Today is a milestone moment in the decades-long fight to end the HIV epidemic. The FDA has approved our twice-yearly HIV prevention medicine, Yeztugo (lenacapavir), an innovation that's been called a “breakthrough” by public health leaders and made headlines around the world when the clinical trial results were announced last year.

 

Yeztugo is the first and only pre-exposure prophylaxis medication that only has to be given twice a year. This makes a significant difference because prevention only works when people can realistically incorporate it into their lives. The twice-yearly dosing, along with the remarkable clinical data, make Yeztugo a medicine that could transform HIV prevention.

 

The work on this groundbreaking innovation started nearly 20 years ago when Gilead scientists began to explore whether targeting the capsid of the virus could lead to something new and better for HIV. It took the screening of more than 4,000 molecules to find the breakthrough. Our teams saw the potential for Yeztugo to help end the HIV epidemic, and it is thanks to their perseverance that this goal is now within reach.

 

I have spent my entire career in the biopharma industry, and I have never experienced the profound sense of possibility that comes with this medicine. Thirty years ago, HIV was still essentially a death sentence and, while we have made tremendous progress since then, the fight against HIV is far from finished.

 

HIV infects around 1.3 million people a year and contrary to common perceptions, it affects every demographic. In many parts of the world, incidence is rising fastest among women and adolescent girls. The most recent available data show 1.2 million Americans are living with HIV. Sadly 100 people die every week in the United States from HIV-related illness and more than 700 are newly diagnosed.

 

We now have an opportunity to bend the arc of the epidemic with Yeztugo. Achieving that goal will, of course, take more than innovation. We need to ensure this breakthrough reaches the people and communities who need it most and that has been just as much of a focus for us as the science. With input from multiple stakeholders in the field of HIV, we have been working to ensure unprecedented levels of access since the clinical trials began.

 

Before the first regulatory filing last year, we licensed lenacapavir to generics manufacturers so they can provide generic versions to 120 primarily low- and lower-middle-income countries, once approved. For the period before these generics become available, we are working with global aid organizations to provide branded Yeztugo at no profit to Gilead for at least 2 million people over three years. Our strategy also includes tailored approaches for middle-income countries, including tiered pricing and public-private partnerships.

 

In the U.S. we are helping to ensure eligible people who are without insurance can still access this potentially life-saving medicine through our patient assistance programs. For people with commercial insurance, we have taken additional steps to help with their copay. We are committed to supporting access for all those who can benefit from Yeztugo.

 

These steps are all critical, and we also need government policies and funding that support HIV services, including testing, linkage to care and surveillance. Gilead Sciences, along with many others, is in dialogue with policymakers to underscore why continued support is so essential to progress.

 

It has taken a tremendous amount of work to get us to this point. Beyond the discovery and development of Yeztugo by Gilead Sciences, this achievement also belongs to many others. We owe enormous gratitude to the global community accountability groups, HIV community organizations, the advocates, the public health leaders, the people who took part in our clinical trials, and many more who all share our commitment to ending the HIV epidemic. The scientists who have worked in HIV through the years also share in this, because every advance in HIV prevention and treatment has helped to set the stage for this next leap forward in innovation.

 

What matters most to all these groups, and to all of us at Gilead Sciences is making sure we turn this innovation into impact. If we meet this moment with the attention it deserves, we can create a future where people can live without the fear of HIV. It is my great hope that we look back at this milestone as THE inflection point in the effort to end the HIV epidemic.

Please see below for the U.S. Indication and Important Safety Information for Yeztugo for HIV prevention, including Boxed Warning.

 

U.S. Indication for Yeztugo

Yeztugo (lenacapavir) injection, 463.5 mg/1.5 mL, is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents (>35kg) who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating Yeztugo.

U.S. Important Safety Information for Yeztugo

BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF YEZTUGO IN UNDIAGNOSED HIV-1 INFECTION

Individuals must be tested for HIV-1 infection prior to initiating Yeztugo, and with each subsequent injection of Yeztugo, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been identified with use of Yeztugo by individuals with undiagnosed HIV-1 infection. Do not initiate Yeztugo unless negative infection status is confirmed. Individuals who acquire HIV-1 while receiving Yeztugo must transition to a complete HIV-1 treatment regimen.

Contraindications

Yeztugo is contraindicated in individuals with unknown or positive HIV-1 status.

Warnings and precautions

Comprehensive risk management:

Use Yeztugo to reduce the risk of HIV-1 acquisition as part of a comprehensive prevention strategy including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs).

HIV-1 acquisition risk includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or present STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network. Counsel individuals on the use of other prevention methods to help reduce their risk.

Use Yeztugo only in individuals confirmed to be HIV-1 negative. Evaluate for current or recent signs or symptoms consistent with HIV-1 infection. Confirm HIV-1 negative status prior to initiating, prior to each subsequent injection, and as clinically appropriate.

Potential risk of resistance:

 

There is a potential risk of developing resistance to Yeztugo if an individual acquires HIV-1 before or when receiving Yeztugo, or following discontinuation. HIV- 1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection taking only Yeztugo, because Yeztugo alone is not a complete regimen for HIV-1 treatment.

To minimize this risk, it is essential to test before each injection and additionally as clinically appropriate. Individuals confirmed to have HIV-1 must immediately begin a complete HIV-1 treatment regimen.

Alternative forms of PrEP should be considered after discontinuation of Yeztugo for those who are at continuing risk of HIV-1 acquisition and should be initiated within 28 weeks of the last Yeztugo injection.

Long-acting properties and potential associated risks:

 

Residual concentrations of Yeztugo may remain in systemic circulation for up to 12 months or longer after the last injection.

Select individuals who agree to the required injection dosing schedule because nonadherence or missed doses could lead to HIV-1 acquisition and development of resistance.

 

Serious injection site reactions: Improper administration (intradermal injection) has been associated with serious injection site reactions, including necrosis and ulcer. Only administer Yeztugo subcutaneously.

 

Adverse reactions

Most common adverse reactions (≥5%) in Yeztugo clinical trials were injection site reactions, headache, and nausea.

Drug interactions

Strong or moderate CYP3A inducers may significantly decrease Yeztugo concentrations. Dosage modifications are recommended when initiating these inducers.

It is not recommended to use Yeztugo with combined P-gp, UGT1A1, and strong CYP3A inhibitors.

Coadministration of Yeztugo with sensitive substrates of CYP3A or P-gp may increase their concentrations and result in the increased risk of their adverse events. Yeztugo may increase the exposure of drugs primarily metabolized by CYP3A initiated within 9 months after the last injection of Yeztugo.

 

Dosage and administration

HIV screening: Test for HIV-1 infection prior to initiating, prior to each subsequent injection, and as clinically appropriate using an approved or cleared test for the diagnosis of acute or primary HIV-1 infection.

Dosage: Initiation dosing (injections and tablets) followed by once-every-6-months continuation injection dosing. Tablets may be taken with or without food.

Initiation: Day 1: 927 mg by subcutaneous injection (2 x 1.5-mL injections) and 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally.

Continuation: 927 mg by subcutaneous injection every 6 months (26 weeks) from date of last injection ±2 weeks.

Anticipated delayed injections: If scheduled 6-month injection is anticipated to be delayed by more than 2 weeks, Yeztugo tablets may be taken on an interim basis (for up to 6 months) until injections resume. Dosage is 300 mg orally (1 x 300-mg tablet) once every 7 days. Resume continuation injections within 7 days of the last oral dose.

Missed injections: If more than 28 weeks have elapsed since the last injection and Yeztugo tablets have not been taken, restart with initiation dosing if clinically appropriate.

Dosage modifications of Yeztugo are recommended when initiating with strong or moderate CYP3A inducers. Consult the full Prescribing Information for recommendations.

For more information on Yeztugo, please see the full Prescribing Information including Boxed Warning, available here.