Drug repositioning in Castleman disease

What is drug repositioning?

Repositioning consists of identifying drugs that have already been approved by the health authorities and that could be effective in diseases for which they are not currently indicated. 

Indeed, health products are subject to very strict regulation to ensure the safety of the patients who use them. All available medicines have a so-called marketing authorisation issued by the health authorities.  

This authorisation specifies a list of indications for which the medicine may be prescribed and dispensed to patients.  

For example, Ventolin® is indicated for the treatment of asthma attacks or the prevention of exercise-induced asthma. This medicine can only be dispensed and covered by insurance companies if the indication corresponds to that mentioned in the marketing authorisation. 

The aim of drug repositioning is therefore to broaden the indications of drugs already on the market. 

What are the advantages of drug repositioning?

Drug development is a lengthy and expensive process. On average, it takes 13 to 15 years and several billion dollars to bring a new molecule to market. 

Using repositioning allows us to avoid the development stages, which include ensuring the safety and tolerance of the drug. It therefore saves considerable time and money.  

This approach also makes it possible to benefit from the knowledge already acquired about the drug from both clinical and preclinical data, as well as from the pharmacovigilance phase conducted after the drug was placed on the market.

How can a single drug be indicated for several diseases?

Most of the time, the active ingredient of a drug has more than one cellular target in the human body. When developing a drug, laboratories focus on the effects of a molecule in relation to a specific disease. It is therefore possible that this drug has other effects in other diseases without clinical trials being able to reveal them. 

These effects are often discovered after the drug is marketed. For example, it may be discovered that a cholesterol drug also has an effect on blood pressure. It may then be repositioned as an anti-hypertensive. It is often when beneficial side effects are discovered that molecules are repositioned. 

The therapeutic arsenal available on the market is made up of approximately 2,500 pharmaceutical specialities. Unfortunately, all of these drugs cover only 25% of the 10,000 identified human diseases.

Many of these orphan diseases (disease affecting a very small population) are rare and fatal

Because of their rarity, diseases such as CD do not represent a sufficient commercial stake for pharmaceutical companies to actively seek to develop new molecules.

In contrast, organisations such as the Castleman Disease Collaborative Network (CDCN), which work on research into new treatments, do not have sufficient resources to carry out the development of new molecules.

A quicker and much cheaper solution for these organisations is therefore to use drug repositioning to discover and use the full potential of drugs already on the market. 

The CDCN's approach to drug repositioning is to first study biological samples from patients to identify the cellular markers and signalling pathways involved in the disease. Once this data is acquired, research will be carried out on available drugs targeting these markers.  

Then, since these drugs have been identified, clinical trials can be conducted. 

To learn more about the CDCN, you can read our article on the CDCN's unique approach to accelerating research.

Drug repositioning in CD: Sirolimus

Dr. David Fajgenbaum, a doctor who co-founded the CDCN and himself has idiopathic multicentric CD (iMCD), began testing sirolimus on himself in 2014 after the treatments he had been prescribed failed.  

Sirolimus is a drug indicated for the prevention of kidney transplant rejection in post-transplant patients. In 2015, it had already been repositioned in the treatment of another rare disease.  

Sirolimus is a drug appropriate for the prevention of kidney transplant rejection in transplanted patients. In 2015, it had already been repositioned in the treatment of another previously rare disease. It is an oral immunosuppressant that blocks a process within human cells called the m-TOR signalling pathway.  

The drug slows down the immune system and thus limits the hyperactivity that causes relapses in CD. 

The CDCN's work with sirolimus has allowed it to be used in other iMCD patients who did not respond to siltuximab. Siltuximab is a first-line treatment for iMCD, but unfortunately it is ineffective in about 2 out of 3 patients.

The alternative offered by sirolimus has helped to keep about 20 patients who did not respond to siltuximab in remission and is currently undergoing a clinical trial in the US with the aim of obtaining health authority approval for this new indication. 

In 2019, a study including three patients with iMCD who had not responded to siltuximab showed that sirolimus enabled them to enter remission.

For further reading:

Please visit the Castleman Disease Collaborative Network (CDCN) website for more information. 

You can also join the Castleman Disease forum on Carenity to share your experience, find support and exchange information with other patients or relatives. 

If you are interested in making your voice heard, let us know! Share your experience of Castleman disease (diagnosis, journey, treatments, etc.) with our members.  

Would you like to share your story? Contact us at this address: contact@carenity.co.uk 

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