When is insulin aspart not NovoRapid?

I have a suspicion about some of the background to the current Fiasp drama, where Novo seems to have been pressured to remove Fiasp from PBS listing.

Stories are rarely simple. I don’t know this is the complete story, but I’ll try to stick to recounting known facts!

This is a potted history of one of the insulin analogs we use: insulin aspart. In its plain form this is regarded as a “rapid-acting” insulin. It’s a lot faster than the “short-acting” human “regular” insulins like Actrapid and Humulin. Although there are faster insulins today, insulin aspart is still classed as “rapid”, and new adjectives like “ultra-rapid” have been applied to the newer ones.

Multiple Players

I’ll start off by reminding you that there are 3 “big” insulin companies:

• Novo Nordisk (“Novo”)
• Eli Lilly (“Lilly”)
• Sanofi-Aventis (“Sanofi”)

But there also others, including Mylan.

NovoRapid

In late 2006 NovoRapid was approved by the TGA for use in Australia. The active ingredient in NovoRapid is insulin aspart. In the US the trade name is NovoLog, but it’s the same thing.

Companies tend to apply lots of patents to drugs where they can, which gives them exclusivity for a while. Insulin aspart was Novo Nordisk’s answer to Eli Lilly’s insulin lispro (sold as Humalog). No-one else could make/sell aspart.

But in 2014 these patents started expiring, and generic versions of insulin aspart started appearing from other manufacturers. Sometimes these are referred to as “biosimilars”. Mylan have one called Kristy. Sanofi have at least two: Trurapi and Truvelog. If they can show it’s the equivalent product, they can then compete with NovoRapid/NovoLog on price. Novo have themselves introduced a generic “Insulin Aspart” to compete.

FIAsp

So no-one should have been surprised to see Novo bring a new form to market: “Faster Insulin Aspart”. Of course with a new suite of patent protection. In 2017  FIAsp got approval in Canada, Europe, and Australia. Other countries followed. Of course, it was a while before it actually reached the market in some of those countries.

Interestingly, Fiasp is essentially insulin aspart accelerated with a tiny amount of niacinamide. It starts working a lot sooner than NovoRapid, and fades away sooner. But it’s officially listed as still being “insulin aspart”. This apparently made it easier to get it through the bureaucracy in some countries, as it was just a new form of an existing known drug. But Novo’s competitors still can’t sell “faster insulin aspart”.

In countries like Australia where prescriptions are now made out for the generic medication name and not a brand name, this has meant a prescription for “insulin aspart” could get dispensed as either NovoRapid or as Fiasp (unless the particular format was also specified).

Incidentally, it’s presumed that limitations on the number of forms of the same medication that can be listed on PBS were behind the mess of Fiasp not being available in Penfill form (only pre-filled pens and in 10mL vials).

Other insulin patents expiring

Sanofi’s Lantus (insulin glargine) also had a patent expiry issue, after which they introduced a new longer-acting form (Toujeo). There are generic versions, including Optisulin (from Sanofi themselves), Semglee (from Mylan), and Basaglar (from Lilly). Mylan introduced Semglee into Australia in 2019, but they withdrew it from the market in early 2022: they didn’t quite carve a big enough niche for themselves in the market.

When the patents on Novo’s long-acting Levemir (insulin detemir) expired, amazingly they were able to come up with the even longer-acting Tresiba (insulin degludec).

Eli Lilly’s Humalog (insulin lispro) is older than insulin aspart, and after its patent expiry Lilly introduced the accelerated Lyumjev (insulin lispro-aabc). Lyumjev is even faster than Fiasp.
Lilly still sell Humalog, but in some markets they also sell “Insulin Lispro” at a lower price point, and Sanofi have a version they call Admelog.

Truvelog

In 2020 Sanofi’s Truvelog received TGA approval for supply in Australia. In January 2022 I commented (in this article) that they had applied to get it listed on PBS, which is when they can really compete with other insulins and start moving product.

Applications start with the PBAC (Pharmaceutical Benefits Advisory Committee) who consider both medical benefits and cost issues, give feedback to the sponsor, and either recommend for or against adding the medication. But then the final decision is made elsewhere within the Health Department.

After their November 2021 meeting the PBAC recommended for the PBS listing of Truvelog. Not because it represented any “substantial and clinically relevant improvement” over NovoRapid, but on the basis of its equivalence to NovoRapid and basically because it was likely to save the Government money. Like other generics, it could be substituted at the pharmacy level without having to get a different prescription.

However, Truvelog has not yet appeared on PBS. Presumably it’s in the pipeline though.

Is this affecting Fiasp?

With a new option of an “insulin aspart”, presumably the Health Department bean-counters have been talking to Novo about the price they pay for other forms of insulin aspart.

Because Fiasp is classed as the same medication as NovoRapid (although the timing of its behaviour is different enough to make a major impact on the lives of its users) this may be part of the story behind a price war between Novo and the Government.

Unfortunately it seems that said bean-counters may not have considered that the clinical behaviour of Fiasp is not the same as NovoRapid or Truvelog.