Go or no go? GSK takes its turn with a novel anaemia class

Amicus and Astrazeneca have notable approaching Pdufa decisions, while a panel for GSK’s daprodustat could change the course of a controversial drug class.

A handful of notable first-time approval decisions stand out in October, for Amicus, Astrazeneca and Johnson & Johnson, although the spectre of delay hangs over several ongoing reviews. The FDA continues to struggle with a backlog when it comes to inspecting ex-US manufacturing plants owing to Covid travel restrictions.

Two advisory committee hearings will also be getting attention next month. Covis will face a two-and-a-half day grilling over its controversial preterm birth drug Makena, while GSK will attempt to change minds on the HIF-PH inhibitors in anaemia during the review of daprodustat.

First to approvals, where biopharma followers are hoping to see a pick-up in the final quarter after a slow year. Several reviews are stalled due to the inspection issues, and Amicus will be hoping it does not join that list.

Alongside second-quarter earnings in early August the company said that the FDA had yet to inspect the Wuxi Biologics’ facility that makes ATB200, or cipaglucosidase alfa, the biologic component of Amicus's Pompe disease contender AT-GAA. But executives said they expected both components of the project to be approved together by the October 29 Pdufa date. The August 29 Pdufa date for the other agent, miglustat, was missed.

Any delay might mean a European approval comes first. The EMA has said it does not require an inspection of the facility and a CHMP decision is expected later this year.

Elsewhere, Astrazeneca will be keen to see tremelimumab over the finish line, after years of struggling to find a place for the anti-CTLA4 MAb. A green light would make treme only the second immuno-oncology agent with this mechanism to reach the US market, after Bristol Myers Squibb’s Yervoy.

Treme’s liver cancer filing was based on a roughly three-month overall survival benefit over Nexavar in the Himalaya trial. The US application was accepted with priority review in April, so a decision should be imminent.

And finally J&J is awaiting news on a contender in the increasingly crowded anti-BCMA space: teclistamab, a bispecific or “duobody” licensed from Genmab. The company already sells a BCMA-directed Car-T product, Carvykti, which carries substantially larger commercial hopes, with a 2028 consensus forecast of $683m.

Notable first-time US approval decisions due in October
Project Company Pdufa date Indication(s) 2028e SBI ($m) Note
SPN-830 apomorphine infusion device Supernus Early Oct Continuous treatment of motor fluctuations (off episodes) in Parkinson’s disease 198 Resubmission, previous refuse-to-file
Furoscix scPharmaceuticals Oct 8 (resubmission) Congestion in patients with worsening heart failure - Previous CRL (CMC)
Cipaglucosidase alfa (ATB200) for AT-GAA Amicus Oct 29 Pompe disease 266* Part of two-component therapy with miglustat (whose own decision has not come yet); could get delayed owing to manufacturing inspection
Tecvayli (teclistamab) Johnson & Johnson Q4 R/R multiple myeloma  260 Approved by EMA in August (BCMA bispecific)
Tremelimumab + Imfinzi (Stride regimen) Astrazeneca Q4 Unresectable hepatocellular carcinoma  364 Based on Himalaya study (Asco-GI – immuno-oncology makes progress in liver cancer)
Tislelizumab Beigene/Novartis Decision deferred pending manufacturing inspections 2L oesophageal squamous cell carcinoma - Original Pdufa Jul 12, 2022
Annik (penpulimab) Akeso/Sino No news 3L nasopharyngeal carcinoma - Approval expected H1
*For AT-GAA. SBI=sales by indication. Source: Evaluate Pharma, company releases.

Makena has had a long and contentious history and many hope that this adcom will finally lead to its withdrawal. Makena first won accelerated approval in 2011, and after a confirmatory trial failed in 2019 and a subsequent advisory committee voted against its ongoing use, the FDA formally proposed it be pulled from the market.

But its then-owner, Amag, objected, putting the wheels in motion for this next panel hearing. Makena is now owned by the private-equity owned Covis, which continues to advocate for its use. The outcome of the process will also impact five generic versions that are available.

The adcom considering GSK’s Duvroq (daprodustat) will also be closely followed, given the concerns voiced by the FDA and a previous panel about the cardiovascular safety of another member of this drug class, Astrazeneca/Fibrogen’s roxadustat.

Roxadustat and Akebia’s vadadustat were both handed complete response letters earlier this year. The panel that reviewed the former was particularly damning, although criticisms around disclosure and mishandling of data complicate the picture somewhat.

All are HIF-PH inhibitors, oral treatments for anaemia. Proponents consider these drugs a valuable new mechanism in the management of chronic kidney disease, with safety and efficacy equivalent to the Epo agents. GSK’s pivotal programme, presented earlier this year, was the cleanest seen so far, but the company could still have a tough job persuading the regulator and panel members that Duvroq’s benefits outweigh its risks given the history of this class.

The stance taken by the FDA has raised eyebrows, given that regulators in Europe and Japan have both approved roxadustat, which is sold by Astellas as Evrenzo in those regions. An EMA decision on Duvroq is expected early next year.

Advisory committee meetings due in October
Project Company Adcom date Indication 2028e SBI ($m) Note
Makena Covis Oct 17-19 Reduce the risk of preterm birth in women who have a history of singleton spontaneous preterm birth - Discussion around potential withdrawal of accelerated approval
Duvroq (daprodustat) GSK Oct 26 Treatment of anaemia due to CKD in adult patients not on dialysis and on dialysis 187 Evrenzo and vadadustat, also HIF-PH inhibitors, both received CRLs
Y-mAbs Therapeutics Oct 28 Treatment of neuroblastoma with CNS/leptomeningeal metastases 69 Previous RTF in 2020
Sohonos (palovarotene) Ipsen Biopharmaceuticals Oct 31 Prevention of heterotopic ossification in adults and children with fibrodysplasia ossificans progressiva 152 Resubmitted, previously withdrew as FDA requested additional analyses of data
SBI=sales by indication. Source: Evaluate Pharma, company releases, FDA adcom calendar.


Supplementary and other notable approval decisions due in October
Product Company Indication (clinical trial) Date
Oxlumo Alnylam Reduction of plasma oxalate in advanced primary hyperoxaluria type 1 (Illuminate-C) Oct 6
Abrilada (Humira biosimilar) Pfizer Interchangeability designation Q4
Lynparza + Zytiga + prednisone/prednisolone Astrazeneca Metastatic castration-resistant prostate cancer (Propel) Q4
Rinvoq Abbvie Non-radiographic axial SpA (Select-Axis 2 Study 2) Q4
Actemra Roche Hospitalised Covid patients (EUA in Jun 2021; EmpactaCovactaRemdactaRecovery) H2
Ronapreve (Regen-Cov) Regeneron Treatment of Covid-19 in non-hospitalised patients and as prophylaxis in certain individuals; given EUA in Nov 2020, limited Jan 2022 after emergence of omicron (NCT04425629NCT04452318) Pending
Source: Evaluate Pharma, company releases.

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