How do we mark the dawning of a new age? As I think about what the first drug for NASH means I recall the journey we have been on.  In the beginning the liver was too complicated but early successes promised answers only to fail again and again. We rode the waves of optimism and crashed on the rocks when drug candidates failed. So many of us were told by our docs, you have NASH and I'm sorry but we have no treatment. How shall we note this day when the first treatment is approved? 

Most people don't realize just how much Becky Taub, the scientist at the center of this tale, has devoted to the cause of liver patients.  She was with Hoffman-La Roche from 2004-2008 when the link between thyroid hormones and fatty liver disease was proposed and the molecule that became Resmetirom was considered. Throughout her career she was involved in the study of metabolic diseases. Via Pharmaceuticals, founded in 2004, became Madrigal In 2016 and acquired the rights to the molecule. She has steadfastly focused on the development of the drug which we now have available as the first treatment for NASH. Imagine devoting decades to the development of a single product. How easy it would have been to give up at times as the seemingly endless list of issues presented themselves. We all owe Becky a huge debt of gratitude for persisting in the quest for answers.

How do I express how we feel at this important moment?  There is a miracle of music composition by Leonard Cohen that for me expresses how I feel about the journey we have been on.  It is an allegorical journey to the heights of hopefulness and the depths of disappointment leading finally to success.  A symbolic journey but very powerful. Before we start looking at drug details click this link and take a few minutes to enjoy.

Halleluiah, we have a treatment at last

If you would like a bit more background, here is a link to an earlier blog about Madrigal with a different focus.

www.fattyliverfoundation.org/madrigal_presents

OK, enough melodrama, some facts about this drug. We will provide more details in the future but these are the basics.

PATIENTS ELIGIBLE

REZDIFFRA is a thyroid hormone receptor-beta (THR-beta) agonist indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).  It is given as a once daily pill with dosage adjusted for patient weight. NOTE: It is not approved for F4 cirrhosis patients at this time.

WHAT ARE THE POSSIBLE SIDE EFFECTS OF REZDIFFRA?

This list will look familiar as these are common complaints.  Some patients experience increased symptoms but they are generally mild and diminish over time.

• REZDIFFRA may cause serious side effects, including:
• liver injury (hepatotoxicity). Stop taking REZDIFFRA and call your healthcare provider right away if you develop the following signs or symptoms of hepatotoxicity: tiredness, fever, pain or tenderness in the upper middle or upper right area of your stomach (abdomen)
• nausea
• rash
• vomiting
• your skin or the white part of your eyes turns yellow (jaundice)
• gallbladder problems. Gallbladder problems such as gallstones, or inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur with NASH and may occur if you take REZDIFFRA. 
• The most common side effects are: These will be familiar
  • diarrhea • itching • vomiting • constipation
  • nausea • stomach (abdominal) pain • dizziness

WHAT IS THE COST OF THE DRUG?

The list price is $47,400 annually.  This is about the midpoint of the cost benefit analysis done by ICER and is similar to other specialty medications.  Insurance payors have generally not expressed resistance to the pricing.  The expected co-pay is $10 but may vary with the plan.

What about the uninsured or under insured?  We will discuss this in detail in future blogs, but Madrigal is developing processes to assist these patients.  They have stated that it is their goal to see that all patients who should be treated have access to the drug even if they have to give it away for free.  Quite a commitment to patient health.  Details to follow.

WHEN WILL IT BE AVAILABLE?

It is anticipated that it will take 60 days before the first prescriptions can be filled so expect the pipeline to begin filling by mid summer.  Physicians are expected to manage patients in their normal flow and most will not make a big push to pull patients in early given that the F2/F3 population is not generally in immediate danger.

HOW SHOULD YOU THINK ABOUT THIS DRUG

It is important not to imagine this as a silver bullet.  Your first line of therapy will still be diet and exercise.  It will be beneficial to a significant segment of the patient community but it is really the first shaky step to robust treatments.  There is still a long way to go before all of the urgent questions are answered and we can think of liver disease as having treatments but as the first it is a very valuable contribution to patient health and will save lives.

If you would like to look at the patient prescribing information, here is a link to a patient friendly version of the label information.

www.madrigalpharma.com/Patient-Prescribing-Information.pdf

More to come in future blogs, but for now enjoy the moment.