Replies to post #251746 on Biotech Values

[Mufaso]

MDGL- Rezdiffra supposedly has coverage currently in place for 30% of the US according to the article you referenced:

Commercial coverage for Rezdiffra is currently in place for 30% of U.S. lives, tracking in line with Madrigal’s goal to reach 80% by the year’s end, according to Sibold.

I assume these insurers do not require biopsy for diagnosis or I assume it would vave been noted by the VA.

Noninvasive testing and what insurers will do has always been the key question for MASH drugs. It looks like MDGL is starting off pretty well in this regard. According to Madrigal (at the JPM conference in January/at their approval cc) most hematologists/GI and specialists who are treating MASH don't use Liver biopsies to diagnose MASH severity anymore. These specialists have been using Fibroscan ( FibroScan is a type of liver elastography using ultrasound) and FIB4 blood tests. My understanding as these tests together have become the new defacto gold standard for diagnosis of MASH.

Regarding the VA requirement to have a biopsy, I assume they are simply delaying the process as MDGL suggests. The FDA label doesn’t require it as it appears most Experts don’t think it’s the current standard so it appears they are an outlier.

Now that a drug is approved for MASH, I would be interested in any legal opinions anyone has (Mouton?) on whether insurers would have any liability if they denied or delayed coverage because of the biopsy requirement that led to a bad outcome (e.g. liver cancer) Would this make insurers more likely to not require a biopsy?

Also- does anyone have a legal opinion if insurers could refuse to cover MASH for a covered person now that a drug is available and what legal liability they might face for non-coverage?

[Mufaso]

MDGL- Recently I came across some old notes that I never posted on what Madrigal said at JPMorgan back in January but never posted them. I was going to post something when MDGL got approval for Rezdiffra but got busy and never did. I did listen to MDGL’s cc when they got approval and they said the same things they said at JPM except they got clarity on the label which was as good as could be expected in that no Biopsy would be required for diagnosis treatment.

In any event I thought it would be worthwhile to post what CEO Bill Siebold said back in January to what has transpired since. In many respects, everything he said has tracked with what happened and is happening now so he appear to have a really good handle on reality. (Bill Sibold was at Sanofi Genzyme and heavily involved with Dupixent and looks to have a pretty impressive track record.)

Here are my old notes from January:

- While there are 1,500,000 diagnosed with NASH, and 525,000 have significant fibrosis only 315000 are actually seeing specialists (F2/F3) - these 315,000 are the target patients MDGL is pursuing. (Source - Forian Claims Data)
- ICER (Institute for Clinical and Economic Review) cost effectiveness is $39,5600 to $50,100 (Mufaso update- MDGL list price for Rezdiffra set at 47k)
- Don’t think Label will support F4 use and won’t go after it. (Mufaso update- Label doesn’t support F4 usage)
- MDGL is conducting “Outcomes trial” (in well compensated Nash (f4) currently looking at this which will take 36 months) F0 and F1 managed other ways.
- Its progression of Fibrosis that leads to bad outcomes
- 1st program to hit on both NASH Resolution and >= 1 stage fibrosis improvement. Plus impressive LDL cholesterol data
- Depth of response is 90% when you have had either NASH Response or >=1 stage fibrosis improvement
- Note- Placebo effect where there was a liver fat reductions was only associated with NASH res and not Fibrosis improvement-very important point when comparing to GLP1’s (Mufaso update note- this was before the data on Tirzepatide in the SYNERGY-NASH trial became available which suggested Tirzepatide had a “clinically meaningful” effect on fibrosis improvement. See #msg-173784185)
- Safety- when patient pop is on other drugs- noted that discontinuations were higher in placebo at 52 weeks than resmetirom - also placebo and TEAEs were similar between placebo and treatment arms- also in 100mg group most AE discontinuations were GI related with incidence decreasing after first few weeks
- No drug induced Liver injury events (DILY)
- Ready to go with specialty launch on Mar 15th (hiring now) - not just hiring for launch but for 2-3 year period (CEO worked with Dupixent) Will stay focused where they studied (F2 and F3)
- Have patients that are waiting for this drug to be approved…
- Will biopsy be required? – Don’t think Biopsy will be part of label or indication. Not sure yet on label because first- even if label is broad – not changing who they go after and if its narrow (f2 f3- that’s fine- when they have data in F4 from outcomes trial and then it would be a target (Mufaso update- the label did not require biopsy for diagnosis so MDGL/Sibold was spot on back in January on this point)
- EPI numbers are larger that everyone has heard- who already had a coding for NASH (is 1.5 Million) see below for EPI definition (Mufaso note- I didn't know what "EPI" was so I looked it up- Epi Patient Based definition->Epidemiological or epi-based forecasting. This is a patient-based approach where the starting point is typically a country’s population or sub-population based on age or gender. Then a disease prevalence rate, a diagnosis rate and a treatment rate are applied. This defines a target population in terms of number of treated patients.)
- Still need to have conversations with payers.
- How will patients diagnosed? MDGL understanding that only 2-3% of patients have biopsy- one of the challenges is Biopsy takes a narrow piece and not definitive (not like basel cell carcinoma)- newer experts moving away from biopsy because there are other NIT techniques that allow diagnoses with certainty in these experts view-that is a - combination of blood tests and imaging- right now the standard is fib4 and Fibroscan – other like MRI and MRE and Blood work like Elf – right now no one paying attention cause what do you do- no drug available till now- think everyone will figure out how to sequence tests
- GLP1 perspective – one big diff – they have clinical data on reversal of fibrosis- pdff placebo helped validate this - does it translate to MOA- they think so…GLP1 can play in the area where you try and prevent. But for someone who has NASH F2/F3, you take time to do titration of dose and more- will you be willing to wait to see if weight loss has impact before fibrosis progresses?

Overall, the MDGL plan seems to be a realistic one and they will be on the market without competition for at least 3 years.