Saphnelo: New FDA-approved drug for lupus?

Most (70%) of systemic lupus erythematosus (SLE) patients have high levels of interferons
Interferons cause inflammation of organs, leading to permanent organ damage
Anifrolumab competes with interferon by attaching to the attachments (receptors) on immune system cells
Normally, when interferons bind to those receptors, the immune system cells become more active
Then they alert more immune system cells to become more active and attack body organs
Anifrolumab decreases this cascade of events from happening
This leads to less inflammation
It is a biologic monoclonal antibody, so it will be expensive!

Anifrolumab (Saphnelo) works differently than any drug used in the past to treat lupus!
1st in its class! With it aimed at a major cause of lupus (high type-1 interferon levels), it should be the next FDA-approved drug for lupus. 

​Saphnelo, the next FDA-approved drug to treat lupus: How is it given?

Saphnelo is given intravenously (IV), 300 mg, every 4 weeks (I suspect it will be 300 mg)

What were the research results?
There was a 90% reduction of interferons at 6 months in the patients who started off with high levels
Other labs measuring lupus inflammation improved (anti-dsDNA, C3, C4, CH50)
Low white blood cell counts and low platelet counts improved

What other good things did it do for the SLE patients?

They had less disease activity
Even patients who started with normal interferon levels overall improved
In TULIP-2: 57% (46 placebo vs 72 anifrolumab patients) more patients who started with high interferon levels met the primary endpoint with anifrolumab
… 58% more patients! Impressive!
When looking at all patients, a 51% higher number of patients responded to anifrolumab, including those with normal interferon levels!
You do not have to have high interferon levels to respond!
Close to twice as many patients were able to decrease their steroids to goal (25 placebo vs 45 on anifrolumab)
Lower steroids is important because higher doses of steroids cause organ damage
Anifrolumab reduced lupus flares

It especially worked well for cutaneous lupus

Look at the picture above from one of the studies
This patient had an amazing improvement. Many others did just as well
They measured skin activity with a CLASI score and looked for more than a 50% improvement
CLASI stands for Cutaneous Lupus Erythematosus Disease Area and Severity Index

Twice as many anifrolumab patients responded: No wonder Saphnelo is the next FDA-approved drug to treat lupus

     -The numbers were 25% of the placebo cutaneous lupus patients responded, while 49% on anifrolumab did 

How fast does it work?

Reduced disease activity was seen as early as 2 months

What were the side effects of anifrolumab

When comparing side effects, it is important to know that the placebo patients were not truly “placebo”
They were receiving standard of care therapy
In other words, most were on immunosuppressants and steroids that cause side effects themselves
The patients on anifrolumab were also on immunosuppressants and steroids
Therefore sorting out what anifrolumab may do vs the other drugs is very difficult

But, here are the numbers (combination of three different anifrolumab research studies):

Around 87% of anifrolumab patients and 80% of placebo patients had side effects
This include nuisance, mild side effects
The most common were viral upper respiratory tract (URI) and throat infections (cold-like infections)
Infusion reactions were the other most common
For example, 10% of the placebo (standard of care) patients had URIs, 18% on anifrolumab did
This is not surprising, interferon is important for fighting viral infections
Shingles occurred in around 6% of anifrolumab patients and 1%-2% of placebo patients
Again, not surprising since shingles is due to chicken pox virus
(MAKE SURE TO GET A SHINGLES VACCINE, SUCH AS SHINGRIX, BEFORE TREATMENT!)
6% of anifrolumab patients had to stop treatment due to side effects; 3% of placebo patients had to stop

What patients were not studied?

Patients with severe kidney inflammation (lupus nephritis, LN), brain, and nerve lupus (neuropsychiatric) were not
Therefore, we do not know if it works in them
However, I will go out on a limb and predict it will help LN patients
We know that interferon plays a role in LN
Just because we do not have study results for severe LN patients, this does not mean it does not work

What could possibly keep the FDA from approving it?

In the first TULIP-1 trial, it did not meet its primary endpoint (research goal called the SRI-4)
This could get some voting members to vote “no” for approval
However, lupus experts realize how hard it is to prove that lupus drugs work
They evaluated how the drug performed in the 1st trial
Patients did have significant improvements
They were able to lower their steroids and there was marked improvements in cutaneous lupus
One criticism is that some patients changed their NSAID (like ibuprofen) during the study
These patients were automatically labeled as a drug failure, though many of them had great responses
So they changed the primary endpoint for TULIP-2 based on their analysis of TULIP-1
The TULIP-2 trial did meet its primary end point

Bottom lines- Saphnelo, the next FDA-approved drug to treat lupus:

– Impressive results, especially for skin lupus
– Low rate of side effects (colds, sore throats, infusion reactions, shingles are the most important)
– Get your Shingrix shot before treatment
– I have a list of SLE patients who have failed everything who need to try this drug if it is FDA-approved!

As of August 2, 2021, anifrolumab became the next FDA-approved drug for lupus!

Good luck to AstraZeneca who is the manufacturer of Saphnelo