The FDA’s swift review of givosiran, the second RNAi-based therapeutic to win marketing approval, speaks to growing comfort with this technology across the industry. From a string of hefty deals struck by Dicerna recently to Alnylam’s success at getting its projects on to the market, the RNAi field is making great progress.
Givosiran, which will be sold as Givlaari, was approved two and a half months ahead of its PDUFA date, and around five and a half months after it was first submitted to the FDA. This speed is laudable for a novel technology in a rare disease space, but the approval is far from the quickest regulatory action seen, as the below analysis reveals.
The numbers below are based on the date the FDA receives an application, which is recorded in the official approval decision letter; companies frequently cite timelines based on acceptance of an NDA when boasting of quick decisions, presumably as this method will lead to a smaller number. However acceptance of an NDA is left up to companies to announce and the inevitable gaps in disclosure make a thorough analysis tricky.
|Fastest FDA approvals*|
|Product||Company||Indication/mechanism||Review status||FDA approval date||Approval time (months)|
|Blincyto||Amgen||ALL/anti-CD19 Mab||Breakthrough therapy||Dec 3, 2014||2.5|
|Jevtana||Sanofi||Prostate cancer/taxane||Priority review||Jun 17, 2010||2.6|
|Iclusig||Ariad||ALL & CLL/BCR-ABL & pan-FGFR inhibitor||Priority review||Dec 14, 2012||2.6|
|Spinraza||Biogen||SMA/SMN 2 antisense||Fast track||Dec 23, 2016||3.0|
|Xtandi||Astellas/Medivation||Prostate cancer/androgen receptor antagonist||Priority review||Aug 31, 2012||3.3|
|* Since 2007. Source: EvaluatePharma.|
This is not to detract from Alnylam’s achievement here: approved for the rare condition acute hepatic porphyria, Givlaari is the first therapy to reduce the frequency of painful attacks that plague suffers of this condition. Exactly how many patients are out there is still unknown, hence the use of the novel payment structure.
To make Givlaari’s list price of $575,000 per annum more palatable Alnylam has worked with Harvard Pilgrim to include both a value-based agreement and an industry-first prevalence-based agreement.
Under the value-based deal, the full price of Givlaari will only be payable if patient outcomes in the real world are similar to those achieved in clinical trials. This payment metric is becoming increasingly common, but it is arguably a bold move given that most trials are structured to include the patients thought most likely to benefit.
What marks the Alnylam arrangement out as truly innovative is the prevalence-based agreement. This is designed to stop costs ballooning for payers in the event of unexpectedly large patient numbers. Rebates will be triggered if the number of diagnosed patients exceeds the epidemiologic estimates for AHP; Alnylam believes 3,000 patients in the US and Europe could qualify for treatment.
The AHP market has proven hard to size due to the difficulty of diagnosis and limited physician awareness of the disorder. But the biopharma sector's interest in rare diseases is showing no sign of waning, so it seems likely that these arrangements will become more common.
Alnylam reckons Givlaari sales could reach around $500m. The sellside is slightly more optimistic. Consensus currently sits at $416m in 2024, with peak sales reaching almost $700m, according to EvaluatePharma. Early comments from financial analysts hint at little change to those numbers for now, though how the product fares in the coming year will closely scrutinised.