to PrEP through our historic donation and through our own ongoing efforts to address the social and structural barriers to care.

U.S. Indication for Truvada for PrEP

Truvada for PrEP (pre-exposure prophylaxis) is indicated to reduce the risk of sexually acquired HIV-1 in adults and adolescents (≥35 kg) who are at risk for HIV, when used in combination with safer sex practices. HIV-negative status must be confirmed immediately prior to initiation

• If clinical symptoms of acute HIV-1 infection are present and recent exposures (<1 month) are suspected, delay initiation for at least 1 month until HIV-negative status is reconfirmed. Alternatively, confirm HIV-negative status with a test cleared by the FDA to aid in the diagnosis of acute HIV-1 infection

U.S. Important Safety Information for Truvada for PrEP

BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF TRUVADA FOR PrEP IN UNDIAGNOSED EARLY HIV-1 INFECTION and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

• Truvada for PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiation and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of Truvada for PrEP following undetected acute HIV-1 infection. Do not initiate if signs or symptoms of acute HIV-1 infection are present unless HIV-negative status is confirmed.
• Severe acute exacerbations of hepatitis B have been reported in HBV-infected patients who discontinued Truvada. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients with HBV after discontinuing Truvada. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Contraindications

• Truvada for PrEP is contraindicated in individuals with unknown or positive HIV status.

Warnings and precautions: Comprehensive risk reduction strategies

• Reduce HIV-1 risk: Truvada for PrEP is not always effective in preventing HIV-1. Use only as part of a comprehensive prevention strategy that includes safer sex practices, regular testing for HIV-1 and other STIs, and counseling on reducing sexual risk behaviors.
• Reduce potential for drug resistance: Truvada for PrEP should only be used in individuals confirmed to be HIV-negative immediately prior to initiation, at least every 3 months while taking Truvada, and upon an STI diagnosis. HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only Truvada. Truvada alone is not a complete regimen for treating HIV-1.
  • HIV antibody tests may not detect acute HIV infection. If recent exposures are suspected or symptoms of acute HIV infection are present (e.g., fever, fatigue, myalgia, skin rash), delay initiating (≥1 month) or discontinue use and confirm HIV-negative status with a test approved by the FDA for the diagnosis of acute HIV infection
  • If a screening test indicates possible HIV-1 infection, convert the HIV-1 PrEP regimen to an HIV treatment regimen until HIV-negative status is confirmed.
• Counsel on adherence: Counsel individuals to strictly adhere to their dosing schedule, as efficacy is strongly correlated with adherence. Some individuals, such as adolescents, may benefit from more frequent visits and counseling.

Warnings and precautions

• New onset or worsening renal impairment: Cases of acute renal impairment and Fanconi syndrome have been reported with the use of tenofovir disoproxil fumarate (TDF). Truvada is not recommended in individuals with estimated creatinine clearance (CrCl) <60 mL/min. Avoid concurrent or recent use with a nephrotoxic agent. Acute renal failure has been reported after initiation of high dose or multiple NSAIDs in patients at risk for renal dysfunction; consider alternatives to NSAIDs in these patients. Monitor renal function in all patients – See Dosage and Administration section.
• Bone effects: Decreases in bone mineral density (BMD) and mineralization defects, including osteomalacia associated with proximal renal tubulopathy, have been reported with the use of TDF. Consider monitoring BMD in patients with a history of pathologic fracture or risk factors for bone loss.
• Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including Truvada. Discontinue use if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
• Drug interactions: See Drug Interactions section. Consider the potential for drug interactions prior to and during use of Truvada and monitor for adverse reactions.

Adverse reactions

• Common adverse reactions (>2% and more frequently than placebo) of Truvada for PrEP in clinical trials were headache, abdominal pain, and weight loss.

Drug interactions

• Prescribing information: Consult the full Prescribing Information for Truvada for more information, warnings, and potentially significant drug interactions, including clinical comments.
• Hepatitis C antivirals: Coadministration with ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, or sofosbuvir/velpatasvir/voxilaprevir increases TDF exposure; monitor for adverse reactions.
• Drugs affecting renal function: Coadministration of Truvada with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine and/or tenofovir. 

Pregnancy and lactation

• Pregnancy: An Antiretroviral Pregnancy Registry (APR) has been established. Available data from observational studies and the APR show no increase in the rate of major birth defects for Truvada compared with a US reference population. Consider HIV prevention methods, including Truvada for PrEP in women due to the potential increased risk of HIV-1 infection during pregnancy and mother to child transmission during acute HIV-1 infection.
• Lactation: Emtricitabine and tenofovir have been detected in human milk. Evaluate the benefits and risks of Truvada for PrEP in breastfeeding women, including the risk of HIV-1 acquisition due to nonadherence, and subsequent mother to child transmission. Health benefits of breastfeeding should be considered along with potential adverse effects of Truvada on the child, which are unknown.

Dosage and administration

• Dosage: One tablet once daily with or without food.
• HIV screening: Test for HIV-1 infection prior to initiating and at least every 3 months during treatment.
• HBV screening: Test for HBV infection prior to or when initiating treatment.
• Renal impairment and monitoring: Not recommended in individuals with CrCl <60 mL/min. In all patients, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein on a clinically appropriate schedule. In patients with chronic kidney disease, also assess serum phosphorus.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors. It is not possible to determine the outcome of the patent infringement lawsuit filed by HHS related to HIV PrEP and PEP patents. There is also the possibility that the U.S. Patent Trial and Appeal Board (PTAB) may deny institution of Gilead’s petitions for inter partes review of the validity of the HHS patent claims. Further, even if PTAB institutes Gilead’s petitions for inter partes review, PTAB may not rule in Gilead’s favor. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full Prescribing Information for Truvada and Descovy, including BOXED WARNING, is available at www.gilead.com.

GILEAD, TRUVADA, TRUVADA FOR PrEP and DESCOVY are trademarks of Gilead Sciences Inc., or its related companies.