"Merck remains resolute in its commitment to help address the unmet needs of people living with HIV and continue to do our part in the global efforts to help end the HIV pandemic, which includes the ongoing development of islatravir," said Dr. Joan Butterton, vice president, infectious diseases, Global Clinical Development, Merck Research Laboratories. "All clinical studies provide important learnings to help us in the fight against HIV, and we are grateful to the patients and investigators for their contributions."

In light of the findings from the MK-8507-013 study, Merck conducted a review of trends in total lymphocyte and CD4+ T-cell counts in company-sponsored clinical trials of ISL across all indications and dosing regimens. A dose-dependent decrease in lymphocyte counts was observed in an ongoing Phase 2 trial (MK-8591-016), which is evaluating monthly ISL (60 mg and 120 mg) for PrEP in participants at low-risk of HIV-1 infection. In this population of HIV-1 uninfected participants, the mean decreases were in the normal range and there was no increase in clinical adverse events (AEs) related to infection. In addition, a small, treatment related mean decrease in CD4+ T-cell counts was observed through Week 48 in two Phase 3 trials, ILLUMINATE SWITCH A and ILLUMINATE SWITCH B (MK-8591A-017 and MK-8591A-018), which are evaluating doravirine 100 mg in combination with ISL 0.75 mg daily (DOR/ISL) in HIV-1 virologically suppressed participants. There was no increased incidence of AEs related to infections in participants receiving DOR/ISL relative to comparators through Week 48. Investigators for these trials have been informed and the trials are continuing. Full results from ILLUMINATE SWITCH A and ILLUMINATE SWITCH B will be presented at an upcoming medical meeting.

Merck has an expansive HIV clinical development program evaluating islatravir across a variety of dosing regimens, for both the treatment of HIV-1 in combination with other antiretroviral agents and for the prevention of HIV-1 as a monotherapy. Merck recently announced positive topline results from the ILLUMINATE SWITCH A and ILLUMINATE SWITCH B Phase 3 clinical trials. As previously reported, at 48 weeks, both trials met their primary efficacy endpoint of percentage of participants with HIV-1 RNA levels ≥50 copies/mL, demonstrating that antiviral efficacy was comparable between DOR/ISL and different antiretroviral therapy regimens (ILLUMINATE SWITCH A) and between DOR/ISL and bictegravir/emtricitabine/tenofovir (ILLUMINATE SWITCH B).

The IMAGINE-DR clinical trial was a Phase 2, randomized, controlled, double-blind, dose-ranging study, designed to evaluate a switch to MK-8507 and ISL in combination as a once-weekly oral treatment in adults with HIV-1 who have been virologically suppressed for greater than or equal to six months on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once-daily. The study had been fully enrolled with 161 participants and was ongoing.

PIFELTRO ™ (doravirine, 100 mg) is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine.

DELSTRIGO™ (doravirine 100 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg) is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of DELSTRIGO. DELSTRIGO contains a boxed warning regarding post-treatment acute exacerbations of hepatitis B (HBV) infection. See Selected Safety Information below.

All patients with HIV-1 should be tested for the presence of HBV before initiating ARV therapy. Severe acute exacerbations of HBV have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing lamivudine or tenofovir disoproxil fumarate (TDF), which are components of DELSTRIGO. Patients coinfected with HIV-1 and HBV who discontinue DELSTRIGO should be monitored with both clinical and laboratory follow-up for at least several months after stopping DELSTRIGO. If appropriate, initiation of anti-HBV therapy may be warranted.

PIFELTRO and DELSTRIGO are contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John's wort (Hypericum perforatum)), as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of DELSTRIGO and PIFELTRO.

Prior to or when initiating DELSTRIGO, and during treatment, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue DELSTRIGO in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Discontinue DELSTRIGO if estimated creatinine clearance declines below 50 mL/min.

In DRIVE-AHEAD, neuropsychiatric adverse events were reported in the three pre-specified categories of sleep disorders and disturbances, dizziness, and altered sensorium. Twelve percent of adult subjects in the DELSTRIGO group and 26% in the EFV/FTC/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DELSTRIGO group and 37% in the EFV/FTC/TDF group reported dizziness; and 4% in the DELSTRIGO group and 8% in the EFV/FTC/TDF group reported altered sensorium.

Islatravir (MK-8591) is Merck's investigational nucleoside reverse transcriptase translocation inhibitor under evaluation in more than 10 clinical trials. For treatment, islatravir is being evaluated in combination with other antiretrovirals, including the ILLUMINATE clinical trials program for a once-daily regimen. In the IMPOWER clinical trials, islatravir is also being studied for pre-exposure prophylaxis (PrEP) of HIV-1 infection as a single agent across a variety of formulations, including an oral once-monthly regimen.

For more than 35 years, Merck has been committed to scientific research and discovery (R&D) in HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV, with the goal of reducing the growing burden of infection worldwide. We remain committed to working hand-in-hand with our partners in the global HIV community to address the complex challenges that impede progress toward ending the epidemic.

For over 130 years, Merck, known as MSD outside the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world's most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

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The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's 2020 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (www.sec.gov).

Please see Prescribing Information for PIFELTRO (doravirine) at: https://www.merck.com/product/usa/pi_circulars/p/pifeltro/pifeltro_pi.pdf; and Patient Information for PIFELTRO (doravirine) at: https://www.merck.com/product/usa/pi_circulars/p/pifeltro/pifeltro_ppi.pdf

Please see Prescribing Information for DELSTRIGO (doravirine/3TC/TDF) at: https://www.merck.com/product/usa/pi_circulars/d/delstrigo/delstrigo_pi.pdf and Patient Information for DELSTRIGO (doravirine/3TC/TDF) at: https://www.merck.com/product/usa/pi_circulars/d/delstrigo/delstrigo_ppi.pdf