Merck Marks 30-Year Milestone in Commitment to Innovation and Care in HIV/AIDS
July 21, 2015 7:00 am ET
Unveils “Positively Committed” Campaign at International AIDS Society Conference
Merck (NYSE:MRK), known as MSD outside the United States and Canada,
announced today that the company’s commitment to HIV and AIDS, which
started with a research and development program initiated in the
mid-1980s during the early years of the epidemic, is now entering its
fourth decade. To commemorate Merck’s 30 years of commitment in this
area, the company is launching a new effort, “Positively Committed.”
The campaign highlights the company’s contributions, including the
development of innovative therapies to address the unmet medical needs
of people infected with HIV-1.
“The global health community has made significant progress in the fight
against HIV and Merck is proud of our role in this fight, starting at
the outset of the epidemic, and continuing to this day,” said Daria J.
Hazuda, vice president and therapeutic area head, infectious disease and
vaccines. “Although antiretroviral therapy has advanced the management
of HIV-1, much work remains to be done. We will continue to collaborate
with scientists, clinicians, patient advocates and the global health
community as we work together towards a common goal of eradicating this
Legacy of Commitment
In the mid-1980s, soon after the public health community first coined
the term “AIDS” to describe this emerging epidemic, Merck began its
HIV/AIDS research. Merck researchers were the first to describe the
chemical structure of the protease enzyme, and published the findings
immediately to encourage further research efforts. Merck researchers
then developed CRIXIVAN® (indinavir sulfate), an HIV
protease inhibitor, which was approved by the European Medicines
Agency and the U.S. Food and Drug Administration (FDA) in 1996. At the
time, the FDA’s approval of CRIXIVAN (indinavir sulfate) was the
fastest approval in FDA history.
In 1997, Merck’s clinical study of CRIXIVAN was the first to show that
a combination of antiretroviral medicines could provide prolonged
suppression of HIV RNA. Today, CRIXIVAN in combination with
antiretroviral agents is indicated for the treatment of HIV infection.
In 1999, Merck introduced efavirenz, a non-nucleoside
reverse-transcriptase inhibitor (NNRTI), which was developed by Merck
and DuPont Pharmaceuticals. Merck retained the rights to market
efavirenz in select markets outside the U.S. Today, efavirenz is one
of the most commonly prescribed antiretroviral therapies worldwide.
In the early 1990s, Merck was the first to demonstrate that inhibition
of the HIV-1 integrase enzyme—which is required for HIV
replication—was possible, and that inhibiting the integrase protein
reduced replication and spread of the virus. This research advancement
led to the development of ISENTRESS® (raltegravir). In
2007, the approval of ISENTRESS introduced a new class of treatments,
HIV-1 integrase strand transfer inhibitors. Today, ISENTRESS is
indicated in combination with other antiretroviral agents for the
treatment of HIV-1 infection in patients four weeks of age and older.
The use of other active agents with ISENTRESS is associated with a
greater likelihood of treatment response.
In addition, since the mid-1980s shortly after the HIV virus was
identified, Merck pursued one of the largest HIV vaccine research
programs, culminating in a large-scale trial that illustrated the
difficulty of developing a successful HIV vaccine.
Merck’s research efforts today include programs to develop novel HIV
treatment and prevention technologies, and collaborations on approaches
to address HIV latency and eradication.
Research is only one part of our comprehensive strategy to address unmet
needs in HIV. Merck also has sought to increase access to our HIV
medicines, particularly in resource limited settings.
“Effective treatments for HIV-1 infection were a distant hope in the
1980s, but collaborative scientific discovery and effective advocacy
have made them possible today,” said Dr. Julie Gerberding, executive
vice president, strategic communications, global public policy, and
population health at Merck. “I’m proud that Merck is committed to
sustaining our contributions to the treatment of this infection around
Addressing the Challenge of HIV/AIDS through Collaboration
Since the inception of its HIV/AIDS research program 30 years ago, Merck
has recognized the global impact of HIV/AIDS in developing countries
where economic, social and political factors impede access to education,
care and treatment. The Merck Foundation has partnered with governments,
non-governmental organizations and various other stakeholders,
contributing more than $122 million over the past 15 years to support
intervention programs, strengthen healthcare capacity and improve access
to treatment. In addition, Merck has provided access strategies, such as
differential pricing and voluntary licensing, to enhance access to
treatment in these communities.
This year, Merck partnered with the Medicines Patent Pool to provide
access to raltegravir for infants and children from four weeks to under
12 years of age in low- and middle-income developing countries.
Ongoing Commitment Continues
Merck’s steadfast dedication to patients living with HIV continues, and
is a part of our broader, sustained commitment to developing medicines
and vaccines to fight a broad range of infectious diseases.
Selected Safety Information for ISENTRESS (raltegravir)
Severe, potentially life-threatening and fatal skin reactions have been
reported. This includes cases of Stevens-Johnson syndrome,
hypersensitivity reaction and toxic epidermal necrolysis. Immediately
discontinue treatment with ISENTRESS and other suspect agents if severe
hypersensitivity, severe rash, or rash with systemic symptoms or liver
aminotransferase elevations develops and monitor clinical status,
including liver aminotransferases closely.
Immune reconstitution syndrome can occur, including the occurrence of
autoimmune disorders with variable time to onset, which may necessitate
further evaluation and treatment.
ISENTRESS chewable tablets contain phenylalanine, a component of
aspartame, which may be harmful to patients with phenylketonuria.
Coadministration of ISENTRESS with drugs that are strong inducers of
uridine diphosphate glucuronosyltransferase (UGT) 1A1 may result in
reduced plasma concentrations of raltegravir. Coadministration of
ISENTRESS (raltegravir) with drugs that inhibit UGT1A1 may increase
plasma levels of raltegravir.
Coadministration of ISENTRESS and other drugs may alter the plasma
concentration of raltegravir. The potential for drug-drug interactions
must be considered prior to and during therapy. Coadministration or
staggered administration of aluminum and/or magnesium
hydroxide-containing antacids and ISENTRESS is not recommended.
Rifampin, a strong inducer of UGT1A1, reduces plasma concentrations of
ISENTRESS. Therefore, the dose of ISENTRESS for adults should be
increased to 800 mg twice daily during coadministration with rifampin.
There are no data to guide coadministration of ISENTRESS with
rifampin in patients below 18 years of age.
The most commonly reported (≥2%) drug-related clinical adverse reactions
of moderate to severe intensity in treatment-naïve adult patients
receiving ISENTRESS compared with efavirenz were insomnia (4% vs 4%),
headache (4% vs 5%), nausea (3% vs 4%), fatigue (2% vs 3%), and
dizziness (2% vs 6%) respectively. In treatment-experienced adult
patients receiving ISENTRESS, the most commonly reported (≥2%)
drug-related clinical adverse reactions of moderate to severe intensity
and at a higher incidence compared with placebo was headache (2% vs
<1%). In both studies, intensities were defined as: Moderate (discomfort
enough to cause interference with usual activity); or Severe
(incapacitating with inability to work or do usual activity). In
treatment-experienced pediatric patients 4 weeks through 18 years of age
receiving ISENTRESS, the frequency, type and severity of drug-related
adverse reactions were comparable to those observed in adults.
Grade 2-4 creatine kinase laboratory abnormalities were observed in
subjects treated with ISENTRESS. Myopathy and rhabdomyolysis have been
reported. Use with caution in patients at increased risk of myopathy or
rhabdomyolysis, such as patients receiving concomitant medications known
to cause these conditions and patients with a history of rhabdomyolysis,
myopathy or increased serum creatine kinase.
Rash occurred more commonly in treatment-experienced subjects receiving
regimens containing ISENTRESS + darunavir/ritonavir compared to subjects
receiving ISENTRESS without darunavir/ritonavir or darunavir/ritonavir
without ISENTRESS. However, rash that was considered drug related
occurred at similar rates for all 3 groups. These rashes were mild to
moderate in severity and did not limit therapy; there were no
discontinuations due to rash.
ISENTRESS should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. There are no
adequate and well-controlled studies in pregnant women. In addition,
there have been no pharmacokinetic studies conducted in pregnant
To monitor maternal-fetal outcomes of pregnant patients exposed to
ISENTRESS, an Antiretroviral Pregnancy Registry has been established.
Physicians are encouraged to register patients by calling 1-800-258-4263.
About ISENTRESS (raltegravir)
ISENTRESS is Merck’s integrase inhibitor for the treatment of HIV-1
infection in adult and pediatric patients ages four weeks and older and
weighing at least 3 kg as part of combination HIV therapy. ISENTRESS
works by inhibiting the insertion of HIV-1 DNA into human DNA by the
integrase enzyme and has demonstrated rapid antiviral activity.
Inhibiting integrase from performing this essential function limits the
ability of the virus to replicate and infect new cells. ISENTRESS is now
approved as part of combination therapy in more than 76 countries for
use in treatment-naïve adult patients with HIV-1 and in more than 115
countries for use in treatment-experienced adult patients with HIV-1.
ISENTRESS, in combination therapy, for use in children and adolescents
with HIV-1 ages two years and older has also been approved for use in 46
countries, and ISENTRESS oral suspension for infants at least four weeks
of age is approved for use in 31 countries. Merck is continuing to move
forward with filings of ISENTRESS for oral suspension in additional
countries around the world. Please refer to the Prescribing Information
for ISENTRESS for information about dosage and administration for each
Selected Safety Information for CRIXIVAN (indinavir sulfate)
CRIXIVAN is contraindicated in patients with clinically significant
hypersensitivity to any of its components. CRIXIVAN, a CYP3A4 inhibitor,
also is contraindicated with the following drugs due to the potential
for elevated plasma concentrations of these drugs, which may lead to
serious and/or life-threatening reactions: alfuzosin, amiodarone,
dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride,
lovastatin, simvastatin, pimozide, Revatio (sildenafil, for treatment of
pulmonary arterial hypertension), oral midazolam, triazolam, alprazolam.
ALERT: Find out about medicines that should NOT be taken with
Nephrolithiasis/urolithiasis has occurred with therapy with CRIXIVAN.
The cumulative frequency of nephrolithiasis is substantially higher in
pediatric patients (29%) than in adult patients (12.4%; range across
individual trials: 4.7%–34.4%). The cumulative frequency of
nephrolithiasis events increases with increasing exposure to CRIXIVAN;
however, the risk over time remains relatively constant. In some cases,
nephrolithiasis/urolithiasis has been associated with renal
insufficiency or acute renal failure, pyelonephritis with or without
bacteremia. If signs or symptoms of nephrolithiasis/urolithiasis occur
(including flank pain, with or without hematuria or microscopic
hematuria), temporary interruption (e.g., 1–3 days) or discontinuation
of therapy may be considered. Adequate hydration is recommended in
all patients treated with CRIXIVAN (indinavir sulfate).
Acute hemolytic anemia, including cases resulting in death, has been
reported in patients treated with CRIXIVAN. Once a diagnosis is
apparent, appropriate measures for the treatment of hemolytic anemia
should be instituted, including discontinuation of CRIXIVAN.
Hepatitis including cases resulting in hepatic failure and death has
been reported in patients treated with CRIXIVAN. Because the majority of
these patients had confounding medical conditions and/or were receiving
concomitant therapy(ies), a causal relationship between CRIXIVAN and
these events has not been established.
New onset diabetes mellitus, exacerbation of pre-existing diabetes
mellitus and hyperglycemia have been reported during post-marketing
surveillance in HIV-infected patients receiving protease inhibitor
therapy. Some patients required either initiation or dose adjustments of
insulin or oral hypoglycemic agents for treatment of these events. In
some cases, diabetic ketoacidosis has occurred. In those patients who
discontinued protease inhibitor therapy, hyperglycemia persisted in some
Initiation of CRIXIVAN, a CYP3A inhibitor, in patients receiving
medications metabolized by CYP3A or initiation of medications
metabolized by CYP3A in patients already receiving CRIXIVAN, may
increase plasma concentrations of medications metabolized by CYP3A.
Initiation of medications that inhibit or induce CYP3A may increase or
decrease concentrations of CRIXIVAN, respectively. These interactions
may lead to:
Clinically significant adverse reactions, potentially leading to
severe, life-threatening, or fatal events from greater exposures of
Clinically significant adverse reactions from greater exposures of
Loss of therapeutic effect of CRIXIVAN and possible development of
Consider the potential for drug interactions prior to and during
CRIXIVAN therapy; review concomitant medications during CRIXIVAN
therapy; and monitor for the adverse reactions associated with the
Caution should be exercised if CRIXIVAN is used concurrently with
atorvastatin or rosuvastatin. Titrate the atorvastatin and rosuvastatin
doses carefully and use the lowest necessary dose with CRIXIVAN. Caution
should be used with coadministration of CRIXIVAN and parenteral
midazolam. Particular caution should be used when prescribing
sildenafil, tadalafil, or vardenafil in patients receiving indinavir.
Coadministration of CRIXIVAN with these medications is expected to
substantially increase plasma concentrations of sildenafil, tadalafil,
and vardenafil and may result in an increase in adverse events,
including hypotension, visual changes, and priapism, which have been
associated with sildenafil, tadalafil, and vardenafil.
Concomitant use of CRIXIVAN (indinavir sulfate) and St. John’s Wort
(Hypericum perforatum) or products containing St. John’s Wort is not
recommended. Coadministration of CRIXIVAN and St. John’s Wort has been
shown to substantially decrease indinavir concentrations and may lead to
loss of virologic response and possible resistance to CRIXIVAN or to the
class of protease inhibitors.
Indirect hyperbilirubinemia has occurred frequently during treatment
with CRIXIVAN and has infrequently been associated with increases in
Reports of tubulointerstitial nephritis with medullary calcification and
cortical atrophy have been observed in patients with asymptomatic severe
leukocyturia (>100 cells/high-power field). Patients with asymptomatic
severe leukocyturia should be followed closely and monitored frequently
with urinalyses. Further diagnostic evaluation may be warranted, and
discontinuation of CRIXIVAN should be considered in all patients with
Immune reconstitution syndrome has been reported in patients treated
with combination antiretroviral therapy, including CRIXIVAN. During the
initial phase of combination antiretroviral treatment, patients whose
immune system responds may develop an inflammatory response to indolent
or residual opportunistic infections (such as Mycobacterium avium
infection, cytomegalovirus, Pneumocystis jiroveci pneumonia (PCP), or
tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, and
Guillain-Barré syndrome) have also been reported to occur in the setting
of immune reconstitution; however, the time of onset is more variable,
and can occur many months after initiation of treatment.
There have been reports of spontaneous bleeding in patients with
hemophilia A and B treated with protease inhibitors.
In patients with hepatic insufficiency due to cirrhosis, the dosage of
CRIXIVAN should be lowered because of decreased metabolism of CRIXIVAN.
Patients with renal insufficiency have not been studied.
Redistribution/accumulation of body fat including central obesity,
dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial
wasting, breast enlargement, and “cushingoid appearance” have been
observed in patients receiving antiretroviral therapy. The mechanism and
long-term consequences of these events are currently unknown. A causal
relationship has not been established.
CRIXIVAN should not be coadministered with rifampin. Coadministration of
CRIXIVAN with rifampin may lead to loss of virologic response and
possible resistance to CRIXIVAN or to the class of protease inhibitors
or other coadministered antiretroviral agents.
Coadministration of CRIXIVAN with atazanavir is not recommended. Both
drugs are associated with indirect (unconjugated) hyperbilirubinemia.
Combinations of these drugs have not been studied.
Alteration in dose or regimen with various HIV antiviral agents or other
agents may be recommended based on drug interaction studies or predicted
interaction. See Table 9 of the Precautions, Drug Interactions Section
of the Prescribing Information for details.
There are no adequate and well-controlled studies in pregnant patients.
CRIXIVAN should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. To monitor maternal-fetal
outcomes of pregnant patients exposed to CRIXIVAN, an Antiretroviral
Pregnancy Registry has been established. Physicians are encouraged to
register patients by calling 1-800-258-4263.
Selected adverse reactions of severe or life-threatening intensity and
of unknown drug relationship reported by patients treated with
CRIXIVAN/AZT/3TC in ACTG 320 were: fever (3.8%), nausea (2.8%),
nephrolithiasis/urolithiasis (2.6%), headache (2.4%), asthenia/fatigue
(2.4%), anemia (2.4%), abdominal pain (1.9%), difficulty
breathing/dyspnea/shortness of breath (1.8%), cough (1.6%), vomiting
(1.4%), rash (1.1%), back pain (0.9%), and diarrhea (0.9%).
About CRIXIVAN (indinavir sulfate)
CRIXIVAN 200 mg and 400 mg capsules in combination with antiretroviral
agents are indicated for the treatment of HIV infection. This indication
is based on two clinical trials of approximately one year duration that
demonstrated: 1) a reduction in the risk of AIDS-defining illnesses or
death; 2) a prolonged suppression of HIV RNA. CRIXIVAN does not cure HIV
infection, does not reduce the transmission of HIV, and should only be
taken in combination with other drugs for HIV. Please refer to the
Prescribing Information for CRIXIVAN for information about dosage and
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subject to significant risks and uncertainties. If underlying
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actual results may differ materially from those set forth in the
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by competitors; challenges inherent in new product development,
including obtaining regulatory approval; the company’s ability to
accurately predict future market conditions; manufacturing difficulties
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The company undertakes no obligation to publicly update any
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statements can be found in the company’s 2014 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 ISENTRESS (raltegravir) at http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_pi.pdf,
Patient Information for ISENTRESS at http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_ppi.pdf
and Instructions for Use of ISENTRESS (raltegravir) for Oral Suspension
Please see Prescribing Information for CRIXIVAN (indinavir sulfate)
and Patient Information for CRIXIVAN at http://www.merck.com/product/usa/pi_circulars/c/crixivan/crixivan_ppi.pdf
Brand names used are trademarks of their respective owners.
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