After a tough couple of months Novartis will be hoping for some relief, with a US approval decision approaching for one of its big pipeline hopes, Beovu. The wet age-related macular degeneration project is forecast to be among the biggest launches of 2019, but it will be going up against the might of Regeneron and Bayer’s Eylea.
A nod for Biogen’s Tecfidera follow-on Vumerity could give that group some rare good news, while Alexion also hopes to cement its franchise-extension efforts with a new use for Soliris’s successor, Ultomiris.
|Notable first-time US approval decisions due in October|
|Project||Company||PDUFA date||Product NPV ($m)|
|Scenesse||Clinuvel Pharmaceuticals||Oct 6||41|
|Beovu (brolucizumab)||Novartis||Oct 15 (estimate)||5,590|
|Xipere||Clearside Biomedical||Oct 19||208|
|Cosyntropin||Assertio Therapeutics||Oct 19||72|
|FMX-101||Foamix Pharmaceuticals||Oct 20||94|
|ET-202||Eton Pharmceuticals||Oct 21||-|
|Zimhi||Adamis Pharmaceuticals||Oct 31||23|
Approval of Beovu is expected. However, as the project has only shown non-inferiority to Eylea in the phase III Hawk and Harrier trials on best-corrected visual acuity, whether it can gain market share will be another matter.
Novartis, which used a priority review voucher to speed Beovu’s approval, hopes to differentiate its project on efficacy – the asset was linked with lower levels of disease activity versus Eylea – and convenience. Novartis’s project is injected into the eye every 12 weeks; while 12 and four-week dosing schedules for Eylea are approved, it is recommended every 8 weeks.
One way Novartis could make a splash is by undercutting Eylea’s price, but it is unlikely to do this from the start, Bernstein analysts believe. Instead, the company is taking the bold step of running various head-to-head studies of Beovu versus Eylea, with Merlin set to be the first to yield results next year.
|Head-to-head studies of Beovu vs Eylea|
|Trial name||Details||ID||Primary completion|
|Merlin||Wet AMD pts with prior anti-VEGF treatment||NCT03710564||Jun 2020|
|Raptor||DME secondary to branch retinal vein occlusion||NCT03802630||Sep 2021|
|Talon||Wet AMD, VEGF-naïve pts||NCT04005352||Aug 2022|
|Raven||DME secondary to central retinal vein occlusion||NCT03810313||Jan 2023|
|AMD: age-related macular degeneration; DME: diabetic macular oedema; VEGF: vascular endothelial growth factor. Source: EvaluatePharma, clinicaltrials.gov.|
Another big decision due in the fourth quarter will involve Biogen’s Tecfidera follow-on Vumerity, licensed from Alkermes, although this looks likely to come in November based on its acceptance date. Again, Biogen has a decent chance of approval, but the company will need to move patients onto the new drug before Tecfidera generics hit, which could happen as early as next year depending on the outcome of an inter partes review requested by Mylan.
Biogen recently reported that Vumerity was superior to Tecfidera in the head-to-head Evolve-MS-2 trial, but pricing and marketing will also be important to Vumerity’s success, should it get the nod.
Meanwhile, Foamix is on shakier ground with its acne candidate FMX101. After mixed results in its first two phase III trials, the company carried out a third – and much larger – pivotal study. This did show a statistically significant improvement over placebo on both co-primary endpoints, but there were questions about the numerical benefit and the potential market for FMX101.
And Clearside Biomedical looks likely to receive a complete response letter for its uveitis project after the FDA requested more data on stability, following a new manufacturing process being put into place. Clearside plans to resubmit the NDA in early 2020.
Among the supplementary approval decisions, Gilead’s Descovy looks like a shoe-in for approval in HIV pre-exposure prophylaxis following a positive panel vote in August, at least in men and transgender women who have sex with men; the committee cited a lack of evidence in cis-women.
Alexion’s Soliris follow-on, Ultomiris, could get the nod in its second indication, atypical haemolytic uremic syndrome, adding to its existing use of paroxysmal nocturnal haemoglobinuria. The company is trying to switch patients to the newer product as Soliris biosimilars approach; however, Soliris's intellectual property recently took a double whammy when the US Patent Office agreed to begin an inter partes review filed by Amgen, and the European Patent Office declined to issue two new patents.
Johnson & Johnson and Bayer’s blood thinner Xarelto, meanwhile, could have a tougher time in the prevention of venous thromboembolism in medically ill patients. J&J persevered here despite the failure of the Mariner trial last year – the company will have to hope that the totality of the data will convince the FDA (ESC 2018 – J&J not downhearted after Xarelto stumbles, August 28, 2018).
Glaxosmithkline’s Parp inhibitor Zejula is facing a decision in ovarian cancer patients with BRCA mutations who have received three or more chemo regimens. But all eyes will be on data from the Prima study, in first-line disease regardless of BRCA status, due for presentation at Esmo this weekend.
And some time in the fourth quarter Pfizer will hope to gain ground on its prostate cancer rival J&J: the former is due an approval decision on Xtandi in metastatic hormone-sensitive disease, a use for which J&J’s Erleada recently got the go-ahead.
|Supplementary and other notable approval decisions due in October|
|Descovy||Gilead Sciences||sNDA for HIV pre-exposure prophylaxis||Oct 5 (estimate)|
|PF708||Pfenex||Biosimilar Forteo||Oct 7|
|Zilretta||Flexion Therapeutics||sNDA for repeat administration for osteoarthritis pain||Oct 14|
|Xarelto||Johnson & Johnson/Bayer||sNDA for venous thromboembolism in medically ill patients||Oct 14 (estimate)|
|Nplate||Amgen||sBLA for pts with ITP for 12 months or less||Oct 19 (estimate)|
|Ultomiris||Alexion Pharmaceuticals||sBLA for atypical haemolytic uremic syndrome||Oct 18|
|Stelara||Johnson & Johnson||sBLA for moderate-to-severe ulcerative colitis||Oct 20 (estimate)|
|Baxdela||Melinta Therapeutics||sNDA/BLA for community acquired bacterial pneumonia||Oct 24|
|Zejula||Glaxosmithkline||sNDA for fourth-line ovarian cancer with BRCA mutations or HRD||Oct 24|
|Belviq/Belviq XR||Eisai||sNDA for cardiovascular outcomes data||Oct 25 (estimate)|
|PF-06410293||Pfizer||Biosimilar Humira; FDA accepted filing in Jan 2019||October (estimate)|
|Fluzone Quadrivalent||Sanofi||sBLA for influenza vaccine – high dose||Q4|
|Xtandi||Pfizer/Astellas Pharma||sNDA for metastatic hormone-sensitive prostate cancer||Q4|
|HRD: homologous recombination deficiency; ITP: immune thrombocytopenic purpura. Source: EvaluatePharma.|
This story has been updated to clarify Vumerity's likely approval date and Eylea's dosing schedules.