In one of the biggest approval decisions of the year, Novo Nordisk’s oral version of semaglutide has got the US green light. But big questions still hang over the drug, now branded Rybelsus, including whether it will get a label for cardiovascular risk reduction, and how much it will really cost.
On the latter, all Novo is saying is that Rybelsus’s US list price will be “similar” to that of its once-weekly injectable sema, Ozempic. However, this is before taking rebates into account, and the post-rebate price tag might not become apparent until sales figures emerge next year.
Currently, EvaluatePharma sellside consensus forecasts Rybelsus’s 2024 revenues at $3.3bn; the drug’s ultimate price will be an important factor in whether it meets these expectations and becomes one of the biggest products launched in 2019.
|Top five drug launches in 2019, by 2024 sales|
|Annual sales ($m)|
|Company||Product||Indication; description||Approval date||2020e||2022e||2024e|
|Abbvie||Skyrizi||Psoriasis; anti-IL-23 MAb||Apr 2019||678||2,122||3,726|
|Novo Nordisk||Rybelsus||Diabetes; oral GLP1 agonist||Sep 2019||393||1,749||3,335|
|Abbvie||Rinvoq||Rheumatoid arthritis; Jak1 inhibitor||Aug 2019||347||1,608||3,054|
|Alexion Pharmaceuticals||Ultomiris||PNH; anti-complement factor C5 MAb||Dec 2018||949||1,814||2,470|
|Novartis||Zolgensma||SMA; gene therapy||May 2019||1,060||1,861||1,933|
At least investors now have an idea, albeit a rough one, of Rybelsus’s cost, which will be in line with Ozempic’s list price of $26 per day. Before the approval, Bernstein analysts had speculated that Rybelsus would be slightly cheaper, at $20-22 per day.
The post-rebate price tag will be another story. For injectables this is around $15-17 per day, and oral sema might need to come in lower than this to capture market share and compete with other, less expensive branded oral diabetes drugs like the SGLT2 inhibitors. Continued pricing pressure in the US diabetes market will not help Novo, either.
Bernstein analysts believe the actual price of Rybelsus could go as low as $10 per day, though they conceded that this was on the low side of expectations.
Novo’s chief scientific officer, Mads Krogsgaard Thomsen, would not be drawn on the company’s rebating plans, telling Vantage that the group was only just starting negotiations with payers. But he said that a comparable price to that of injectables was justified by Rybelsus’s clinical performance, as well as improved adherence with oral drugs.
Novo needs to pull off a delicate balancing act if it is to launch Rybelsus without cannibalising Ozempic too much. During a conference call today the group’s chief financial officer, Karsten Munch Knudsen, contended that there should be “plenty of space” for both products, given that Rybelsus’s main rivals will be other oral diabetes drugs; however, he admitted that there would be some impact on Ozempic.
The picture is further complicated by the expected entrance in 2024 of generic versions of Victoza, Novo’s once-daily injectable GLP1. The company will have to hope that convenience wins out, but it seems likely that generics will hit the entire class.
Cardiovascular decision coming
Meanwhile, Novo is due a decision from the FDA in January on the cardiovascular indication for both Rybelsus and Ozempic, based on pooled data from the Pioneer 6 and Sustain 6 studies (Novo’s next big diabetes bet heads to regulators, November 26, 2018).
The trials found a respective 21% and 26% reduction in major adverse cardiovascular events with semaglutide versus placebo. But Pioneer 6 showed non-inferiority, not superiority, while Sustain 6 did not include a prespecified superiority analysis – hence the pooling of the data.
So it is far from clear whether either drug will get the cardiovascular go-ahead next year, and Novo might have to wait for data from bigger cardiovascular outcomes trials such as the 9,600-patient Soul study of Rybelsus, which began earlier this year.
This is not set to complete until 2024, but an interim analysis could provide a chance for an earlier win. Exactly when this happens will depend on how quickly Novo can recruit patients and how soon events occur; all Mr Thomsen would say was that recruitment was “going well”.
Starting Soul before getting a cardiovascular decision looks like an expensive – but probably necessary – insurance policy. EvaluatePharma Vision’s R&D cost model estimates that Soul will set Novo back around $300m.
Another big opportunity for Novo is obesity, where the Select cardiovascular outcomes trial of Ozempic is ongoing. A more immediate indication of whether the product has a future here will come with data from Step 1, the first trial in the pivotal Step programme, next year.
|Selected semaglutide outcomes trials|
|Project||Trial||Description||N||Trial ID||Primary completion|
|Rybelsus||Soul||CV outcomes in T2DM and heart disease||9,642||NCT03914326||Jul 2024|
|Ozempic||Step 1||Weight loss in overweight/obese pts||1,950||NCT03548935||Mar 2020|
|Step 2||Weight loss in T2DM non-insulin pts||1,210||NCT03552757||Mar 2020|
|Step 3||Weight loss with Ozempic plus intensive lifestyle programme||611||NCT03611582||Mar 2020|
|Step 4||Weight loss maintenance||902||Feb 2020|
|Select||CV outcomes in obesity and CV disease||17,500||NCT03574597||Sep 2023|
|Flow||Cardiorenal outcomes in T2DM and chronic kidney disease||3,160||NCT03819153||Aug 2024|
|Focus||Eye outcomes in T2DM and diabetic retinopathy||1,500||NCT03811561||Feb 2025|
|Source: EvaluatePharma, clinicaltrials.gov.|