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.
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.
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)|
|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|
|–||–||Feb 2017||Marathon||None; asset sold to PTC Therapeutics|
|–||–||Nov 2017||Chemo Research||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.