Scottish Medicines Consortium Approves First-In-class Integrase Inhibitor,'Isentress'(R) (Raltegravir), For The Treatment Of HIV

Main Category: HIV / AIDS
Article Date: 13 May 2008 - 0:00 PDT

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The Scottish Medicines Consortium (SMC) announced that 'Isentress'® (raltegravir) has been accepted for restricted use within NHS Scotland in combination with other antiretroviral medicinal products agents for the treatment of Human Immunodeficiency Virus (HIV-1) infection in treatment-experienced adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. It is restricted to patients with triple class resistant HIV-1 infection.

Raltegravir is the first antiretroviral treatment to target the integrase enzyme, one of the three HIV enzymes required by the HIV virus in order to replicate (reproduce), the other two being reverse transcriptase and protease. Launched in the UK in January 2008 for use in combination with other antiretroviral medicinal products for the treatment of HIV-1 infection in treatment-experienced adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy, it is available as 400mg oral tablets.

Dr Clifford Leen, Consultant Physician at the Lothian University Hospitals NHS Trust, commented, "Today's announcement is extremely good news for people affected by HIV in Scotland. Healthcare professionals in Scotland now have access to this new treatment which represents an important step forward in our fight against HIV. With HIV infection on the rise in Scotland, it is important that treatment-experienced patients have appropriate access to novel therapies such as raltegravir."

Recent studies have shown that at 48 weeks raltegravir plus optimised background therapy (OBT - a regime of active antiretroviral drugs tailored to individual patients, chosen by their physicians as most likely to be of benefit), had superior antiretroviral and immunological efficacy compared to placebo plus OBT. In patients receiving raltegravir plus OBT, up to 89% achieved HIV viral load reduction to less than < 50 copies/mL at week 48.1,2

Dr Leen added, "HIV treatments are being placed under the same level of scrutiny by commissioners as drugs for other therapeutic areas such as cancer, from both cost and efficacy perspectives. The SMC approval for raltegravir therefore signifies its important place within the HIV treatment armoury."

The announcement comes on the back of the launch last month of new standards of practice for NHS sexual health services in Scotland, where sexually transmitted infections are reaching record levels.3 5,415 people have now been diagnosed as having HIV in Scotland.4 446 new cases of HIV were reported in 2007 in Scotland, with rising infections seen among both heterosexuals and homosexuals.5 This was the highest annual total since recording began in 1984 and a 29% increase on the 345 cases reported in 2006.5

Raltegravir (Isentress®) SMC advice

Raltegravir (Isentress®) is accepted for restricted use within NHS Scotland in combination with other antiretroviral medicinal products agents for the treatment of Human Immunodeficiency Virus (HIV-1) infection in treatment-experienced adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. It is restricted to patients with triple class resistant HIV-1 infection.

Addition of raltegravir to optimised background therapy in treatment experienced patients with documented resistance to at least one drug in each of the three HIV antiviral classes, significantly increased the number of patients achieving clinically significant reductions in viral load.

About the SMC

The Scottish Medicines Consortium (SMC) provides advice to NHS Boards and their Area Drug and Therapeutics Committees (ADTCs) across Scotland about the status of all newly licensed medicines, all new formulations of existing medicines and new indications for established products (licenced from January 2002). This advice will be made available as soon as practical after the launch of the product involved. The remit of SMC excludes the assessment of vaccines, branded generics, non-prescription-only medicines, blood products, plasma substitutes and diagnostic drugs. The review of device-containing medicines will be confined to those licensed as medicines by the MHRA/EMEA.

About 'Isentress'

Week 48 results of two identical, ongoing multicentre, double-blind randomised placebocontrolled Phase III studies (BENCHMRK-1 and BENCHMRK-2) were recently presented at the 15th Conference on Retroviruses and Opportunistic Infections (CROI), in Boston, USA.1,2 The studies involved approximately 700 patients and compared raltegravir in combination with optimised background therapy (OBT - a regime of active antiretroviral drugs tailored to individual patients, chosen by their physicians as most likely to be of benefit) to placebo plus OBT. In BENCHMRK-1, at 48 weeks, raltegravir plus OBT achieved HIV viral load reduction to less than 400 copies/mL in 74 percent of patients compared to 36 percent of patients receiving placebo plus OBT (p<0.001). In the companion study BENCHMRK-2 raltegravir plus OBT suppressed viral loads below 400 copies/mL in 71 percent of patients compared to 38 percent of patients receiving placebo plus OBT (p<0.001).

In addition, in BENCHMRK-1, after 48 weeks of therapy, raltegravir plus OBT suppressed viral load to below 50 copies/mL in 65 percent of patients compared to 31 percent of patients receiving placebo plus OBT (p<0.001). Raltegravir plus OBT increased CD4 cell counts from baseline by 120 cells/mm3 compared to 49 cells/mm3 for patients receiving placebo plus OBT (p<0.001). In BENCHMRK-2, after 48 weeks, 60 percent of patients receiving raltegravir plus OBT achieved viral loads below 50 copies/mL compared to 35 percent of patients receiving placebo plus OBT (p<0.001). Raltegravir plus OBT increased CD4 cell counts from baseline by 98 cells/mm3 compared to 40 cells/mm3 for those patients receiving placebo plus OBT (p<0.001).

For full prescribing information, including Clinical Particulars and Pharmacological Properties, please refer to the Summary of Product Characteristics included in this press kit. If the SPC is missing, please contact any of the individuals listed at the end of this release for a copy. 'Isentress'® is a Registered Trademark of Merck & Co., Inc., Whitehouse Station, New Jersey, USA The NHS price of 'Isentress' 400mg is £21.58 per day.

Viral Load

Viral load is the term used to describe the amount of HIV in the blood. A viral load above 100,000 copies/ml is considered high, and one below 10,000 copies/ml is considered low. A viral load below 50 copies/ml is said to be 'undetectable' and is a key goal of anti-HIV treatment, though it does not mean that the virus has been eradicated.6

CD4 Count

CD4 count refers to the measurement of the number of CD4 cells in a cubic millimetre of blood.7 The British HIV Association (BHIVA) recommends treatment should start before an individual's CD4 count falls below 200 cells/mm3.8 The CD4 count of a person who is not infected with HIV is usually between 500-1200.7

About Merck Sharp & Dohme Limited

Merck Sharp & Dohme Limited (MSD) is the UK subsidiary of Merck & Co., Inc., of Whitehouse Station, New Jersey, USA, a leading research-based pharmaceutical company that discovers, develops, manufactures and markets a wide range of innovative pharmaceutical products to improve human health.

References

1. Cooper DA, Gatell J, Rockstroh J, et al. 48-week results from BENCHMARK-1, a Phase III study of raltegravir (RAL) in patients failing antiretroviral therapy (ART) with triple-class resistant HIV_1 (poster abstract). Presented at the 15th Conference on Retroviruses and Opportunistic Infections; February 3, 2008; Boston, MA.

2. Steigbigel R, Kumar P, Eron J, et al.48-week results from BENCHMRK-2, a Phase III study of raltegravir (RAL) in patients failing antiretroviral therapy (ART) with triple-class resistant HIV (poster abstract). Presented at the 15th Conference on Retroviruses and Opportunistic Infections; February 3, 2008; Boston, MA.

3. http://www..tht.org.uk/mediacentre/pressreleases/2008/april/april10.htm (accessed on 23 April 2008)

4. HIV Scotland. http://www.hivscotland.com/stats.htm (accessed on 23 April 2008)

5. Health Protection Scotland. http://www.hps.scot.nhs.uk (accessed on 23 April 2008)

6. Aidsmap. 2007. Viral Load [online]. Available at: http://www.aidsmap.com/en/docs/040DB2E5-EA62-4C06- AC6A-8990528CA1FB.asp [accessed 4 February 2008]

7. Dawson, R. 2007. Viral load & CD4. 7th ed. London: NAM.

8. British HIV Association. 2006. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006) [online]. Available at: http://www.bhiva.org/files/file1001303.pdf [accessed 4 February 2008].

Scottish Medicines Consortium