Astra could use a voucher to cement roxadustat’s head start

Spending $95m to speed up the anaemia project’s path to approval could be worth the investment for Astrazeneca.

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The market for priority review vouchers isn’t what it used to be. And Astrazeneca looks like it has bagged a relative bargain, paying Sobi $95m to get a head start for one of its pipeline candidates.

Astra has not yet said if it has a particular therapy in mind for the voucher, but its anaemia project roxadustat seems like a good bet. The Fibrogen-originated asset is vying with several others in the same class for a piece of what is expected to be a multi-billion dollar market.

Under priority review the US FDA aims to make an approval decision within six months, versus the standard 10-month review. Companies have therefore used the vouchers when there is a good reason to hasten a drug to market, for example where competition is set to be fierce and first-mover advantage could be vital.

Another contender for the voucher might be trastuzumab deruxtecan, an Her2-targeting antibody-drug conjugate that Astra licensed from Daiichi Sankyo in March. However, the companies are pitching this as a better version of the well-established drug Herceptin, so time is not exactly of the essence here.

It is worth remembering that Astra now has two priority review vouchers, having gained another, still apparently unused, from Wellstat in 2014.

Perhaps Astra just saw a chance to get its hands on a voucher at a good price, particularly as these were changing hands for as much as $350m at their peak. But as more US priority review vouchers have been issued following the programme’s 2016 reauthorisation their resale value has fallen. The $95m Astra has given Sobi is in the $80-105m range of this year’s three other disclosed voucher sales.

A net total of eight existing vouchers are thought not to have been sold on or redeemed, though additional vouchers might have been issued without this fact having been disclosed.

Anaemia race

Roxadustat does look like an ideal candidate for the voucher. The project is one of several HIF-PHI inhibitors in late-stage development, and the market could be very large indeed: Stifel analysts note that the erythropoiesis-stimulating agents HIF-PH developers are hoping to displace sell around $6bn per year. 

Roxa currently leads the race, but cementing this head start could be invaluable. The project is set to be submitted to the FDA in October; if approved, Astra will be responsible for US commercialisation.

Competitors are not too far behind. Akebia's vadadustat and Glaxosmithkline's daprodustat are both filed in Japan, but the US will be the main battleground, and both projects are due to yield phase III data in late next year. 

The late-stage HIF-PH inhibitor race
Project Companies Status 2024e sales ($m) Note
Roxadustat Astrazeneca/Fibrogen/ Astellas Approved in China, US filing due Oct 2019 1,373 Full US/EU data to be presented at ASN in November 
Vadadustat Akebia/Mitsubishi Tanabe/Otsuka Filed in Japan, US phase III data due 2020 929 Inno2vate (NCT02865850, dialysis-dependent); Pro2tect (NCT02648347, non-dialysis-dependent)
Daprodustat Glaxosmithkline/
Kyowa Kirin
Filed in Japan, US phase III data due 2020 383 Ascend-D (NCT02879305, dialysis-dependent); Ascend-ND (NCT02876835, non-dialysis-dependent)
Molidustat Bayer Japanese phase III trials ongoing 29 Miyabi ND-C (NCT03350321, non-dialysis-dependent); Miyabi HD-M (NCT03543657, dialysis-dependent)
Enarodustat Japan Tobacco/Torii  Korean phase III trial recruiting - NCT04027517, dialysis-dependent
Desidustat Zydus Cadila Phase III not yet recruiting - Dream-ND (NCT04012957, non-dialysis-dependent)
Source: EvaluatePharma, clinicaltrials.gov.

However, there are still question marks over roxa's safety following a confusing update from a pooled analysis earlier this year (Roxadustat safety analysis provokes more questions than answers, May 10, 2019). Toxicity concerns look like the only thing that might scupper roxa, which has met efficacy endpoints in pivotal trials in various settings. A priority review voucher would not be much help if the FDA did have worries here.

The safety question might be answered by the further US and European data that are due to be presented at the American Society of Nephrology meeting in Washington, DC, in November. Roxa is also likely to be the subject of a US FDA adcom next year.

Meanwhile, roxa was approved in China today for a new use: patients with anaemia caused by chronic kidney disease who are not dependent on dialysis. This adds to its Chinese approval last December in dialysis-dependent patients. Astra and Fibrogen plan to launch roxa in China, where they have a 50/50 profit share agreement, in the second half of this year.

Astra reckons it is several years ahead of its HIF-PHI rivals in China. In the US the stakes are higher, and timelines look tighter, so using the voucher could be a good move.

The fate of disclosed priority review vouchers
Date sold Price Date issued Issued company Action
Apr 2009 Novartis Redeemed by Novartis in BLA for Ilaris (gout)
Dec 2012 J&J Redeemed by J&J in BLA for Tremfya (psoriasis)
Oct 2015 Alexion Redeemed by Alexion in BLA for Ultomiris (PNH)
Aug 2017 Novartis Redeemed by Novartis in BLA for brolucizumab (AMD)
Jul 2018 Glaxosmithkline Redeemed by Viiv in NDA for Dovato (HIV)
Jul 2014 $68m Feb 2014 Biomarin Sold to Sanofi & Regeneron
Sep 2014 Not disclosed Sep 2015 Wellstat Transferred to Astrazeneca in licensing deal
Nov 2014 $125m Mar 2014 Knight Sold to Gilead, which redeemed it in NDA for Odefsey (HIV)
May 2015 $245m Mar 2015 Asklepion Asset sold to Retrophin, which sold PRV to Sanofi, which redeemed it in NDA for insulin glargine (T2D)
Aug 2015 $350m Mar 2015 United Sold to Abbvie, which redeemed it in NDA for Rinvoq
Q2 2016* ~$200m** Jun 2016 Paxvax Likely sold to Gilead and redeemed in NDA for Descovy (HIV)*
Feb 2017 $125m Sep 2016 Sarepta Sold to Gilead, which redeemed it in NDA for Biktarvy (HIV)
Nov 2017 $125m Apr 2017 Biomarin Sold to undisclosed party
Dec 2017 $130m Nov 2017 Ultragenyx Sold to Novartis, which redeemed it in NDA for Mayzent (MS)
Apr 2018 $110m Dec 2017 Spark Sold to Jazz Pharmaceuticals
Jul 2018 $81m Apr 2018 Ultragenyx Sold to undisclosed party
Nov 2018 $80m Jul 2018 Siga Sold to Lilly
Mar 2019 $105m Jun 2018 GW Pharma Sold, presumably to Biohaven#
Aug 2019 Not disclosed Jun 2018 Medicines Development Sold to Novo Nordisk##
Aug 2019 $95m Nov 2018 Novimmune Asset sold to Sobi, which sold PRV to Astrazeneca
Dec 2015 Alexion None
Dec 2016 Biogen/Ionis None
Feb 2017 Marathon None; asset sold to PTC Therapeutics
Nov 2017 Chemo Research None
Oct 2018 Leadiant None
Feb 2019 Novartis None
Feb 2019 Vertex None
May 2019 Sanofi None
May 2019 Novartis None
Aug 2019 TB Alliance None
Notes: Glaxosmithkline and Teva have bought PRVs from undisclosed sellers, for $130m and $150m respectively; these were redeemed in 2017 filings for Juluca (HIV) & Ajovy (migraine). *Gilead revealed purchase of undisclosed PRV in SEC statement; **based on Gilead disclosure of $624m increase in R&D spend, less $400m Nimbus purchase and undisclosed clinical trial progression; #to be used with Rimegepant Zydis; ##Novo redeemed a second PRV, obtained from an undisclosed source, in its NDA for oral semaglutide (T2D).

The table in this story has been updated to reflect information from Novo Nordisk about the company's two separate vouchers.

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