Virus World

"Having this treatment available for some patients provides an alternative for managing this chronic condition," said FDA's John Farley.  In a move that could transform HIV treatment, the Food and Drug Administration has approved a monthly injectable medication, a regimen designed to rival pills that must be taken daily. The newly approved medicine, which is called Cabenuva, represents a significant advance in treating what continues to be a highly infectious disease. In 2018, for instance, there were approximately 36,400 newly infected patients living with HIV in the U.S., according to the Centers for Disease Control and Prevention. About 1.7 million people worldwide became newly infected in 2019, according to UNAIDS. Although several medicines exist for treating HIV, ViiV Healthcare is banking on the improved convenience of getting a monthly shot, even if it must be administered by a health care provider. The company, which is largely controlled by GlaxoSmithKline (GSK), gathered data showing nine of 10 patients in pivotal studies claimed to prefer the shot over taking pills each day.

“This approval will allow some patients the option of receiving once-monthly injections in lieu of a daily oral treatment regimen,” said John Farley, who heads the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, in a statement. “Having this treatment available for some patients provides an alternative for managing this chronic condition.” Two clinical studies of more than 1,100 patients from 16 countries found that Cabenuva was as effective in suppressing the virus as the daily, oral, three-drug regimens that were taken by patients throughout the 48-week study period. However, patients must first take an oral version of the injectable medicine and another pill for the first month before pivoting to monthly shots, according to the FDA.  The cost, however, is steep — the list, or wholesale, price is $3,960 a month, or more than $47,500 a year. The list price for the one-time initiation dose is $5,490. However, a ViiV spokeswoman explained that a 30-day oral “lead-in,” which is required as part of the approval, will be made available at no charge to patients. She also maintained the list price for the monthly shot is “within the range” of HIV treatment pills on the market today. There is also considerable competition from Gilead Sciences (GILD), which markets several HIV medicines. During 2019, its HIV treatment franchise generated $17.2 billion in revenue, a 12.5% year-over-year increase, and grabbed more than 80% of the market for patients starting HIV therapy, according to Cowen analyst Phil Nadeau. He expects HIV medication sales to hit $24.4 billion in 2025, but points to HIV prevention pills as big drivers of that increase. ViiV, meanwhile, is developing an every-other-month injectable in hopes of capturing a more substantial market share.

Last November, an interim analysis found cabotegravir – a component of Cabenuva – was 89% more effective in preventing infection among women than Truvada, a Gilead pill that must be taken daily and is the current standard of care. And a separate analysis released in July showed the every-other-month shot protected uninfected people by 66% more compared with Truvada in at-risk men and transgender women who have sex with men. “We see Cabenuva as the beginning of long-acting treatment for HIV,” said Kimberly Smith, who heads global research and medical strategy at ViiV, who expects to seek FDA approval for this version of the shot in coming weeks. “We’re opening the door with Cabenuva and will only create more hunger for other long-acting therapies. It really becomes a sort of anchor.” The approval, by the way, comes more than a year after ViiV hoped to win approval for the treatment. In late 2019, the FDA issued a so-called complete response letter and explained approval could not be granted at the time due to issues with chemistry, manufacturing and controls, which are used to determine safety, effectiveness and quality.

FDA News Release (Jan 21, 2021):

https://www.fda.gov/news-events/press-announcements/fda-approves-first-extended-release-injectable-drug-regimen-adults-living-hiv#

ViiV Healthcare announced that it has received a complete response letter (CRL) from the FDA, rejecting its marketing application for its long-acting, monthly injectable therapy for HIV. The combination treatment was touted by ViiV as a next generation HIV therapy, due to the fact that it could free people with the virus from taking daily oral pills. The monthly injection  is a combination of ViiV’s integrase inhibitor cabotegravir and Johnson & Johnson’s non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine.

ViiV – which is majority owned by GlaxoSmithKline – said that it “will work closely with the FDA to determine the appropriate next steps for this new drug application”. In the CRL, the FDA cited concerns regarding the treatment’s chemistry manufacturing and controls process, but there was no issues surrounding the safety of the product. This is a blow to ViiV, which has been vying for market share from Gilead. Both companies make billions of dollars each year from selling daily oral drugs for HIV, so this monthly injectable could have made a significant dent in Gilead’s sales. In previous trials testing the long-acting treatment, ViiV’s injectable was as effective as a standard three-drug oral regime at suppressing levels of HIV. Two trials, named ATLAS and FLAIR, formed the basis of the regulatory filings for the regimen. ATLAS involved patients who had been previously treated with long-acting antiretroviral therapy (ART), and showed that the combination injection matched standard therapy on viral suppression rates. Three patients treated with ViiV’s injectable (1%) demonstrated a failure to suppress HIV, while there were four cases on the oral therapy. FLAIR recruited newly-diagnosed patients and along with data showing non-inferiority to oral treatment, revealed a similar 1% rate of treatment failure, caused by the emergence of treatment resistance strains.

ViiV’s rival Gilead was the first company to bring a single-tablet triple therapy – Biktarvy – to market, and the former has been desperately pushing its own two-drug oral therapies through the pipeline to try and claim more market share. Gilead’s Biktarvy has grown quickly since its launch last year, and will most likely hit a $1bn-plus annual sales rate. According to GlobalData, the overall value of the HIV market is not expected to change dramatically in upcoming years, but there will be a predicted shift towards increased use of simpler, single-tablet regimens as the big-selling products change.

(Reuters) - GlaxoSmithKline Plc said an injection of its cabotegravir drug given every two months, in combination with Johnson & Johnson’s rilpivirine, was recommended for approval to treat HIV infections by a panel of the European health regulator. The treatment is a long-acting regimen, which can reduce the number of doses required to 12 or six per year instead of a daily intake of pills. If approved, it would be the first complete long-acting HIV regimen requiring dosing just once in two months (in the EU region), GSK said. The combination as an injection is already approved in Canada and is currently under review in the United States. Shares of GSK were trading up 2.5% at 1410.4p, while J&J shares were marginally up during premarket trading. Gilead’s Truvada daily oral pill is currently the standard of care for preventing HIV, but GSK hopes to challenge its dominance by making shorter, long-lasting regimens and less toxic alternatives through its ViiV Healthcare unit.

The positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency comes months after GSK said cabotegravir was found to be 66% more effective in preventing HIV infections than Truvada. Some 75 million people worldwide have been infected with HIV and about 32 million people have died since it began in the 1980s. While final approvals are up to the European Commission, it generally follows the CHMP’s recommendation and endorses them within a couple of months.

GSK public announcement (Oct. 16, 2020):

https://www.gsk.com/en-gb/media/press-releases/viiv-healthcare-receives-positive-chmp-opinion-for-long-acting-regimen-for-the-treatment-of-hiv/