ViiV Healthcare announces new initiatives to improve access to dolutegravir: licence to the Medicines Patent Pool

LONDON, April 1, 2014 /PRNewswire/ -- ViiV Healthcare today announced new collaborations with the goal of increasing access to its HIV medicine, dolutegravir (marketed under the name Tivicay®), just two months after its approval by the European Medicines Agency (EMA) and eight months after approval by the US Food and Drug Administration (FDA). Through an agreement with the Medicines Patent Pool (MPP), ViiV Healthcare will accelerate access to dolutegravir where the need is the greatest, in the countries where 99% of children and 93.4% of adults with HIV in the developing world live.

"Our new collaborations prioritise dolutegravir access for millions of children and adults with HIV, and represent another step in our ongoing commitment to improving access and delivering innovation in the areas of highest unmet need," said Dr Dominique Limet, Chief Executive Officer, ViiV Healthcare. "We recognise that important new agents have the potential to make a real difference in resource poor settings. In fact, the World Health Organization has recently cited dolutegravir as a development priority for future anti-retroviral treatments for children–it is currently approved for children 12 years and older.ⁱ Therefore, accelerating access to medicines like dolutegravir is of the utmost importance."

Licence to the Medicines Patent Pool

In adults: The collaboration with MPP includes two distinct approaches to improve access for adults living with HIV in the developing world:  first, a royalty-free voluntary licence in all least-developed, all low-income and all sub-Saharan African countries; second, for specific middle-income countries including India, ViiV Healthcare has established the first-ever MPP licence with a tiered royalty structure, where a small percentage of the sale price is paid based on the gross domestic product (GDP) of the specific country. The licences will also allow for the possible development, manufacture and supply of dolutegravir-based fixed-dose combinations, including those with abacavir, if and when approved by local regulatory agencies.

Supporting children living with HIV: ViiV Healthcare will grant MPP a voluntary licence for generic manufacturers to develop paediatric formulations of dolutegravir without paying a royalty in 121 countries where most (99%) children with HIV live. Dolutegravir is currently approved for patients 12 years and older.  However, this licence also includes a commitment for future lower dose tablets and age-appropriate formulations developed by ViiV Healthcare to meet the needs of younger children with HIV, if and when approved by a major regulatory authority.    

Today's announcement complements an earlier voluntary licence for dolutegravir signed in 2013 with Aurobindo Pharma for adults and children for our standard voluntary licence territories. 

Our Approach to Improving Access: ViiV Healthcare is committed to improving access to medicines for people living with HIV through a variety of approaches, based on the differing needs of people living with HIV in different parts of the world.

• Royalty-free voluntary licences in those countries with the lowest incomes and/or hardest hit by the global epidemic: In 2010 ViiV Healthcare extended its royalty-free voluntary licensing policy, which includes the company's existing portfolio in all least-developed, all low-income and all sub-Saharan countries; home to 25 million people living with HIV (i.e., 75% of people living with HIV worldwide). These licences facilitate the manufacture and sale of low-cost versions of the company's medicines in those countries most affected by HIV and least able to pay for treatment and care. 
• Flexible pricing and local partnerships with generics manufacturers in middle-income countries (i.e., emerging and newly industrialised economies): In countries where incomes are higher and infrastructure is more developed, the flexible pricing policy factors in the GDP and the impact of the epidemic in each country to improve affordability. Local partnerships are approached on a case-by-case basis, taking into account the local needs and situation. One key approach is creating partnerships with in-country pharmaceutical companies to manufacture medicines locally in order to bring costs down, while simultaneously investing resources and expertise to build skills in the local economy. 

Our Commitment to Children Living with HIV: Approximately 3.3 million children are living with HIV worldwide, but 66% of those needing treatment do not have access to appropriate care and medicines. Among several barriers preventing further scale up of the numbers of children on treatment is the lack of low-cost medicines that are palatable and acceptable for use by childrenⁱⁱ. 

ViiV Healthcare is committed to improving scientific understanding and treatment options for infants and children living with HIV. This includes a broad range of initiatives supported through our Paediatric Innovation Seed Fund, which aims to improve paediatric HIV research, care and treatment in resource-limited settings. Additionally, the Positive Action for Children Fund supports 150 organisations across 30 countries to deliver programmes designed to prevent mother-to-child transmission of HIV.

Important Information about Tivicay® (dolutegravir)

FDA Indication and Usage in the US:  TIVICAY is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and children aged 12 years and older and weighing at least 40 kg. The following should be considered prior to initiating TIVICAY: poor virologic response was observed in subjects treated with TIVICAY 50 mg twice daily with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions including L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R.

Important Safety Information for Tivicay® (dolutegravir)

Contraindication: Co-administration of TIVICAY with dofetilide (anti-arrhythmic) is contraindicated due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events.

Hypersensitivity Reactions: Hypersensitivity reactions have been reported and were characterised by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in 1% or fewer subjects receiving TIVICAY in Phase 3 clinical trials. Immediately discontinue TIVICAY and other suspect agents if signs or symptoms of hypersensitivity reaction develop, (including but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing.) Monitor clinical status, including liver aminotransferases, and initiate appropriate therapy. Delay in stopping treatment with TIVICAY or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction. TIVICAY should not be used in patients who have experienced a hypersensitivity reaction to TIVICAY.

Effects on Serum Liver Biochemistries in Patients with Hepatitis B or C Coinfection: Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY. In some cases the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation particularly in the setting where anti-hepatitis therapy was withdrawn. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with TIVICAY are recommended in patients with underlying hepatic disease such as hepatitis B or C. 

Fat Redistribution: Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy.

Immune Reconstitution Syndrome: During the initial phase of treatment, immune reconstitution syndrome can occur, which may necessitate further evaluation and treatment. Autoimmune disorders have been reported to occur in the setting of immune reconstitution; the time to onset is more variable and can occur many months after initiation of treatment.

Adverse Reactions: The most commonly reported (≥2%) adverse reactions of moderate to severe intensity in treatment naive adult subjects in any one trial receiving TIVICAY in a combination regimen were insomnia (3%) and headache (2%). 

Drug Interactions: Co-administration of TIVICAY with drugs that are strong inducers of UGT1A1 and/or CYP3A4 may result in reduced plasma concentrations of dolutegravir and require dose adjustments of TIVICAY.

-TIVICAY should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.

-Consult the full Prescribing Information for TIVICAY for more information on potentially significant drug interactions, including clinical comments.

Pregnancy: Pregnancy category B. TIVICAY should be used during pregnancy only if the potential benefit justifies the potential risk. An Antiretroviral Pregnancy Registry has been established.

Breastfeeding: Breastfeeding is NOT recommended due to the potential for HIV transmission and the potential for adverse reactions in nursing infants.

Paediatric Patients: Safety and efficacy of TIVICAY has not been established in children younger than 12 years old, or weighing <40 kg, or in INSTI-experienced paediatric patients with documented or clinically suspected INSTI resistance.

Please visit the following link for the full US prescribing and patient information: https://www.viivhealthcare.com/media/58599/us_tivicay.pdf.   

About Tivicay®

Tivicay (dolutegravir) is an integrase inhibitor indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 in adults and children aged 12 years and older weighing at least 40 kg. Integrase inhibitors block HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection.

It is available as a small, yellow, 50 mg tablet. Importantly, it can be taken with or without food and at any time of the day.

Today's announcement follows the US Food and Drug Administration (FDA) approval of dolutegravir (Tivicay®) on 12 August 2013 and the European Medicines Agency (EMA) approval on 20 January 2014.  Dolutegravir is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 in adults and children aged 12 years and older.

Tivicay is the first new treatment delivered by ViiV Healthcare.

About ViiV Healthcare

ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV. Shionogi joined as a 10% shareholder in October 2012. The company's aim is to take a deeper and broader interest in HIV/AIDS than any company has done before and take a new approach to deliver effective and new HIV medicines, as well as support communities affected by HIV. For more information on the company, its management, portfolio, pipeline, and commitment, please visit www.viivhealthcare.com. 

ⁱ  "MARCH 2014 SUPPLEMENT TO THE 2013 CONSOLIDATED GUIDELINES ON THE USE OF ANTIRETROVIRAL DRUGS FOR TREATING AND PREVENTING HIV INFECTION. Recommendations for a public health approach." WHO. Web. 28 February 2014. http://www.who.int/hiv/pub/guidelines/arv2013/arvs2013upplement_march2014/en/.

ⁱⁱ "Global Report: UNAIDS report on the global AIDS epidemic 2013." UNAIDS. Web. 11 February 2014. http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf.

SOURCE ViiV Healthcare