- Lenacapavir (Sunlenca) is the first capsid inhibitor approved for HIV treatment
- Lenacapavir works in a way that is different from other HIV medications
- After initial oral dosing, lenacapavir injections are given every six months
Effective HIV treatment first became available in the mid-1990s. At that time, HIV drug regimens involved having to take a fistful of pills two or three times daily. These early regimens usually had food and water restrictions, as well as many side effects.
Over the past 20 years, pharmaceutical companies have combined entire treatment regimens (sometimes consisting of two, three or four medications) inside one pill. Thus, for many people, HIV treatment now consists of taking just one pill once a day. Also, treatments have become safer and more active against HIV.
The era of long-acting treatment begins
In 2020, Health Canada approved the first long-acting regimen for people with HIV—a combination of the drugs cabotegravir and rilpivirine (sold as Cabenuva). These drugs can initially be taken in pill form for a few weeks and then administered by a healthcare provider as two injections into the buttocks once a month for a couple of months. After this time, patients and their doctors can decide whether subsequent injections should be given monthly or every two months.
Lenacapavir – the first capsid inhibitor
In November 2022, Health Canada approved a new drug for use in HIV treatment—lenacapavir (Sunlenca), developed by Gilead Sciences. Lenacapavir works in a different way from previously approved HIV treatments. By interfering with an HIV protein called the capsid, lenacapavir, when used in combination with other HIV drugs, can help suppress the production of new copies of HIV.
Lenacapavir will be available in two formulations—a pill for oral use and a liquid formulation for injection just under the skin (subcutaneous injection). When initiating treatment with lenacapavir, the pill formulation is taken on days one, two and eight, after which no further oral doses are needed. On day 15 of the initiation period, a healthcare provider injects two doses of lenacapavir into the belly. Subsequent injections are then needed every six months to maintain effective levels of lenacapavir in the blood.
For now (and for the foreseeable future), lenacapavir needs to be taken with oral formulations of other HIV treatments, as this drug on its own is not sufficient to treat HIV. However, Gilead Sciences is conducting research to find a new drug that can be taken with lenacapavir that has an equally long dosing interval. It is thus plausible that one day there will be a combination of drugs for HIV treatment that only has to be injected every six months.
Lenacapavir pills can be taken with or without food.
Who is lenacapavir meant for?
Lenacapavir is approved for use by adults who have HIV-1 that is resistant to many other treatments and whose current regimen is failing due to drug resistance or intolerance. In lab experiments, lenacapavir is 15- to 25-fold less active against HIV-2 than HIV-1.
Effectiveness in heavily treatment-experienced people
In a partially randomized, placebo-controlled study called Capella, researchers assessed the impact of lenacapavir in 72 people who had HIV that was resistant to multiple treatments. After 52 weeks, 83% of participants had a viral load that was undetectable. The greater the number of drugs that were fully active against HIV in a person’s regimen, the greater their chance of achieving an undetectable viral load.
Safety
Lenacapavir has been studied in clinical trials with at least 229 people with HIV. Side effects reported in those studies included the following:
- nausea
- diarrhea
- headache
These side effects were generally mild or moderate and temporary.
Skin reactions at the point of injection are to be expected with all medicines that require injection. Such reactions—including redness, swelling and itching—were common with lenacapavir but most were mild and temporary.
Special circumstances and populations
Pregnancy
In lab experiments, lenacapavir did not cause birth defects in rabbits or rats. It also did not cause developmental problems in infant rats. However, animal experiments do not always mirror what occurs in humans. Lenacapavir has not been tested in pregnant people. Gilead advises that lenacapavir “should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.”
Kidney health
Gilead advises that no dose adjustment of lenacapavir is needed in people with “mild, moderate or severe renal impairment.”
Liver health
Gilead also advises that “no dose adjustment is required in patients with mild to moderate hepatic impairment.” Gilead graded this range of hepatic impairment as Child-Pugh A or B. Lenacapavir has not been studied in people with severe hepatic impairment (graded as Child-Pugh C).
Lenacapavir has not been studied in people who are co-infected with HIV and active hepatitis C virus (HCV). The drug also has not been studied in people with HIV and untreated hepatitis B virus (HBV).
Older people
Lenacapavir has not been studied in large numbers of people aged 65 and older.
Drug interactions
Many medicines interact with other medicines by either raising or lowering the level of one of the medicines in the blood. When levels of a drug are raised, it can lead to new side effects or it can intensify existing side effects. When levels of a drug are reduced below the normal range, it can lead to treatment failure. In the case of HIV medicines, less-than-ideal levels of a drug can lead to the development of HIV that is resistant to one or more drugs. Such resistance can limit future treatment options.
Gilead advises that people taking lenacapavir should not take the following drugs:
- antiseizure drugs – carbamazepine, phenytoin
- antibiotics – rifampin, rifapentine
- herbs – St. John’s wort (and its extracts)
There are other drug interactions that can occur when taking lenacapavir, so discussion with a pharmacist prior to starting a new medicine or changing a drug regimen is important.
Access
After Health Canada licenses a treatment, physicians can prescribe it, but initially patients must pay for it themselves unless they have a private insurance plan that covers the cost. It usually takes between three and six months before private insurance plans list a drug on their formularies.
If left untreated, HIV infection leads to catastrophic disease that can affect one’s ability to work. HIV treatment is expensive. In Canada, provincial and territorial ministries of health heavily subsidize the cost of anti-HIV medications. Each ministry has a listing of the drugs for which it is prepared to pay. These listings are called formularies.
In the months ahead, Gilead and provincial and territorial ministries of health will be negotiating the price of lenacapavir. This process may not be completed until sometime in 2024. Check with a pharmacist to find out when lenacapavir is listed on your region’s formulary.
In Canada, lenacapavir should be ready for ordering by wholesalers and pharmacies in a few months. At publication time, Gilead has not made its price for lenacapavir publicly available.
A CATIE Fact sheet on lenacapavir is in development. Some information about clinical trials with lenacapavir is available in the Resource section below.
A note on prevention
Lenacapavir is being tested in clinical trials with thousands of HIV-negative people for its ability to reduce the risk of acquiring this virus. Complete results from those studies may not be available for at least a couple of years. If lenacapavir is found to be highly effective for prevention, Gilead will submit data from these trials to regulatory authorities for approval. Therefore, it may be several years before lenacapavir is approved for the prevention of HIV. After that, it will take additional time for lenacapavir to be listed on Canada’s provincial and territorial formularies for this use, depending on the price asked by the pharmaceutical company.
Resource
Lenacapavir and multidrug resistant HIV – TreatmentUpdate 246
—Sean R. Hosein
REFERENCES:
- Gilead Sciences Canada. Sunlenca: lenacapavir subcutaneous injection and lenacapavir tablets. Product Monograph. 1 November 2022.
- Margot NA, Naik V, VanderVeen L, et al. Resistance analyses in highly treatment-experienced people with HIV treated with the novel capsid HIV inhibitor lenacapavir. Journal of Infectious Diseases. 2022 Sep 9:jiac364.
- Cilento ME, Ong YT, Tedbury PR, et al. Drug interactions in lenacapavir-based long-acting antiviral combinations. Viruses. 2022 May 31;14(6):1202.
- Segal-Maurer S, DeJesus E, Stellbrink HJ, et al. Capsid inhibition with lenacapavir in multidrug-resistant HIV-1 infection. New England Journal of Medicine. 2022 May 12;386(19):1793-1803.
- Troyano-Hernáez P, Reinosa R, Holguín Á. HIV capsid protein genetic diversity across HIV-1 variants and impact on new capsid-inhibitor lenacapavir. Frontiers in Microbiology. 2022 Apr 12;13:854974.
- Margot N, Vanderveen L, Naik V, et al. Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study. Journal of Antimicrobial Chemotherapy. 2022 Mar 31;77(4):989-995.
- Dvory-Sobol H, Shaik N, Callebaut C, et al. Lenacapavir: a first-in-class HIV-1 capsid inhibitor. Current Opinion in HIV/AIDS. 2022 Jan 1;17(1):15-21.