New Treatment Opportunity: Valganciclovir Arax Bozadjian, PharmD International AIDS Conference Kuala Lumpur, Malaysia June 2013

Outline Current Treatment Options Advantages and Disadvantages of existing forms of treatment Price Analysis Assumptions Price Analysis-Oral Valganciclovir Price Analysis-Intraocular Ganciclovir Barriers to scaling up treatment of CMV retinitis with oral therapy Overcoming barriers to enable access to oral therapy

Current Treatment Options Ganciclovir Systemic Injection Intravitreal Injection Intraocular Injection Intraocular Implant Valganciclovir Oral tablet MSF focus is on intraocular and oral therapy

Advantages and Disadvantages Systemic Oral therapy -Easy to administer -Systemic efficacy -No training of staff -Benefit contra-lateral eye -IDSA/CDC/NIH recommended -Systemic side effects (pancytopenia, hypertension, diarrhea/nausea/vomiting) -Price Injectable (IV) therapy -Requires an IV line (hospitalization) -Trained staff –Systemic side effects (pancytopenia, renal dysfunction and GI side effects) Intra-ocular (IO) therapy -Efficacious -Ideal option for treatment of immediate eye-sight threatening lesions -Trained staff to administer -Discomfort for both patient and provider -Higher level of risk

Price Analysis Assumptions For the oral therapy we used two scenarios for the time frames: Induction phase: 3 weeks (Dose: 2 tablets twice daily) Maintenance phase: 9 weeks and 24 weeks (Dose: 2 tablets daily) For the intraocular injection we used the following time frames: Induction phase: 6 weeks (Dose: 0.05ml or 2.5 mg daily) Maintenance phase: 22 weeks (Dose: 0.05ml or 2.5 mg daily) The sources of our pricing is procurement reported prices, as well as private market prices -IDSA guidelines stated above Ophthalmol Clin North Am. 2002 Dec;15(4):529-36, viii. Cytomegalovirus retinitis in the era of combined highly active antiretroviral therapy. See RF, Rao NA. Ophthalmologe. 2000 Aug;97(8):574-6. [Stopping secondary prevention in AIDS patients with inactive CMV retinitis treated with HAART (highly active antiretroviral therapy)]. Best J, Althaus C, Kersten A, Theisen A, Gantke B. Ocul Immunol Inflamm. 1999 Dec;7(3-4):231-5. CMV retinitis in the era of HAART. Cassoux N, Bodaghi B, Katlama C, LeHoang P. Maintenance phase lasts until immune reconstitution is demonstrated, as defined by at least CD4 > 100, or assumed based on the duration of ART. CDC,IDSA Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected adults and adolescents 2009

Price analysis-Oral Valganciclovir The dosing for oral Valganciclovir 450 mg for the treatment of CMV retinitis is as follows: Induction Phase: 3 weeks = 84 tablets Maintenance Phase Scenario 1: 9 weeks = 126 tablets Maintenance Phase Scenario 2: 24 weeks = 336 tablets Total Number of tablets = 210 (Scenario 1) or 420 (Scenario 2)

Price analysis-Oral Valganciclovir Offer Price per tablet in USD 12 weeks Treatment regimen cost (USD/pp) 27 weeks Treatment regimen cost (USD/pp) Roche’s Valcyte® price from a procurement agency based in Europe (2012) 10.50 2,206 4,412 Roche’s Valcyte® price in Indian domestic market (2012) 12.03 2,527 5,053 Cipla’s generic Valganciclovir in Indian domestic market (2012) 3.53 741 1,482

Price analysis-Intraocular Ganciclovir Induction (6 weeks) Maintenance (22 weeks) Total treatment (28 weeks) 1/5th patients (20 patients) 4/5th patients (80 patients) Total 100 patients 20 pts x 6 injections x 2.5 mg per dose = 300 mg 80 pts x 8 injections x 2.5 mg per dose = 1600 mg Total = 1600 mg + 300 mg = 1900 mg Assuming 100 patients are in our clinic, and the single dose is 0.05 ml (2.5 mg) The cost of 1 vial of Ganciclovir from a procurement agent in Europe is $ 35 USD The need based upon above scenario is approximately 4 vials (1900mg ÷ 500 mg) Approximately 4 vials are needed to treat 100 patients at our clinic 4 vials x 35 USD per vial = 140 USD to treat 100 patients In this calculation, we did not take into consideration the cost of training the staff to administer the intraocular injections, the additional medical devices that are needed, such as syringes, needles and gloves; and the cost of the sterile water to reconstitute the Ganciclovir vial ; and the cost of the drops to anesthetize the eyes. One vial of 500mg Ganciclovir is diluted with 10ml sterile preservative free water, giving a solution of 50 mg/ml. The injection dose is 0.05ml of Ganciclovir solution which is equal to 2.5mg dose of Ganciclovir. However, 0.1ml (equal to 5 mg) is drawn into the syringe for each injection to help ensure there are no bubbles during the administration. The remaining 0.05 ml is discarded. The vial is kept for 1 month after being opened and reconstituted.

Barriers to Scaling Up Treatment of CMV retinitis with Oral Therapy Currently, there is insufficient demand for Valganciclovir due to: Patients under-diagnosed for CMV retinitis Lack of normative clinical guidance on CMV retinitis (for screening and treatment) Lack of donor interest in opportunistic infections Current high costs of oral therapy as compared to the intraocular injection No demand, hence no supply - Countries, advocates and donors needs to focus on addressing these barriers to meet the needs of PLWHA and save their sight and lives -A vicious cycle (supply-demand)

Overcoming Barriers to enable Access to Oral Therapy Global Level: WHO to rapidly issue evidence-based treatment guidelines Enabling generic competition for additional quality-assured and affordable sources of Valganciclovir Negotiation with the originator company to reduce the price of Valganciclovir Donors to include diagnosis and treatment of CMVr as a component of basic HIV package of care

Questions and Comments? Arax.Bozadjian@geneva.msf.org Thank You Questions and Comments? Arax.Bozadjian@geneva.msf.org