Merck (NYSE: MRK), known as MSD outside the United States and
Canada, announced today upcoming presentations of new analyses from
its HIV clinical development program during the 23rd International
AIDS Conference (AIDS 2020: Virtual) taking place virtually from
July 6-10, 2020. The presentations include Week 48 safety and
virologic failure data from the Phase 2b trial evaluating
islatravir, the company’s investigational nucleoside reverse
transcriptase translocation inhibitor (NRTTI), with doravirine, the
company’s non-nucleoside reverse transcriptase inhibitor (NNRTI),
in adults with HIV-1 infection who had not previously received
antiretroviral treatment. The data presentations also include a
post-hoc analysis of weight change from the Phase 3 DRIVE-SHIFT
trial evaluating the effect of switching to DELSTRIGO™
(doravirine/lamivudine/tenofovir disoproxil fumarate) as well as an
examination from the OPERA cohort of weight changes in people
living with HIV.
“Today, the importance of combating infectious diseases is more
apparent than ever, and for more than 30 years, Merck has been
striving for a world without HIV by working on innovations that
have helped define better treatment pathways for those living with
HIV,” said Dr. Joan Butterton, vice president, infectious diseases,
Global Clinical Development, Merck Research Laboratories. “We look
forward to sharing new data from our doravirine and islatravir
programs at AIDS 2020, and further understanding their clinical
potential in helping to address unmet medical needs facing the HIV
community.”
Select abstracts in the AIDS 2020 program include:
- Islatravir Safety Analysis Through Week 48 From A Phase 2 Trial
in Treatment Naïve Adults With HIV-1 Infection. Oral Presentation.
Presentation OAB0305. E. DeJesus et al.
- Analysis of Protocol Defined Virologic Failure Through Week 48
From A Phase 2 Trial (P011) Of Islatravir And Doravirine In
Treatment-Naïve Adults With HIV-1 Infection. Oral Presentation.
Presentation OAB0302. C. Orkin et al.
- Weight Changes After Switching to Doravirine/Lamivudine/TDF in
the DRIVE-SHIFT Trial. Oral Presentation. Presentation OAB0605. P.
Kumar et al.
- Weight Gain Before and After Switch from TDF to TAF. Oral
Presentation. Presentation OAB0604. P. Mallon et al.
- Doravirine Resistance Profile in Clinical Isolates and Impact
of Baseline NNRTI Resistance-Associated Mutations Observed in
Treatment-Naïve Participants from Phase 3 Clinical Trials. Poster
Presentation. Presentation PDB0406. E. Asante-Appiah et al.
- Dose Adjustment of Doravirine Mitigates the Pharmacokinetic
Interaction With the Moderate CYP3A Inducer, Rifabutin. Poster
Presentation. Presentation PEA0083. S. Kalilieh et al.
- Cardiovascular and Metabolic Comorbidities in HIV Patients in
Colombia: A Multicenter Study. Poster Presentation. Presentation
PEB0180. S. Valderrama-Beltrán et al.
For more information, including details around the virtual
programming, please visit the AIDS 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 (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%).
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 recent 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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