and OA is more prevalent than one might realise. But I have to hand it to PAR, they are acutely aware of what iPPS can do for this infliction and although they have chosen to pursue the knee joint first, the hip and certainly hand in association with other joints are well on their radar for further avenues of success.
Please now, do enjoy.
INTRODUCTION
Hand OA typically starts with a slight pain every now and again in one of the many joints of the hand. It, over time, may change from a dull pain to something more sharper. As it progresses, it may even wake you up at night and as it finally progresses, a patient may lose the ability to even open and close their fingers completely.1
CAUSATION?
Usually hand OA occurs later in life. Several factors can influence it's onset and indeed it's progression:
Age: the older you are, the more likely you are to have hand OA.
Sex: women are more likely to be affected than men.
Race: whites are more often affected than African Americans.
Weight: obese people are more likely to have hand OA than thinner people.
Genes: some people inherit the tendency to develop osteoarthritis, usually at a younger age.
Injuries: Even when properly treated, an injured joint is more likely to develop OA over time. Fractures and dislocations are among the most common injuries that lead to arthritis.
Joint issues: Joint infections, overuse, loose ligaments, and poorly aligned joints can also lead to hand or wrist arthritis.
Wait a sec Mozz, Obese people? They don't walk on their hands? How are they more susceptible to developing OA?
It has been found that due to low-grade inflammation this makes your joints more likely to develop OA. In fact, the factors of risk of getting hand OA go something like this:
"Compared to normal-weight subjects, being overweight or obese increased the risk of OA at all three sites, especially at the knee: overweight and (grade I, II) obesity increased knee OA risk by a factor of 2, 3.1 and 4.7 fold respectively". 3
Of course, there can be a number of other factors that lead to OA of the hand, some include heredity aspects, injuries, overuse and even malalignment of joints.
Mozz Note: Malalignment is one of the biggest causes of OA. Valgus is defined as a deformity involving oblique displacement of part of a limb away from the midline.
The below excerpt from the world famous Dr D Felson, a past consultant to Paradigm. Yes, that was a Paul R. coup. The engineers/mathematicians amongst us will know that 3 degrees ain't a lot...
PREVALENCE
Hand OA is quite prevalent.
Take a look at this next fact:
"The incidence of hand OA increased from 371.30 million in 1990 to 676.02 million in 2019, increasing by 82.07%".4
And another fact:
"About half of all women and one-quarter of all men will experience the stiffness and pain of osteoarthritis (OA) of the hands by the time they are 85 years old. A degenerative disease that affects all the tissues of a joint, OA leads to the breakdown over time of the smooth, protective cartilage on the ends of bones, so bones rub together, causing pain. The 29 bones of your hands and wrists come together to form many small joints that can be affected by OA".5
With some 29 bones in your hands, well that's a lot of areas that can be susceptible to OA.
What can go wrong? What can cause pain? A lot!
So how does one address hand OA currently?
Well the usual culprits of course...NSAIDS is the big one...injections intra articularly which are usually the use of corticosteroids. However, be warned, there is at least some evidence of rapid joint failure.. With some 29 bones in just our one hand, this makes for a very delicate shot!
The beauty of this SubQ administered molecule is that it is systemic. You do not have to carefully inject it. In fact you have the injection no where near the hand, typically! It's in the fatty layers such as thighs, stomach or butt for example. It makes its way to the areas of concern, systemically.
FURTHER EVIDENCE
Yeah but Mozz, when can we learn about iPPS's specific data on hand OA itself?
(Gee you guys don't want much). For that we need a dedicated well controlled study right? We will have to wait for that one, right?
Wrong.
We already have had it.
What? Where?
We first saw this evidence from PAR's own Ross River Study, it was a double blinded placebo controlled study. n was low, just 20 patients.6
Results? Take a read:
"PPS was well tolerated, with a similar proportion of subjects reporting at least one treatment-emergent adverse event (TEAE) in the treatment and placebo groups. Injection site reactions were the most common TEAE and occurred more frequently in the PPS group. Dominant hand grip strength and SF-36 scores improved with PPS at all time points assessed, with hand grip strength improvement of 6.99 kg (p = 0.0189) higher than placebo at Day 15. PPS showed significant improvements versus placebo in adjusted mean relative change from baseline for RAPID3 Pain (p = 0.0197) and Total (p = 0.0101) scores at Day 15. At the conclusion of the study overall joint symptoms, assessed by RAPID3, showed near remission in 61.5% of PPS subjects versus 14.3% of placebo subjects. Additionally, PPS treatment improved COMP, CTX-II, CCL1, CXCL12, CXCL16 and CCL17 biomarker levels versus placebo".
Wow, there is a fair bit to unpack in those results above.
Let's do that now:
1) Ahh safety, it's all about safety...iPPS was well tolerated, a good start!
2) Hand grip strength improvement in active bet placebo and was statistically significant (0.0189) despite n being just 20 ! This statement translates to an excellent drug effect size.
3) All of these great results didn't come after months, it came within just 15 days - we see separation between the cohorts.
4) This next one is music to me eyes: "NEAR REMISSION" in some 61.5% in the PPS group compared to a mere 14.3% in Placebo.
...what about a Mozz bonus then...yeah go on...
5) COMP, and the magnificent, most prognostic of OA markers, CTXII, improved.
Are YOU new to Mozz?
New to PAR?
New to iPPS?
Here is a refresher just for you!
COMP
Comp is a biomarker that has been said to be one of the most diagnostic markers of OA. You elevate your COMP levels in the blood from baseline and surely your cartilage is being lost. I have to give credit where it is due, it was David Hunter that stated: "Among subjects with symptomatic knee OA, a single measurement of increased COMP predicted subsequent cartilage loss on MRI1".5.5
In fact, so great this marker is, "For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times".5.5
Do we have any evidence of iPPS specifically on COMP?
Mate:
"Cartilage degradation measured by the detection of Cartilage Oligomeric Matrix Protein (COMP) in serum showed a mean percentage reduction of 11.9% from baseline at Day 1 to Day 53 in the iPPS treatment group in contrast to a mean percentage increase of 2.1% in placebo".11
So in other words, Placebo went BACKWARDS by 2.1%...iPPS resulted in an almost 12% improvement. Remember, slowing down COMP measurements equates directly to less degradation of that precious cartilage.
CTXII
Here is one of the most prognostic of markers in OA. "...urinary CTX-II, a matrix metalloproteinase (MMP)-derived type II collagen fragment, is currently the most promising biological OA marker, which has been evaluated in a variety of clinical studies. It has been associated with the presence, incidence and progression of OA and with bone marrow lesions, the extent of the osteophytes and the level of pain". 5.6
New guys, fyi - there is a Biomarker consortium specifically charged by the FDA to identify biomarkers of OA.5.7 This consortium is lead by Virginia K and David H.
Getting back to the RRV data, take a read of this extract as announced by PAR:
QUALITY OF LIFE
Quality of Life, Assessment of Daily Living (ADL), PGIC, these are all concepts that have become important to the regulatory agencies, how did iPPS rate in this domain?
Again, take a look:
Overall, the patients in the active PPS group felt significantly better than their compadres in the Placebo group. At follow up at 12 weeks, 72.7% (8/11) subjects in the iPPS group showed near remission in contrast to 14.3% (1/7) subjects in the placebo group.
It's easy to forget with such strong data, the n was so low.
As I have said in the past, I long for our final results from 012 (Phase 3) where the numbers are magnified (n = 466). Now that will be quite a read.
DON'T HOLD BACK
So last week I posted a summary on the 1999 paper by the amazing Dr P Ghosh. I held something back in that post deliberately for this here post on Hand OA. Let's investigate:
A study on oral PPS was conducted and some hand OA observations were noted:
"These data strongly suggest that multiple courses of treatment with CaPPS may be more effective in providing symptomatic relief than a single loading dose. From this study, Verbruggen et al (360)concluded that CaPPS at 20 mg/kg produced symptomatic relief in patients with OA of the hands for up to 6 weeks after cessation of treatment without any apparent side effects".6
Remember, that was a study utilising Oral PPS, not the SubQ version. New guys? The SubQ has a much more pronounced bioavailability (uptake), the performance is better, the results are more profound, the MOA extent is different.
CONCLUSION
Hand OA is a scaled problem affecting millions. It is a difficult one to treat as you can't easily just inject intra-articularly. iPPS indeed to the rescue and the initial results are looking pretty good.
While researching for this post I came across this relatively recent update on the prevalence of OA generally (Not just Hand OA) in the prestigious The Lancet.7
Look at the markets where we may enter into initially (Green arrows):
For those that have hand pain, try iPPS, hopefully after that, it results in better hand grip strength, a better night's sleep and the ability to do this, without pain:
- Mozz
Yes, still better to DYOR, just because I like this stock and I like our prospects, it does NOT equate to a NO risk proposition.
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and OA is more prevalent than one might realise. But I have to hand it to PAR, they are acutely aware of what iPPS can do for this infliction and although they have chosen to pursue the knee joint first, the hip and certainly hand in association with other joints are well on their radar for further avenues of success.
(20min delay)