Pfizer Inc. (NYSE:PFE) and Eli Lilly and Company (NYSE:LLY) announced today that they are preparing to resume the Phase 3 clinical program for tanezumab.
In the prior clinical studies of more than 11,000 patients, tanezumab demonstrated clinically meaningful efficacy vs. placebo and other select commonly used pain medicines.
I wonder what other “select commonly used pain medicines” it was tested against, when “commonly used” includes everything from aspirin and Tylenol to oxycodone.
WIthout knowing exactly what other medicines and at what doses this “new and improved” pain medication was trialed against, there’s no way to know if this is going to be helpful.
A partial clinical hold has been in place for tanezumab and all other anti-nerve growth factor antibodies since December 2012 due to adverse changes in the sympathetic nervous system of mature animals. Studies in terminal cancer pain were allowed to proceed.
Tanezumab is a humanized monoclonal antibody that selectively targets nerve growth factor (NGF), a regulator of pain processing and sensitivity.
NGF levels increase as a result of injury or inflammation and in chronic pain states.
The sentence makes it sound like the rise of NGF levels is a problem, when NGF is actually a critical piece of a feedback loop that controls inflammation:
There is growing interest in the complex relationship between the nervous and immune systems and how its alteration can affect homeostasis and result in the development of inflammatory diseases.
A key mediator in cross-talk between the two systems is nerve growth factor (NGF), which can influence both neuronal cell function and immune cell activity.
NGF has a variety of effects that can be either pro-inflammatory or anti-inflammatory.
This apparent contradiction can be explained by considering NGF as part of an endogenous mechanism that, while activating immune responses, also activates pathways necessary to dampen the inflammatory response and limit tissue damage.
Tanezumab selectively binds to NGF, thereby inhibiting this protein from activating pain-signaling neurons.
I have grave concerns about this new class of potential pain relievers that inhibit the actions of “Nerve Growth Factor (NGF)”. When I looked it up, it sounded very beneficial:
The article goes on to list many positive effects of high levels of NGF and problems found when the levels are too low:
- Nerve growth factor prevents or reduces neuronal degeneration in animal models of neurodegenerative diseases and these encouraging results in animals have led to several clinical trials in humans.
- NGF promotes peripheral nerve regeneration in rats.
- NGF appears to promote myelin repair. Hence NGF may be useful for the treatment of multiple sclerosis.
- Dysregulation of NGF signaling has also been linked to Alzheimer’s disease.
cells genetically engineered to synthesize and secrete NGF and implanted in patients’ basal forebrains reliably pumped out NGF, which enhanced the cells’ size and their ability to sprout new neural fibers.
The treatment also rescued vulnerable cells, even if they already showed the trademark signs of Alzheimer’s pathology. In some patients, these beneficial effects lasted almost 10 years after the treatment. Even patients who died responded positively to the therapy.
- Neurotrophins, including NGF, have been shown to affect many areas of the brain, including areas that are related to Rett syndrome, bipolar disorder, and Alzheimer’s disease. Stress and/or anxiety are usually a precipitating factor in these disorders and affects levels of NGF, leading to impaired cognitive functioning. This impaired cognitive functioning can be seen in patients with Schizophrenia.
- higher NGF levels from the atypical antipsychotic medications lead to a reduction in negative symptoms of Schizophrenia.
- NGF has been shown to restore learning ability in rats recovering from induced alcoholism
- NGF has also been shown to accelerate wound healing.
- Impairment of neuroplasticity and altered levels of neuro-trophins are involved in bipolar disorder. NGF has been found to be decreased overall in bipolar disorder patients.
When bipolar disorder patientswere treated with lithium, their NGF concentrations increased in the frontal cortex, limbic forebrain, hippocampus, and amygdala
- Also, NGF has been shown to play a role in a number cardiovascular diseases, such as coronary atherosclerosis, obesity, type 2 diabetes, and metabolic syndrome. Reduced plasma levels of NGF and BDNF have been associated with acute coronary syndromes and metabolic syndromes.
- Nerve growth factor may contribute to increased longevity and mental capacity
So this is a long list of reasons to question the use of anti-NGF drugs, even if NGFs are part of a process that results in pain.
I worry that over-enthusiastic approval due to its non-opioid status could force it upon us before damages are well-known.
If anyone knows why anti-NGF drugs wouldn’t be extremely detrimental to our minds and bodies, please let me know – seriously!