Merck to Present New Data from its HIV Portfolio at the 17th European AIDS Conference
November 6, 2019 6:45 am ET
Presentations Will Feature Analyses from the Company’s Approved and Investigational HIV Medicines
Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced today that new data from its broad HIV portfolio will be presented at the 17th European AIDS Conference (EACS 2019) taking place Nov. 6 – 9, 2019 in Basel, Switzerland. Merck will share a post-hoc analysis from Phase 2 and 3 trials evaluating the effect of doravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), on body weight and body mass index in treatment naïve adults with HIV-1; a post-hoc analysis defining baseline characteristic differences between female and male participants in Phase 2 and 3 doravirine trials; and a sub-analysis of Phase 2 efficacy and safety data for islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI).
“We look forward to the presentations of important new information at the EACS 2019 congress, including data readouts for doravirine and our investigational compound islatravir across key demographic and clinical subgroups,” said Dr. George Hanna, vice president and therapeutic area head of infectious diseases, Global Clinical Development, Merck Research Laboratories. “Pursuing meaningful HIV science remains a key area of focus for Merck, and we continue to gain important insights from our clinical trials evaluating Merck’s approved and investigational anti-HIV agents.”
Select abstracts in the EACS 2019 program include:
- Effect of Doravirine on Body Weight and Body Mass Index in Treatment Naïve Adults with HIV-1. Oral Presentation. Thursday, November 7, 10:00 AM – 12:00 PM. Presentation: PS3/2. Orkin C, et al.
- Islatravir Efficacy and Safety for Selected Demographic and Baseline Subgroups from a Phase 2 trial in Treatment Naïve Adults with HIV-1 infection. Late breaker e-poster. Presentation: PE3/21. Molina JM, et al.
- Differences in Baseline Characteristics Between Men and Women Study Participants: Data from the Doravirine Phase 2/3 Clinical Trials. E-poster. Presentation: PE3/9. Walmsley S, et al.
- Incidence of CKD With TDF and Non-TDF Containing Antiretroviral Regimens by Baseline D:A:D[i] CKD Risk In People Living With HIV (PLWH). Oral Presentation. Thursday, November 7, 2:00 PM – 4:00 PM. Presentation: PS4/2. Hsu R, et al.
- Changes in LDL After Switch from TDF to TAF in the U.S. E-poster. Presentation: PE2/44. Mallon P, et al.
For more information, please visit the EACS website.
Indications and Usage for PIFELTRO and DELSTRIGO
PIFELTRO 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 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.
Selected Safety Information about PIFELTRO and DELSTRIGO
Warning: Posttreatment Acute Exacerbation of Hepatitis B (HBV)
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.
DELSTRIGO is contraindicated in patients with a previous hypersensitivity reaction to lamivudine.
Renal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. DELSTRIGO should be avoided with concurrent or recent use of a nephrotoxic agent (eg, high-dose or multiple NSAIDs). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in patients with risk factors for renal dysfunction who appeared stable on TDF.
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 clinical trials in HIV-1 infected adults, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher. Cases of osteomalacia associated with proximal renal tubulopathy have been reported with the use of TDF.
Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment.
Because DELSTRIGO is a complete regimen, co-administration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.
Co-administration of PIFELTRO with efavirenz, etravirine, or nevirapine is not recommended.
If DELSTRIGO is co-administered with rifabutin, take one tablet of DELSTRIGO once daily, followed by one tablet of doravirine (PIFELTRO) approximately 12 hours after the dose of DELSTRIGO.
If PIFELTRO is co-administered with rifabutin, increase PIFELTRO dosage to one tablet twice daily (approximately 12 hours apart).
Consult the full Prescribing Information prior to and during treatment for more information on potential drug-drug interactions.
Because DELSTRIGO is a fixed-dose combination tablet and the dosage of lamivudine and TDF cannot be adjusted, DELSTRIGO is not recommended in patients with estimated creatinine clearance less than 50 mL/min.
The most common adverse reactions with DELSTRIGO (incidence ≥5%, all intensities) were dizziness (7%), nausea (5%), and abnormal dreams (5%). The most common adverse reactions with PIFELTRO (incidence ≥5%, all intensities) were nausea (7%), dizziness (7%), headache (6%), fatigue (6%), diarrhea (6%), abdominal pain (5%), and abnormal dreams (5%).
The safety of DELSTRIGO in virologically-suppressed adults was based on Week 48 data from subjects in the DRIVE-SHIFT trial. Overall, the safety profile in virologically-suppressed adult subjects was similar to that in subjects with no ARV treatment history.
Serum ALT and AST Elevations: In the DRIVE-SHIFT trial, 22% and 16% of subjects in the immediate switch group experienced ALT and AST elevations greater than 1.25 X ULN, respectively, through 48 weeks on DELSTRIGO. For these ALT and AST elevations, no apparent patterns with regard to time to onset relative to switch were observed. One percent of subjects had ALT or AST elevations greater than 5 X ULN through 48 weeks on DELSTRIGO. The ALT and AST elevations were generally asymptomatic, and not associated with bilirubin elevations. In comparison, 4% and 4% of subjects in the delayed switch group experienced ALT and AST elevations of greater than 1.25 X ULN through 24 weeks on their baseline regimen.
There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO or DELSTRIGO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
Mothers infected with HIV-1 should be instructed not to breastfeed if they are receiving PIFELTRO or DELSTRIGO due to the potential for HIV-1 transmission.
About Islatravir (MK-8591)
Islatravir is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) currently being evaluated in clinical trials for the treatment of HIV-1 infection in combination with other antiretrovirals, as well as for pre-exposure prophylaxis of HIV-1 infection as a single investigational agent, across a variety of formulations.
Our Commitment to HIV
For more than 30 years, Merck has been committed to scientific research and discovery in HIV, and we continue to be driven by the conviction that more medical advances are still to come. Our focus is on pursuing research that addresses unmet medical needs and helps people living with HIV and their communities. We remain committed to working hand-in-hand with our partners in the global HIV community to address the complex challenges that hinder continued progress.
For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA
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.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
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 2018 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
[i] Data Collection on Adverse Events of Anti-HIV Drugs study
Sarra S. Herzog