Researchers Will Present Week 96 Data from
Phase 2b Study Evaluating Islatravir in Combination with
Doravirine, and Phase 1/1b Data for MK-8507, an Investigational
NNRTI for the Treatment of HIV-1 Infection
Company Plans to Advance MK-8507 into Phase
2 Evaluating its Efficacy and Safety in Combination with Islatravir
as a Once-Weekly Oral Regimen
Merck (NYSE: MRK), known as MSD outside the United States and
Canada, announced today that nine abstracts from the company’s
diverse HIV portfolio and pipeline will be presented at the 2020
International Congress on Drug Therapy in HIV Infection (HIV
Glasgow 2020, October 5-8, 2020). During the congress, researchers
will present new data from Merck’s HIV development program,
including 96-week results from efficacy and safety analyses from
the Phase 2b study of islatravir (Merck’s investigational
nucleoside reverse transcriptase translocation inhibitor (NRTTI))
in combination with doravirine (PIFELTRO™) in adults with HIV-1
infection who had not previously received antiretroviral treatment.
Additionally, Merck will share results from Phase 1/1b studies of
MK-8507, an investigational oral non-nucleoside reverse
transcriptase inhibitor (NNRTI) under development for once-weekly
oral administration in combination with islatravir. These and other
data, including 144-week results from the Phase 3 DRIVE-SHIFT study
evaluating the effect of switching from a stable antiretroviral
therapy (ART) regimen to DELSTRIGO™
(doravirine/lamivudine/tenofovir disoproxil fumarate), will be
shared via oral and poster presentations during the virtual
congress.
“Merck remains at the forefront of research to develop new
medicines for people living with HIV. The new data we will present
at HIV Glasgow 2020 from our HIV research programs – for
doravirine, islatravir, and now MK-8507 – demonstrate our sustained
innovation and unwavering commitment to help address the global
burden of HIV,” said Dr. Joan Butterton, vice president, infectious
diseases, Global Clinical Development, Merck Research Laboratories.
“Our plans to evaluate MK-8507 as a potential partner with
islatravir, as well as the ongoing clinical trials of islatravir
and doravirine, illustrate the diversity of candidates in our HIV
pipeline and our quest to transform the way HIV is treated.”
Select abstracts in the HIV Glasgow 2020 program include:
- Islatravir in combination with doravirine maintains HIV-1 viral
suppression through 96 weeks. Oral Presentation O415. Abstract
4913173. J.M. Molina et al.
- Renal safety through 96 weeks from a phase 2 trial (P011) of
islatravir and doravirine in treatment-naïve adults with HIV-1.
Poster Presentation P048. Abstract 4919993. F. Post et al.
- Analysis of protocol defined virologic failure through 96 weeks
from a phase 2 trial (P011) of islatravir and doravirine in
treatment-naïve adults with HIV-1. Poster Presentation P047.
Abstract 4913025. C. Orkin et al.
- Long-term treatment safety and efficacy following switch to
doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF):
Week 144 results of the DRIVE-SHIFT trial. Poster Presentation
P037. Abstract 4922614. P. Kumar et al.
- Single doses of MK-8507, a novel HIV-1 NNRTI, reduced HIV viral
load for at least a week. Oral Presentation O416. W. Ankrom et
al.
- Safety, tolerability and pharmacokinetics following single- and
multiple-dose administration of the novel NNRTI MK-8507 with a
midazolam interaction arm. Poster Presentation P099. Abstract
4913210. W. Ankrom et al.
- Islatravir Selects for HIV-1 Variants in MT4-GFP cells that
Profoundly Reduce Replicative Capacity in PBMCs and Reduce
Susceptibility to Islatravir but not NRTIs. Poster Presentation
P120. Abstract 4920686. T. Diamond et al.
For more information, including details around the virtual
programming, please visit the HIV Glasgow 2020 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 (e.g., 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%).
By Week 96 in DRIVE-FORWARD, 2% of adult subjects in the
PIFELTRO group and 3% in the DRV+r group had adverse events leading
to discontinuation of study medication.
By Week 96 in DRIVE-AHEAD, 3% of adult subjects in the DELSTRIGO
group and 7% in the EFV/FTC/TDF group had adverse events leading to
discontinuation of study medication.
In DRIVE-FORWARD, mean changes from baseline at Week 48 in
LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) were
pre-specified. LDL-C: -4.6 mg/dL in the PIFELTRO group vs 9.5 mg/dL
in the DRV+r group. Non-HDL-C: -5.4 mg/dL in the PIFELTRO group vs
13.7 mg/dL in the DRV+r group. The clinical benefits of these
findings have not been demonstrated.
In DRIVE-AHEAD, mean changes from baseline at Week 48 in
LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) were
pre-specified. LDL-C: -2.1 mg/dL in the DELSTRIGO group vs 8.3
mg/dL in the EFV/FTC/TDF group. Non-HDL-C: -4.1 mg/dL in the
DELSTRIGO group vs 12.7 mg/dL in the EFV/FTC/TDF group. The
clinical benefits of these findings have not been demonstrated.
In DRIVE-SHIFT, mean changes from baseline at Week 48 in
LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) were
pre-specified. LDL-C: -16.3 mg/dL in the DELSTRIGO group vs -2.6
mg/dL in the PI + ritonavir group. Non-HDL-C: -24.8 mg/dL DELSTRIGO
group vs -2.1 mg/dL in the PI + ritonavir group. The clinical
benefits of these findings have not been demonstrated.
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.
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 (formerly MK-8591) 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 (PrEP) 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.
Our Commitment to Infectious Diseases
For more than 100 years, Merck has contributed to the discovery
and development of novel medicines and vaccines to combat
infectious diseases. In addition to a combined portfolio of
vaccines and antibacterial, antiviral and antifungal medicines,
Merck has multiple programs that span discovery through late-stage
development. To learn more about Merck’s infectious diseases
pipeline, visit www.merck.com.
About Merck
For more than 125 years, Merck, 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 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.
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 the global outbreak of novel coronavirus disease
(COVID-19); 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 2019
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
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