Feb. 18, 2010; 1:15 a.m. Pacific Time
For those of you who last used the word "quad" to describe that dorm you went to in college where you got totally wasted, it's time to update your vocabulary.
Calvin Cohen, M.D., unveiled new 24-week data on Wednesday from an intriguing pair of phase 2 trials. One of them pits the current U.S. standard of care in initial antiretroviral therapy, efavirenz/tenofovir/emtricitabine (Atripla), against a fixed-dose combination drug in development known as the "quad" tablet, which is comprised of tenofovir/emtricitabine (Truvada), the investigational integrase inhibitor elvitegravir and a novel booster drug in development, GS 9350. The other looks at GS 9350 itself -- specifically, how well it holds up against ritonavir (Norvir) as a pharmacokinetic booster when either is administered alongside atazanavir (Reyataz) and tenofovir/emtricitabine.
We'll follow up with more data soon, but in a nutshell, there were two key takeaways from these studies:
Much has been made, in parsing the results of earlier studies involving GS 9350, about the potential for the drug to negatively impact serum creatinine levels, which raised fears about the potential for renal issues with the drug. In response to those concerns, Dr. Cohen devoted four of his 18 slides to a discussion of GS 9350's impact on creatinine, all of which appear to support his conclusion that the drug is no worse on the kidneys than cimetidine, an over-the-counter acid blocker known by the brand name Tagamet.
Cohen's central assertion was that the modest impact of GS 9350 on serum creatinine (which increased 0.14 mg/dL among quad patients, versus an increase of 0.04 mg/dL among efavirenz/tenofovir/emtricitabine patients -- and notably, the increase among quad patients was not cumulative over time, but rather remained stable through 24 weeks), coupled with what appeared to be no real impact on the actual glomerular filtration rate, indicated that GS 9350's impact on creatinine was an issue of tubular secretion, not drug-related glomerular filtration. Presumably, a phase 3 trial that enrolls many more patients (only 71 were involved in the quad phase 2 study) will flesh this issue out even further if needed.
Based on these results, both the quad pill and GS 9350 will sail through to phase 3 trials. GS 9350 has also been given a graduation present -- a generic name, and a sufficiently hard-to-pronounce one at that: cobicistat (that's koe-bih-SIH-stat).
It's difficult to decide what the bigger story is here. It is certainly exciting and encouraging that the quad pill could potentially provide a viable alternative to efavirenz/tenofovir/emtricitabine for the not-insignificant number of people who currently take the drug because it's convenient but then have to deal with CNS issues that damage their quality of life. But there is also an undeniable allure to the potential for cobicistat to finally break ritonavir's rock-solid hold on the antiretroviral booster market. Judging by the criticism ritonavir has received over its toxicity profile and price level (not to mention the F that ritonavir distributor Abbott Laboratories got last year from the AIDS Treatment Activists Coalition), it appears a large cross-section of the HIV/AIDS clinical and advocacy communities likely agree with that sentiment.