JAK inhibitors may fall to 2nd-line due to safety concerns

First-ever case recorded where authorities may make preemptive measures in response to the revocation of license, other than deletion from the reimbursement list

Health authorities are collecting opinion on clinical efficacy from academic societies, etc.

Prioritized safety in patient drug intake… is actively considering advancing regulatory science for public health

FDA restricts Xeljanz from first-line to second-line treatment in response to its safety issue

With the health authorities seriously considering changing the reimbursement standards for Janus kinases (JAK) inhibitors which have recently been caught up in controversy over its safety issues, what the results will be is gaining industry-wide attention.

 

According to industry sources, the Ministry of Health and Welfare (MOHW) and the Health Insurance Review and Assessment Service (HIRA) have been collecting opinions from relevant academic societies on the clinical efficacy and sequential therapy (first-line·second-line treatment) of JAK inhibitors for consideration.

 

Although there had been cases where the authorities had removed drugs from the insurance benefit list according to the revocation of licenses, the authorities’ preemptive and voluntary action to change and amend the prescription guidelines is very rare, to the extent that actual cases of such examples are difficult to find.

 

This is interpreted as the health authorities’ determination to take a step closer to advancing regulatory science for public health and prioritizing the patient’s safety in drug intake in line with the vision set by the FDA, the authority that is considered the international standard for drug approval and regulations.

 

Recently, the MFDS had issued a Dear Healthcare Professional Letter regarding the safety of JAK inhibitors such as Pfizer’s ‘Xeljanz (tofacitinib),’ Lilly's ‘Olumiant (baricitinib),’ ‘Abbvie’s ‘Rinvoq PR Tab (Upadacitinib),’ etc.

 

The MFDS’ measure was made after reviewing the results of the FDA’s randomized, large-scale clinical trial on the safety of ‘tofacitinib’ that was released on the 1st.

 

The FDA had announced that tofacitinib increased the risk of serious heart-related events such as heart attack, stroke, cancer, blood clots, and death.

 

The drug that is receiving particular interest among the JAK inhibitors is Pfizer’s Xeljanz, which had already had a safety issue in 2019 in addition to the heart attack risk that was discussed this time.

 

Xeljanz is an oral JAK inhibitor indicated for rheumatoid arthritis and ulcerative colitis.

 

After discussions with Pfizer, the FDA had ▲changed the ulcerative colitis indication from first-line to second-line and ▲added warnings to refrain from prescribing the drug to patients at risk of embolisms, at the time of issue development.

 

On why the health authorities have made such prompt measures to address the issue of JAK inhibitors is considered to be because this is the second time the safety issue of the JAK inhibitor Xeljanz rose in 3 years with concerns for two side effects - increased risk of heart attacks and the 'risk of embolism.'.

 

The prospect is that the academic society will show neutral or tacit consent to the authorities' move to amend the other reimbursement standards after changing the scope of approval.

 

As in the FDA’s case of restricting Xeljanz's indication from first-line to second-line, where academic societies abroad made changes to the prescription guidelines after taking a neutral stance in respect to the opinions set by the regulatory authorities, rather than showing strong consent.

 

If the Korean health authorities and academia reach a consensus on changing the indication for JAK inhibitors from 1st line to 2nd line treatment, the market for injectable traditional biopharmaceuticals is highly likely to expand.

 

The current market established for JAK inhibitors is around ₩30 billion, and the prescription market for biologics such as Humira, Remicade, Simponi, Mabthera, Actemra, Cosentyx, Kynteles, and Stelara is around ₩350 billion annually.