From Merck:

Merck Announces Collaboration with the Medicines Patent Pool to Expand Access to Pediatric Formulations of Raltegravir in Developing Countries

Tuesday, February 24, 2015 3:00 am EST

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KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced an agreement with the Medicines Patent Pool (MPP) to license its pediatric formulations of raltegravir for use in treating HIV-1 infection in infants and children from four weeks to under 12 years of age in developing countries. This is the MPP’s first agreement to provide access to an HIV integrase inhibitor for use in combination HIV therapy for infants and children in this age range. The agreement also allows for development of novel pediatric formulations of raltegravir and novel combinations. Raltegravir is marketed by Merck as ISENTRESS^® (raltegravir). In the United States, ISENTRESS is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in patients four weeks of age and older.

“This agreement with the MPP has been established to provide access to raltegravir to HIV-infected children in developing countries where the burden of HIV infection is highest, including sub-Saharan Africa,” said Jackie Neilson, general manager and global commercial leader for the HIV Franchise, Merck. “This builds upon Merck’s three-decade long commitment to both innovation and access to address the global HIV epidemic.”

Raltegravir is the only integrase inhibitor approved for use in infants and children as young as four weeks in the United States and European Union. Pediatric formulations of raltegravir are available as chewable tablets (25 mg and 100 mg) and granules for oral suspension (single-use 100 mg packets).

Merck is providing the MPP a royalty-free license for the development of pediatric formulations of raltegravir—chewable tablets and granules for oral suspension—for infants and children from four weeks to under 12 years of age. The agreement is designed to improve access to raltegravir for pediatric populations in low- and middle-income countries with significantly high rates of pediatric HIV, totaling 92 countries. In addition to providing expanded access, the agreement allows for development of new pediatric formulations of raltegravir, in support of the “Global Pediatric Antiretroviral Commitment-to-Action” announced by the United States President’s Emergency Plan for AIDS Relief (PEPFAR), the Pediatric HIV Treatment Initiative (PHTI), and the Global Fund to Fight AIDS, Tuberculosis and Malaria, to accelerate the development of new, high-priority pediatric antiretroviral co-formulations.

“MPP is pleased to have Merck on board as a new private sector partner working with us on pediatric programs,” said Greg Perry, executive director, MPP. “Raltegravir adds to our arsenal of pediatric licenses in supporting better options for children in low- and middle-income countries and can benefit the most neglected sub-segment: infants and toddlers less than three years of age.”

Despite efforts to eliminate pediatric HIV, it is estimated that there are 3.2 million children infected with HIV worldwide and almost 800 die every day because of lack of access to treatment and care. In fact, it is estimated that less than a quarter of all children infected with HIV worldwide are receiving antiretrovirals. Therefore, it is critical to develop innovative formulations to meet this unmet medical need while ensuring access to these therapies. As such, the World Health Organization (WHO) guidelines have listed raltegravir as an important product needed for certain pediatric populations.

For 30 years, Merck has demonstrated its commitment to improved access to HIV medicines through longstanding efforts including differential pricing, voluntary licensing, public-private partnerships, philanthropic programs, and continued research and development efforts in HIV. For more information about Merck’s corporate responsibility in HIV, visitwww.merckresponsibility.com/access-to-health/infectious-diseases/hiv-aids/.

Selected Safety Information

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 (raltegravir) 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 (raltegravir) 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 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 (raltegravir) 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 patients.

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

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 (raltegravir) 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 (raltegravir) for oral suspension in additional countries around the world.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. 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 healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. 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; Merck’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 Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck 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 Merck’s 2013 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) athttp://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_pi.pdf, Patient Information for ISENTRESS athttp://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_ppi.pdf and Instructions for Use of ISENTRESS for Oral Suspension athttps://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_ifu.pdf.