Lenacapavir capsid inhibitor (GS-6207) - CAPELLA trial

[Jim Allen]

An update and good results from the Lenacapavir Capella trial.

POZ.com full writeup https://www.poz.com/article/lenacapavir-shows-promise-longacting-hiv-treatment-prevention

In Short:

Lenacapavir, the first HIV capsid inhibitor, led to viral load reductions in 88% of people who had received several prior antiretroviral medications and had multidrug-resistant virus, according to Gilead Sciences.

Researchers are also evaluating lenacapavir as a twice-yearly injectable for HIV pre-exposure prophylaxis (PrEP), which could expand the armamentarium of long-acting prevention options.

The Phase II/III CAPELLA trial included 36 adults with resistance to multiple antiretroviral drug classes who had a detectable viral load on their current treatment regimen. About two thirds of those who received lenacapavir had advanced immune suppression with a CD4 count below 200.

The participants were randomly assigned to add either lenacapavir or a placebo given by subcutaneous injection to their failing regimens for 14 days—that is, lenacapavir was essentially functioning as monotherapy. At that point, all participants were offered open-label lenacapavir plus an optimized background regimen designed to work as well as possible based on resistance testing. They will receive lenacapavir injections every six months as maintenance therapy.

At the end of the two-week period, 88% of those assigned to lenacapavir experienced at least a half-log reduction in viral load, compared with just 17% in the placebo group. Despite the small numbers, the difference was highly statistically significant, meaning it was probably not attributable to chance. What’s more, people in the lenacapavir group saw a significantly greater average change in viral load compared with the placebo group (-1.93 versus -0.29 log).

A previous posting on phase 1 safety testing: Early Trial of Gilead’s HIV Capsid Inhibitor Supports 3-Month https://forums.poz.com/index.php?topic=71933

[MitchMiller]

FOSTER CITY, Calif.Gilead Sciences, Inc. (Nasdaq: GILD) today announced new one-year results from the ongoing Phase 2/3 CAPELLA trial evaluating lenacapavir, the company’s investigational, long-acting HIV-1 capsid inhibitor, in heavily treatment-experienced people living with multi-drug resistant HIV. The findings demonstrated that lenacapavir, administered subcutaneously every six months in combination with other antiretrovirals, achieved high rates of virologic suppression and clinically meaningful increases in CD4 counts in people living with HIV whose virus was no longer effectively responding to their current therapy.

https://www.stonkmoon.com/news/GILD/7197c1205c666e64df304145dcd98cdc

[Da2020]

I read they also fid some other trails on treatment naive patients with other drugs and found the results to be good. Hoping they can find something to use in combination to lencapavir, so that we can get to twice a year dosing instead of daily pills

[Jim Allen]

May 12th 2022 - In full: I-base: https://i-base.info/htb/42883
Lenacapavir in MDR HIV: phase 3 results of CAPELLA study published

In Brief:

Notably, lenacapavir is given by subcutaneous injection every six months, but it still needs to be used in combination with other active drugs. This is likely to include oral dosing, until other long-acting options become available.

Without this support, resistance to lenacapavir can develop easily if viral load remains unsuppressed or if adherence to other drugs in the combination is not high Viral failure was reported in 8/72 participants in CAPELLA, generally early, and with 4/8 linked to low adherence.

Lenacapavir has so far been associated with few side effects, other than injection site reactions which are generally mild; only two participants reported grade 3 events, both of which resolved. None of the serious events reported in seven participants were judged related to lenacapavir.

[Jim Allen]

The Phase III CAPELLA + CALIBRATE II trial & FDA Lifts Clinical Hold on Long-Acting Lenacapavir

https://www.poz.com/article/fda-lifts-clinical-hold-longacting-lenacapavir

In Brief:

Clinical Hold

In late December 2021, Gilead announced that the FDA had put a clinical hold on trials of lenacapavir due to concerns about the type of glass vial used for the injectable formulation, which resulted in tiny glass particles in the medication.

This week, Gilead announced that the FDA has lifted the clinical hold on the company’s Investigational New Drug application, allowing trials of injectable lenacapavir for treatment and PrEP to continue.

[Da2020]

Hopefully, it gets approved soon and I am eager to switch to  twice a year injections opposed to daily pills.

[Jim Allen]

Hopefully, it gets approved soon and I am eager to switch to  twice a year injections opposed to daily pills.

From what I read and the results, Initial approve and that's a "if" that happens I think will be in combination of daily oral drugs for viral suppression.

If it was just 6 monthly injection and done, then I would also be interested as well but we're not there yet

[Loa111]

From what I read and the results, Initial approve and that's a "if" that happens I think will be in combination of daily oral drugs for viral suppression.

So if with the 6 month injection and if daily oral drugs are still required anyway, is the benefit that one is taking less drugs on a daily basis?

[Jim Allen]

Well... The way I look at it is if it works then it's a first and, should there be any additional 6 monthly treatments in the future then prehaps a combination of those could truly provide an alternative to daily pills.

The current benefits that CAPELLA trial phase 3 is looking into is suppressing the VL in those with HIV that has become multidrug-resistant. These injections and an optimized daily meds will hopefully suppress the virus and the results so far are promising.

The Phase II CALIBRATE trial, is looking into 6 monthly injections with the daily combinations for those without resistance.

lenacapavir +  daily alafenamide/emtricitabine
Or;
lenacapavir +  daily bictegravir
Or;
lenacapavir +  daily bictegravir/TAF/emtricitabine
Or;
lenacapavir +  daily TAF

I would be more interested if it was in combination with DTG or 3TC but even then it's not for me, However, hopefully it will provide other people with more treatment options to choose from.

(Sorry for any spelling issues, walking around Kilkenny today and only have this tiny phone with me)

[Loa111]

Interesting...I'm on a 2 pill combo, so I would be open to the idea if this worked, of just taking of one my daily pills if the 6 monthly injection took care of the rest.

Thanks for the insight Jim & enjoy your walk around Kilkenny.

[Jim Allen]

Thanks.

[Jim Allen]

https://www.poz.com/article/europe-approves-twiceyearly-sunlenca-people-resistant-hiv

Europe Approves Twice-Yearly Sunlenca for People With Resistant HIV

On August 22, the European Commission was the first to approve long-acting Sunlenca (lenacapavir) as a new option for heavily treatment-experienced people with multidrug-resistant HIV who cannot otherwise construct an antiretroviral regimen that fully suppresses their virus. The authorization covers injectable Sunlenca and a tablet formulation used for an initial oral loading period.

“Lenacapavir helps to fill a critical unmet need for people with complex prior treatment histories and offers physicians a long-awaited twice-yearly option for these patients who are at greater risk of progressing to AIDS,” Jean-Michel Molina, MD, of Université Paris Cité, said in a Gilead Sciences press release. “Lenacapavir provides an innovative long-acting HIV therapy option with the potential to transform the clinical landscape.”

[Jim Allen]

https://www.poz.com/article/lenacapavir-shows-continued-promise-people-drugresistant-hiv

In Brief:

CAPELLA study

The study enrolled people who were currently on antiretroviral therapy but unable to maintain an undetectable viral load. Nearly two thirds had advanced immune suppression with a CD4 count below 200. In one cohort, 36 participants were randomly assigned to add either oral lenacapavir or placebo pills to their failing regimen for 14 days, then everyone was offered lenacapavir injections every six months plus an optimized background regimen. Another 36 people in a nonrandomized cohort started lenacapavir plus an optimized background regimen from the outset.

Lenacapavir continued to work well at 52 weeks for both people younger than 50 years (89% with HIV RNA below 50) and for those ages 50 or older (82%). Response rates were 77% for men, 100% for women, 75% for Black people and 90% for people of other racial groups.

People with a CD4 count below 200 at baseline—those in greatest need of effective treatment—had a response rate of 78%, while all nine people with higher CD4 counts achieved viral suppression. People who started lenacapavir with a high viral load above 100,000 copies had a response rate of 71%, which rise to 86% for those with a lower baseline viral load.

“In people with HIV who were highly treatment experienced with limited treatment options due to [multidrug-resistant HIV], lenacapavir in combination with an optimized background regimen les to high rates of virologic suppression,” the researchers concluded. “No clinically relevant differences were seen in efficacy among subgroups who were considered more difficult to treat.”

[Jim Allen]

FDA Approves Twice-Yearly Sunlenca for People With Drug-Resistant HIV
https://www.poz.com/article/fda-approves-twiceyearly-sunlenca-people-drugresistant-hiv

On December 22, the Food and Drug Administration (FDA) approved Sunlenca (lenacapavir) as a new option for treatment-experienced people with multidrug-resistant HIV who are unable to maintain viral suppression on their current antiretroviral regimen. Sunlenca is also approved in the United Kingdom, Europe and Canada. The approval does not include first-time HIV treatment or pre-exposure prophylaxis (PrEP), though Sunlenca is being studied for these indications.

[Da2020]

Now if they would make that thing work for everyone

[Jim Allen]

What daily pills + twice yearly injections to somewhat suppress the viral load? No thanks.

I get what you mean, though. However a long road to go before there is any drug combination, if it ever happens, that can, without daily meds, provide viral suppression purely from a once-per-six monthly injection. 

[Da2020]

I meant as a stand alone treatment without the daily pills. I know they were working on it with Merck and mercks drug had issues with reduction in CD4 counts. I don’t want a pill plus the twice a year injection either 

[Jim Allen]

I meant as a stand alone treatment without the daily pills. I know they were working on it with Merck and mercks drug had issues with reduction in CD4 counts. I don’t want a pill plus the twice a year injection either 

That reminded me to update that thread, thanks. https://forums.poz.com/index.php?topic=75770
It was on hold, now continuing at a lower dose, and they dropped the idea of using it for PrEP. However, even if it works, its nowhere near 6 monthly injections. 

[Jim Allen]

https://www.poz.com/article/twiceyearly-sunlenca-works-initial-hiv-treatment

The new injectable antiretroviral keeps HIV under control, but it still needs an equally long-acting partner.

Sunlenca (lenacapavir), a long-acting injectable medication recently approved for treatment-experienced people with multidrug-resistant HIV, also works well for people starting antiretroviral therapy for the first time, according to a recent report in The Lancet HIV.

Results from the CALIBRATE trial showed that around 90% of study participants who used Sunlenca—either as daily pills or injections every six months—in combination with other antiretrovirals achieved an undetectable viral load.