Sofosbuvir and Daclatasvir are BCS class I drugs. What that means is that they are highly soluble in water and get into the body easily.

Ledipasvir, Velpatasvir and Simeprevir are all essentially insoluble BCS class II drugs. This does not make them unusable (70% of all our drugs are like this) but it does mean there is more too it than simply ingesting them.

www.sciencedirect.com/science/article/pii/S1818087614000348

One technique to make insoluble drugs dissolve and get into the body is to change them. With simeprevir it is made into a sodium salt to aid solubility, however with simeprevir there is another issue: related substance C. This report is partially redacted but what you can see is that the originator had to apply for an exemption to allow more than the usual maximum quantity of impurity to be present and furthermore that this impurity is known to be toxic.

www.pmda.go.jp/files/000153596.pdf

With ledipasvir and velpatasvir they need to effectively be ground extremely finely so that there is a very large surface area to dissolve. There are a variety of ways to achieve this goal, but nevertheless it must be done. Micron size grinding - to 1 um is one approach and as you may have read from the article above there are many others. The goal is to make the API as small as possible. We used micronisation and the SVR rates we've seen provide reassurance that has been effective.

I have it on good authority that generic Sof+Vel will be available within 30 days so suggest anyone contemplating its use get something that has been formulated by experts - in other words don't try this particular trick at home.

Hmmm ... so I'm guessing somebody in Bangladesh is about to win a race to market again. My money is on Incepta.

Edit: I asked this on another thread, but it actually belongs here ....

Is the compounding process for Velpatasvir something which can be done by any compounding chemist, i.e., Kingswood?

One of the leading generic manufactures in India has an internal meeting July 17th on Velpatasvir. This will go through similar process as Sof and Sof+Led

1. Extensive licensing with patenting company(already done). Estimated number of companies to sell the licensed product is 11
2. Drug Controller General of India(DCGI) approval.

Current estimates are its going to take longer than 1 month.

We will know more post the July 17th meeting.

Solubility is relative. Compared to Velpatasvir Ledipasvir is soluble enough under acid conditions to have a lot more wiggle room and real world SVR rates of 93.4% overall are solidly in line with expectations.

Regarding simeprevir ..

It is my understanding that Janssen uses simeprevir sodium in their branded Olysio, Sovriad and Galexos capsules. The simeprevir API currently available from China is not the sodium salt and therefor of questionable use.

The linked disclosure of a cardiotoxic impurity (Related Substance C) present in the simeprevir manufacturing process poses a greater complexity.

From my reading - Johnson & Johnson (Janssen) has been seeing a substantial decrease in demand for this medicine. Aside from the recommended use in retreatment - is there a market for simeprevir based medicines sufficient to warrant the development of a generic ??

Certainly J&J has studied this ad nauseam - curious to know what folks here are seeing in the real world.

J

PS: Note that simeprevir (Olysio) is part of my upcoming retreatment plan. Current retail price here in the States is $22,500 USD for 28 capsules (150 mg). 24 weeks makes for $135,000 for this component alone. Outrageous ..

Hello!
Could someone possibly share information regarding the India launch and what's the state of affairs?

It's really anyones guess:

www.fiercepharma.com/pharma-asia/hcv-dru...irms-to-make-epclusa

Accelerated stability testing and then DCGI approval both need to be navigated before it hits the market. There may be other contractural restrictions that are delaying it. There was not a lot of logical reason for the > 6 month delay between generic Sovaldi and generic Harvoni (given both had been FDA approved, tech transfer done, etc.

MonkMed wrote:

Currently only Beacon and Incepta in Bangladesh have a generic.

Indian Sof+Vel will appear but it will be here when it's here. The DCGI stage can take a while.