HIP hip hoOrAy

n just 24 months we may know if we have the allusive Holy Grail for a real solution for a serious disease that has never had a safe and durable solution for a lot of people. We know it won't help everyone, but for millions the answer might be a resounding Grail type find in iPPS..Tonight let's take a look at a subset of OA, specifically OA in the hip joint.

In this post we will cover Hip OA, what is it, how prevalent is it? We'll then cover the progression of OA. We'll take a look at the projected rates of the final stage of OA and finally we will relate it back to us.

As always, please do enjoy.



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Hip OA generally progresses slowly, it might start off with niggling pain and then increase gradually over time.Sometimes the pain can be felt at the back, sometimes the pain can be felt through to the thighs. As time goes on pain levels can increase. Things that were taken for granted such as getting out of a car or even getting up from a couch can all start to cause discomfort. Sleeping at night with pain can lead to a disrupted sleep pattern causing further problems like stress and tiredness. 'Sleep at Night' incidentally was rated as the highest category for iPPS providing relief and benefit in the latest results of the EAP program last year.



_{Sleeping at night was the highest mean reduction in terms of WOMAC pain in the recent EAP program.}



It depends on what kind of OA you have, if it's back and hip, generally things like power walking on hard surfaces will aggravate it. If it's more like osteoporosis then weight bearing exercise can often help. Low impact exercises are usually recommended and start slowly. Always see your doc or registered practitioner for further advice. Check out this video which clearly gives us an idea of what some of the problems are involving Hip OA and how it manifests itself. Simply click on the below hyperlink, it only goes for one minute 45 seconds... well worth a look to get a clearer understanding of the hip joint and the damage that can take place.


HIP OA VIDEO









While the numbers are big all over, take a look at just the UK for instance.In the UK it's the fastest growing cause of disability affecting around 10% of the population. There are some 8.5 million people that are affected and it accounts for some one third of "chronic moderate to severe pain in the UK" ².



_{Hmmm take care of those British hips...the stats aren't great.}


In relation to HIP OA it is the second most common large joint affected by OA, In 2011 alone there were some 80,000 hip replacements in the UK due to OA. The estimated cost of Total Hip Replacement in the UK was £426 Million which is a huge 66% increase in costs over the prior decade. Serous disease affecting serious numbers of people in the UK. You know what, there will be no extra waiting time for iPPS in Britain, we are tackling the EMA at the same time as the huge US market..when we start...we are going to start with the biggest bang ever.







Paradigmers, while researching for this one I came across this statement : "It is likely that in the early stages, damage to the cartilage might be completely reversible, thanks to the healing capacities of the lesions, especially in the very young." ³ However, once these lesions take hold, it gets harder for the body to repair them.

Enter iPPS.

iPPS can have the capacity to allow more time for the body to heal while it holds inflammation back (my views). Sure we will test this theory a lot more in the upcoming trials and studies. The rate of OA development varies, and by a lot, in different people. In some it will lay dormant for years before causing more symptoms...in others within 12 to 24 months it will lead to destruction and pain. The moral of this one, like a number of disease and conditions of the body, is to address it early.







Whether it be due to injury or wear and tear, at first there is no real difference in the thickness of cartilage and everything would look normal in X-rays. However there will be some degree of debris and degradative enzymes at play. This action will eventually become irritating to the joints. The body then compensates by increasing the amount of synovial fluid to counteract and dilute the irritating debris and lubricate the damaged joint.

It gets to a point such as in Andrew Walker's case where the fluid is too much and needs to be drained.As OA progresses the lesions left untreated, worsen. It is here where iPPS can work its magic, addressing these lesions. Dr Felson has already shown this link to be strong, between the presence of these lesions, OA and of course, pain. If not addressed then the cartilage begins to weaken, and deplete...the slow healing process that needs to be employed is missed and cannot complete properly. "The evolution is thus a succession of painful flare-ups separated by an intervals of variable durations, up to the stage of cartilage ulceration".³

It has been shown that by resting the joint during such flare ups there is a chance of healing as the cartilage regains its firm surface. Again it is in this area that iPPS buys some time...enough time for the inflammation to subside and the body's healing processes can more steadily get to work. As I have said before, I believe this is just one of the ways iPPS helps. I also suspect there is a more proactive role that it plays not only by simply buying this time for healing but also via some more direct involvement whether it be through the down regulation of NGF, a disruption of some or many of these cytokine developments and an interference via cellular interactions of the glucose based molecule. (My views).

The takeaway here is that we know that an interval of rest can be very helpful for OA sufferers, this is just one of the clues that the body can heal itself but needs the time and ability to do so. Holding back the flood waters of inflammation is just one of the major ways iPPS works its magic in order to assist in this process.




_{Like a massive dam, holding back the inflammatory pressures....}


Often these intervals of pain may not always be pronounced so people neglect to address their OA with the subsequent risk of it only really being discovered and escalated when the damage has really been done.As other posters have mentioned here at HC, particularly if you are in an industry like professional sports, jobs that entail additional structural joint load or you have already had some major injury in the recent past, it might be prudent to consider iPPS as a preventative measure once approved and once more information is known?

Remember, a stat I posted a while ago, some 50% of all sporting injuries can lead to OA within ten years.⁴ A further statistic from the same reference: "It has been shown that more than 80% of American football players with a history of knee injury had evidence of OA 10 to 30 years after competing."







The final stage of OA is of course to have surgery, usually not a great options but it can give relief to many. There is some evidence that it will not work for all and that in cases pain and inflammation still persist. Paradigmers, I don't know out of every 100 patients that eventually take on iPPS, how many of them will avoid TKA and THA...We have anecdotal evidence from not only PAR but from a few patients that iPPS at least in some cases have managed to delay and even avoid surgery. Even for that matter Andrew Walker is another example of having avoiding full knee replacement.

But what I can give you is a real sense of what numbers of operations have happened and are predicted to occur without an intervention such as iPPS....Take a look at the following info:Figure 1 shows the cumulative estimated operations from 2020 to 2040. Figure 2 depicts quite graphically, the rate at which these operations are expected to increase over the next few years in just the USA.










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Wait a minute Mozz...we are doing the Big P3 trial (002 and 003) on Knee OA...why would they do a separate study on Hip OA?Good question 99*... why do this?




_{* Reference of 99 is a Get Smart (1965-1970) reference whereby the hero, Maxwell Smart always was happy to take on questions by his attractive understudy, Agent 99.}

Well if one keeps the end points quite separate and the sponsor keeps it all separate then this sort of factorial trial (PARA010) is possible.



_{Para 010 Hip Trial - Magnificent, another trial, another data set, another addition to potentially broaden our label.}



Each study is of course statistically powered in it's own right and there should be no crossover.Ok so in my opinion this actually makes a whole heap of sense. Why? Well a number of reasons:


1) The additional effort/overhead to incorporate a study at this stage isn't too much extra effort. Well specially compared to doing a full on P3 on it completely separate to the main trials. You might as well do this in parallel, anyway you have the CRO's lined up, patient recruiting should be fairly smooth by the time they are ready for this study and they can line up a lot of the same clinics, clinicians, labs and observers anyway.

2) The data can be added to the overall database and potentially contribute towards the overall dossier and act as further supporting evidence for the read out of the main trial....one could quote "our drug does this for Knee OA and as an added benefit it performs this well with Hip OA too" as an example.

3) Ok so another big advantage is if the read out for Hip OA is in line with knee, (and why wouldn't it be?) then it will broaden the official label. What's the advantage/meaning of that? Well imagine the Doc's...they no longer have to chance it to some extent by prescribing Zilosul for a HIP OA patient...they can do it officially as the study has been shown to work in the area of the Hip Joint. Two major joints having successful studies done gives the Docs confidence that it isn't just a trial and error thing. They can officially prescribe it with the blessing of the FDA...the EMA...and the TGA....this now multiples not only our revenue potential and addressable market....BUT it gets us there in a shorter time.

Hip OA is the second most prevalent joint disease. It affects millions and is approximately 65% of the numbers of Knee OA. It's forecasted to grow over the next few years and there is only one real solution that I can see on the upcoming market thats a safe and potentially viable solution, first in line, best in class....actually, there is no one else currently in the class.



_{One solution in the class? That's us!}




Yes a slow journey it is....yes boring at times......but when this drought one day breaks....it'll be one heck of a positive flow .....my views.







1] https://www.arthritis-health.com/types/osteoarthritis/hip-osteoarthritis-symptoms-and-signs
2] https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/leeds-osteoarthritis-hip-cohort/
3] https://www.arthrolink.com/en/disease/knowing/evolution-osteoarthritis
4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039183/#:~:text=Such%20joint%20injuries%20may%20cause,cartilage%2C%20even%20with%20normal%20use.&text=Ligament%20injuries%20and%20meniscal%20tears,with%20pain%20and%20functional%20impairment.