Cabotegravir (S-1265744) is an integrase inhibitor similar to dolutegravir. When formulated as a long-acting drug using crystalline nanoparticle technology it is called GSK’744 LAP. When injected intramuscularly, ‘744 LAP it has a half-life of >1 month which makes it ideally suited for PrEP of HIV for high-risk patients who nowadays are candidates for Truvada (tenofovir/emtricitabine) prophylaxis. While the intracellular half-life of tenofovir (TFV) is several days, Truvada has to be taken once daily.
Fig. 1+2: Both drugs are structurally almost identical.
Compliance is a major issue in HIV therapy. Hence, cabotegravir, injected every 3 months, would greatly improve adherence and therefore reduce the risk of HIV transmission.
This is the rationale why HPTN (the HIV Prevention Trial Network) is actively supporting PrEP studies with long-acting agents like cabotegravir.
According to an announcement from Feb 18, 2015, HPTN has launched two new Phase 2 studies for long-acting prophylaxis drugs:
– Protocol 076: TMC278 LA / rilpivirine – the NNRTI from Janssen
– Protocol 077: GSK1265744 LAP / cabotegravir – developed by GSK and ViiV
Because of the public health importance of HIV and the non-profit nature of HPTN, these studies are supported by 3 major grants from NIH and NIAID:
– Award # UM1AI068619 (HPTN Leadership & Ops Center) – $ 20,980,154
– Award # UM1AI068617 (HPTN Statistical & Data Mgmt Center) – $ 9,184,867
– Award # UM1AI068613 (HPTN Laboratory Center) – $ 1,327,398
It is good to see such generous funding for worthwhile projects, and nothing said here should be construed to suggest that the goals of these trials are without merit or that NIH funding for HIV drug development is inappropriate. Just the opposite: Such studies are valuable, should be conducted, and executed expeditiously and with the best available expertise .
What seems unclear is the payback to the TAX PAYER: Who will reap the financial benefits when rilpivirine LA or cabotegravir LAP get approved? Does anyone want to guess? I venture to say that GSK and JNJ will be the sole beneficiaries, without consideration of the gracious support extended by NIH and NIAID. With $31 mio already granted for Phase 2 studies, I am curious about the price tag for the Phase 3 programs and how much more public funding will NIH provide.
It is good to see your tax dollars being used for anti-infective programs; we certainly need more MDR antibiotics, and these 2 long-acting HIV drugs will address an unmet need. However, both are me-too drugs and should not get federal funding without a decent ROI for the taxpayer as well. We are not dealing with VC companies in need of a government hand-out: NIH is giving money to the world’s biggest of Big Pharma companies.
Once on the market the price tag for either drug will make your eyes water – we are talking retail prices as high as for HCV drugs. However, these long-acting HIV drugs are not just given for 12 weeks but …for life!
Bottom line: This is the next great money-making opportunity for GSK and JNJ. It seems that – finally – HIV drugs beat oncology drugs as revenue generators for ‘Ethical Pharma’.
If taxpayer money is used in the development process, the price of the marketed drug should be considerably lower to the patient taxpayer who funded this research. My guess is that the monies from NIH / NIAIDS did not come with these strings attached.
