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Tivicay® and Celsentri® now included in the Essential Drug List in Russia

Both medicines expected to be available in HIV specialist treatment centers from 2018 onwards.

London, UK, Tuesday 24 October, 2017 – ViiV Healthcare, a global specialist HIV company with GSK, Pfizer Inc. and Shionogi Limited as shareholders, today announced that the Government of Russia has endorsed the earlier recommendation of the Commission on the formation of lists of medicines to include dolutegravir (Tivicay®) and maraviroc (Celsentri®) in the List of Life Needed and Essential Medicines (Essential Drug List, EDL) for 2018. Both medicines are now expected to be available in HIV specialist treatment centers from 2018 onwards.

According to recent official data, 658,000 people living with HIV were registered at the specialized centers in the Russian Federation to receive regular medical service, an increase of 13% compared to 2015. The Ministry of Health had established that increasing the coverage of therapy available was one of the key elements of a strategy aimed at improving the situation.[i]

Jacopo Andreose, VP Head of International, ViiV Healthcare said, “The inclusion of Tivicay and Celsentri in the EDL is the latest achievement as part of our global access strategy to support the response to the HIV epidemic. It will make a real difference to people living with HIV in Russia, providing them with important additional options to manage their condition.  This latest success is the result of our unwavering commitment to ensure innovative HIV treatments are available to benefit patients everywhere.”

Dolutegravir was approved by the FDA in 2013 and has been available in Russia since 2014 on private prescription. The medicine is currently available in over 100 countries worldwide with more than 500,000 PLHIV have receive dolutegravir as part of their HIV treatment regimen.[ii]

About dolutegravir

Dolutegravir (Tivicay) is an integrase strand transfer inhibitor (INSTI) for use in combination with other antiretroviral agents for the treatment of HIV. 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. Tivicay is approved in over 90 countries across North America, Europe, Asia, Australia, Africa and Latin America.

Trade marks are owned or licensed by the ViiV Healthcare group of companies.

Important Information about Tivicay (dolutegravir)

FDA Indication and Usage:  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.

Use of Tivicay in INSTI-experienced patients should be guided by the number and type of baseline INSTI substitutions.  The efficacy of Tivicay 50 mg twice daily is reduced in patients with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions including T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, or G193E/R.

Important Safety Information for Tivicay (dolutegravir)

Contraindication: Tivicay is contraindicated (1) in patients with previous hypersensitivity reaction to dolutegravir, and (2) in patients receiving dofetilide (antiarrhythmic) 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 characterized 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. Discontinue Tivicay and other suspect agents immediately 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 is contraindicated in patients who have experienced a hypersensitivity reaction to dolutegravir.

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 naïve adult subjects in any one trial receiving Tivicay in a combination regimen were insomnia (3%), fatigue (2%), 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.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Tivicay/pdf/TIVICAY-PI-PIL.PDF.  

 

About Maraviroc

Maraviroc is the first chemokine (C-C motif) co-receptor 5 (CCR5) antagonist approved for use in treating HIV and has been available for use in the US, Europe, and other areas since 2007. Its unique mechanism is host-targeted, binding the CCR5 receptor and blocking viral entry into CD4+ cells.Maraviroc is one of the few agents that works before the virus enters the cell.

 

INDICATION AND USAGE

CELSENTRI, in combination with other antiretroviral medicinal products, is indicated for treatment-experienced adults, adolescents and children of 2 years of age and older and weighing at least 10 kg infected with only CCR5-tropic HIV-1 detectable.

Before taking CELSENTRI it has to be confirmed that only CCR5-tropic HIV-1 is detectable (i.e. CXCR4 or dual/mixed tropic virus not detected) using an adequately validated and sensitive detection method on a newly drawn blood sample. The Monogram Trofile assay was used in the clinical studies of CELSENTRI. The viral tropism cannot be safely predicted by treatment history and assessment of stored samples:

  • In Adults the recommended dose of CELSENTRI is 150 mg (with potent CYP3A inhibitor with or without a potent CYP3A inducer), 300 mg (without potent CYP3A inhibitors or inducers) or 600 mg twice daily (with potent CYP3A inducer without a potent CYP3A inhibitor) depending on interactions with concomitant antiretroviral therapy and other medicinal products.
  • In Children from 2 years of age and weighing at least 10kg, the recommended dose of CELSENTRI should be based on body weight (kg) and should not exceed the recommended adult dose. If a child is unable to reliably swallow CELSENTRI tablets, the oral solution (20 mg per mL) should be prescribed.
  • The recommended dose of CELSENTRI differs depending on interactions with concomitant antiretroviral therapy and other medicinal products. Refer to section 4.5 for corresponding adult dosage

 

CONTRAINDICATION

Hepatic disease

The safety and efficacy of maraviroc have not been specifically studied in patients with significant underlying liver disorders. Cases of hepatotoxicity and hepatic failure with allergic features have been reported in association with maraviroc. Hepatobiliary disorders reported in treatment-naïve patients were uncommon and balanced between treatment groups. Patients with pre-existing liver dysfunction, including chronic active hepatitis, can have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.

Discontinuation of maraviroc should be strongly considered in any patient with signs or symptoms of acute hepatitis, in particular if drug-related hypersensitivity is suspected or with increased liver transaminases combined with rash or other systemic symptoms of potential hypersensitivity (e.g. pruritic rash, eosinophilia or elevated IgE).

There are limited data in patients with hepatitis B and/or C virus co-infection. Caution should be exercised when treating these patients. In case of concomitant antiviral therapy for hepatitis B and/or C, please refer to the relevant product information for these medicinal products. There is limited experience in patients with reduced hepatic function, therefore maraviroc should be used with caution in this population

Severe skin and hypersensitivity reactions

Discontinue maraviroc and other suspect agents immediately if signs or symptoms of severe skin or hypersensitivity reactions develop. Clinical status and relevant blood chemistry should be monitored and appropriate symptomatic therapy initiated.

Cardiovascular safety

Limited data exist with the use of maraviroc in patients with severe cardiovascular disease, therefore special caution should be exercised when treating these patients with maraviroc. In the pivotal studies of treatment-experienced patients coronary heart disease events was more common in patients treated with maraviroc than with placebo (11 during 609 PY vs 0 during 111 PY of follow-up). In treatment-naïve patients such events occurred at a similarly low rate with maraviroc and control (efavirenz

Postural hypotension

When maraviroc was administered in studies with healthy volunteers at doses higher than the recommended dose, cases of symptomatic postural hypotension were seen at a greater frequency than with placebo. Caution should be used when administering maraviroc in patients on concomitant medicinal products known to lower blood pressure. Maraviroc should also be used with caution in patients with severe renal insufficiency and in patients who have risk factors for, or have a history of postural hypotension. Patients with cardiovascular co-morbidities could be at increased risk of cardiovascular adverse reactions triggered by postural hypotension.

Renal impairment

An increased risk of postural hypotension may occur in patients with severe renal insufficiency who are treated with potent CYP3A inhibitors or boosted protease inhibitors (PIs) and maraviroc. This risk is due to potential increases in maraviroc maximum concentrations when maraviroc is co-administered with potent CYP3A inhibitors or boosted PIs in these patients

Immune reconstitution syndrome

In HIV infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of CART.

Interaction with other medicinal products and other forms of interaction

Maraviroc is a substrate of cytochrome P450 CYP3A4. Co-administration of maraviroc with medicinal products that induce CYP3A4 may decrease maraviroc concentrations and reduce its therapeutic effects. Co-administration of maraviroc with medicinal products that inhibit CYP3A4 may increase maraviroc plasma concentrations. Dose adjustment of maraviroc is recommended when maraviroc is co-administered with potent CYP3A4 inhibitors and/or inducers

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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 and for people who are at risk of becoming infected with HIV. Shionogi joined 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 innovative medicines for HIV treatment and prevention, 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.

 

ViiV Healthcare Media enquiries:

Isabelle Scali

+44 (0) 208 0474733

 

Patricia O’Connor

+44 (0) 20 8047 5982

 

Marc Meachem

+1 919 949 3070

 

 

 

 

References

[i]https://www.rosminzdrav.ru/news/2017/05/16/5440-informatsiya-minzdrava-rossii-otnositelno-sluchaev-vich-v-rossii-po-itogam-2016-goda. Last accessed Sept 2017.

[ii] ViiV Healthcare. Data on File. 2017.