I have
been quite surprised to read this morning about fulranumab in knee and hip
osteoarthritis. Rheumatology Network referred to a study on fulranomab in osteoarthritis pain [1]. Fulranomab is a monoclonal antibody that selectively targets
nerve growth factor (NGF). It targets NGF like tanezumab [2], on which we didn’t
hear much after the US FDA had imposed a partial clinical hold on studies due
to unexpected adverse events. The point had been osteonecrosis [ON], but later
this serious adverse event had been “downgraded” to rapid progression
osteoarthritis [3]: “Despite initial reports, tanezumab
treatment was not associated with an increase in ON but was associated with an
increase in RPOA [rapid progression osteoarthritis].”
But let’s
come to the study by P. Sanga and colleagues [4]: “Long-Term Safety and
Efficacy of Fulranumab in Patients With Moderate-to-Severe Osteoarthritis Pain:
A Phase II Randomized, Double-Blind, Placebo-Controlled Extension Study”. The
authors concluded: “Long-term treatment with fulranumab was generally
well-tolerated and efficacious. RPOA was observed as a safety signal. Future
studies are warranted to demonstrate whether the risk of RPOA can be reduced in
patients taking fulranumab.” We talk about a phase II double-blind,
placebo-controlled extension study of 401 patients. “Overall, 81 joint
replacements were performed in 71 patients (8 [11%] receiving placebo and 63
[89%] receiving fulranumab); 15 patients (21%) had rapid progression of OA (RPOA).”
I don’t read this as “long-term treatment with fulranumab was generally
well-tolerated and efficacious.” I read the results as if you receive
fulranumab you have a higher chance for joint replacement. Maybe one of the
authors could clarify this discrepancy.
I have a
problem with MABs like tanezumab, fasinumab or fulranumab in osteoarthritis as pain and
not reversing the course of osteoarthritis is addressed.
Adisinsight
noted as most recent event: “24 Jun 2016 Takeda
terminates its licence for fulranumab in Japan” (25 Mar 2017) [5].
John
Carroll had written an article last year: “That blockbuster anti-NGF pain drug
fulranumab? J&J doesn't want it anymore” [6]. Last year J&J had decided
to hand back fulranumab to Amgen. The reason given: “This decision was based on
strategic portfolio prioritization and was not based on any emerging safety
concerns from the Phase 3 clinical studies with fulranumab”. I can understand
this very well.
If we
look at fulranumab, we should also look at tanezumab and fasinumab. A metaanalysis
for tanezumab has been punblished by Shun-Li Kan and colleagues last year [7].
Conclusion: “Tanezumab can alleviate pain and improve function for patients
with OA of the knee. However, considering the limited number of studies, this
conclusion should be interpreted cautiously and more clinical randomized
controlled trials are needed to verify the efficacy and safety of tanezumab for
OA of the knee.” Last year “the FDA (U.S. Food and Drug Administration) had
placed the Phase 2 study for fasinumab for the indication of osteoarthritis
pain and chronic back pain on clinical hold” [8].
One unmet
need for the treatment of osteoarthritis is a safe and effective pain
medication. I don’t see this need being met by anti-NGF-MABs like furanumab,
tanezumab or fasinumab. Moreover these drugs do not seem to lead to a better
course of osteoarthritis degenerating joints.
Links:
.
No comments:
Post a Comment