Welcome to your weekly digest of approaching regulatory and clinical readouts. Bictegravir/F/TAF, Gilead’s new single-pill triplet for HIV, is due before the US regulators on February 12, and is expected to become a big seller; but it will have to keep Glaxo’s dolutegravir-containing regimens at bay.
Apellis Pharmaceuticals will report 18-month data from its trial of APL-2, a complement inhibitor, in geographic atrophy. The monthly injections were shown to work at one year, but no further drug was administered during the extra six months, so the new data will determine whether a sustained response is present.
Bictegravir/F/TAF is expected to become Gilead’s biggest growth driver, with forecast sales of $5.1bn in 2022, according to EvaluatePharma sellside consensus. The project could be the top launch of this year (Blockbuster approvals line up for biopharma in 2018, January 16, 2018).
It combines bictegravir, emtricitabine and tenofovir alafenamide, and Gilead expects to launch it in the US in the first quarter, and in Europe at the mid-year.
The aim is to take market share from Glaxo’s dolutegravir-containing regimens. Bictegravir/F/TAF will just overtake Glaxo’s marketed dolutegravir-containing triplet Triumeq by 2022, according to consensus. In phase III bictegravir/F/TAF showed non-inferiority – but not superiority – to dolutegravir-containing regimens, including Triumeq. It also showed non-inferiority in two switching studies.
Glaxo hopes to have an ace up its sleeve in the form of Juluca, its recently approved HIV doublet. The theory is that doublets could cut the chronic toxicity associated with traditional three-drug regimens, but questions linger over the risk of resistance with doublets, so the launch trajectory of Juluca will be watched closely (Glaxo scores HIV double, but bigger tests loom, November 23, 2017).
2022 consensus for Juluca sits at $546m, perhaps reflecting these concerns. Furthermore, Juluca contains rilpivirine, the active ingredient in Johnson & Johnson’s Edurant, so Glaxo will have to share its spoils.
|Top five HIV products by 2022|
|Annual HIV sales ($bn)|
|Bictegravir/F/TAF||Bictegravir-based triple||Gilead Sciences||-||5.1||Filed|
|Genvoya||Elvitegravir-based quad||Gilead Sciences||3.6||2.9||Marketed|
|Odefsey||Emtricitabine; rilpivirine hydrochloride; tenofovir alafenamide||Gilead Sciences||1.1||2.0||Marketed|
Apellis Pharmaceuticals’ IPO raised $150m towards the end of 2017, and the shares have since risen 23%. Its APL-2 intravitreal is a complement C3 inhibitor being tested in geographic atrophy (GA), a severe form of dry age-related macular degeneration (AMD), for which no specific treatments exist.
In February the company is to report 18-month data from its 246-patient phase II Filly trial, which will determine whether APL-2 shows a sustained response.
After a year’s treatment there was a 29% reduction in the rate of GA lesion growth in patients given monthly injections of APL-2 versus sham control, and this had a p value of 0.008. A second group was given treatment every other month and showed a 20% reduction, with a p value of 0.067. The company have stated that the pre-specified level of significance in this trial was 0.1.
One concern was the number of patients whose GA converted to wet AMD – which is more severe and can lead to rapid degeneration in central vision – in the study eye. In the monthly APL-2 group 18% developed wet AMD versus 8% in patients given treatment every other month and 1% in the sham group. Patients were given anti-VEGF therapy to treat the wet AMD.
Apellis did not screen out patients who had a history of choroidal neovascularisation in the non-study eye. As this condition involves abnormal growth of new blood vessels, a major feature of wet AMD, this could have driven the conversion rates. This will no doubt be closely watched when the 18-month safety data are reported, as well as in phase III.
The phase III programme is expected to start in the second half of the year and consists of two identical 600-patient double-masked, sham-controlled studies. The primary measure is the same as in phase II, change in lesion size at one year. Patients who develop wet AMD will continue treatment with APL-2 along with anti-VEGF therapy.
Apellis has few competitors targeting the complement pathway in GA – even fewer since Roche’s antibody lampalizumab, which targeted complement factor D, failed in phase III last year. 2022 sales expectations for lampalizumab once hit over $2bn, according to EvaluatePharma's forecasts archived.
Some competitors still exist. Novartis has an antibody, tesidolumab, which hits another part of the alternative complement pathway – it is in phase II trials in combination with CLG561. And Ophthotech’s Zimura is expected to yield phase IIb data in the second half of 2019.
|Tesidolumab + CLG561||Novartis||-||NCT02515942|