Hypopara Conference 2023 Highlights

The Hypopara Conference took place virtually and in person on November 3-4 2023. All recordings and additional conference information can be found on the Hypopara Association’s (HPA) website www.hypopara.org

Disclaimer: I’m not a medical professional and these notes are incomplete, are referenced as highlights, and are my own observations. I am not affiliated with the HPA or any Pharma company. I take these notes for family and friends who are unable to attend but want to know more information. Visit hypopara.org to watch conference videos and speak to your doctor before making any changes.

The Task Force Paper a one-stop-shop on the management of hypopara for medical professionals. This paper has information about both surgical and non-surgical hypopara, quality of life, treatments, testing, recommendations, and surgical practices to prevent hypopara. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4691


If hospital doctors aren’t listening by Dr Christofides:

If you struggle to have someone listen to a care plan when you go to the ER, try saying you’re a seizure risk and bring an advocate if possible. This may help them take you seriously.

In a hospital setting, a nurse is your best advocate. If you can’t get a nurse to help, call the patient care manager for the hospital.

The hospital operator knows that number. Call them and ask for patient manager or nurse manager. (“Make sure to send them a thank you/cookies when you’re discharged”)

For doctors dismissing symptoms, try explaining what’s going to happen if the symptoms continue, it just naming the symptom. Instead of saying “throat tightness”, tell providers “my throat is tightening and it’s getting harder to breath and my larynx is going to spasm and soon I won’t be able to speak.”

Or “My muscle spasms are so bad, I’m afraid to drive in case I get into an accident because I swerve or miss the brake or I’m afraid to hold my child in case I drop them” (several patients confirmed they’ve had this experience)

Every phone has an emergency/ medical ID app. Use it.

Also wear a bracelet and keep something in your car too in case your wallet or purse is unavailable.

On your phone wallpaper, you can use an app called LockScreen to add info on every lock screen.

(My lockscreen has my name, hypopara/calcium dependent. See medical bracelet. Transcon PTH EAP Clinical Trial, and emergency contact)

Hypopara can cause muscles to spasm locally, even if calcium serum levels are in range. (Which is why your foot can spasm when you’re driving for a long time)

Question: since fasting causes hypocalcemia, how should patients prep for a fasting surgery?

Answer: Best surgery prep is to go into the hospital the night before so you can be monitored and have quick intervention when needed

Current hypopara trials require patients to drop off their current treatment for 30-60 days which is unethical. This was ruled as unethical for the rest of endocrine, but not for hypopara. FDA upholds the law and they must be lobbied to change this. The Hypopara Association will be advocating for this on March 5.


Dr Rubin presenting Cognitive function in hypopara:

Depression is one of the most common complications. Most hypopara patients also have anxiety.

Transcon data shows patients had improvement in both cognitive and physical symptoms improved. There’s very little quantifiable measures in the research for cognitive function. How do we see this in a scientific method?

Cognitive domains to include in study

  • vocabulary
  • level of reading
  • cognitive control and coordination (like executive function)
  • semantic fluency (finding words)
  • attention (focusing on relevant info)
  • processing speed
  • visuo-spatial functioning
  • memory
  • episodic memory
  • working memory
  • visual memory
  • auditory memory

Post-surgical hypopara patients had worse:

  • Visuo-spacial
  • Attention
  • Executive function
  • Semantic memory

I’m not allowed to share the slide with the results of the study vs general pop. People on PTH replacement did better. However, in some cases, even on replacement PTH (like Transcon PTH) most hypopara patients still didn’t reach “healthy people” levels of cognitive function.

There’s a wide variability in cognitive function. Why? Does brain calcification cause the cognitive function difference? They are researching this.

Speculation: PTH may promote blood flow to brain 

The majority of people with the disease are white, post menopausal women, which makes diverse studies more difficult. There’s also often thyroid symptoms that cause an additional cognitive burden. Estrogen lowers calcium levels, which is why periods can affect calcium levels and cognitive symptoms = 

Columbia University is doing a study:

SHINE study (study of hypothyroidism and its natural evolution)

To learn about the long-term complications of hypoparathyroidism, including kidney, brain, vascular and bone complications. Any type of hypopara and any type of disease management. It’s once a year trip to NYC to do testing. Contact Dr. Rubin to learn more. They’re looking for 40 more patients


ENCALERET (BridgeBio) update:

Session 1:

Super excited to hear an update about Encalerent, which is an oral drug in clinical trial for treatment of genetic ADH1 Hypopara. They’re in Phase 2B trials right now. People with ADH1 have normally functioning parathyroid glands, but are getting a wrong signal. This drug helps correct that signal. Study results on 13 patients are showing positive results over 18 months.

They are going to attempt to treat post-surgical hypopara patients with Encaleret. They are enrolling up to 15 people, up to 10 people who have been hypopara for greater than one year and up to five who have only been Hypopara for under a year.

Session 2:

Update from Dr. Scott about Bridgebio/Calcylytix which is an ADH1 genetic hypopara treatment named Encaleret.

Causes of hypoparathyroidism:

Post surgical 70 to 80% of cases
Genetic is 10 to 12.5% of cases
Auto immune is less than 10% of cases
Unknown/idiopathic is less than 10% of cases

We are aware of 26 different genes that when they have a change could cause genetic hypoparathyroidism. DetectHypopara is a generic testing program and Dr. Mannstadt presented results of patients tested earlier this year at a conference.

ADH1 is the most common non-surgical hypopara cause. ADH1 is caused by changes in the gene for the calcium sensing receptor. It tricks the body into thinking the calcium levels are normal when they are too low.

Encaleret normalizes the calcium sensing receptors. It’s in Phase 2 study.

CLARIFY STUDY: disease, monitoring study, presentation, and progression of ADH1

CALIBRATE STUDY: understanding effects Encaleret on blood and urine calcium

2023: Proof of concept, study and post surgical hypoparathyroidism

2024: Pediatric study


Dr Mannstadt Kidney Health in Hypopara

Risks in for kidneys with hypopara:

  • Kidney stones
  • Nephrocalcinosis
  • Impaired functions
  • Kidneys produce hormones that are important for blood pressure, active vitamin D, erythropoietin for red blood cells
  • Hypercalciuria = too much calcium inurine. This is a problem with hypopara.

If there’s no parathyroid hormone, no one tells the kidney to keep the calcium inside the body. That’s why there’s a lot of calcium in the urine. There’s not really a “threshold” but generally the guidelines are <250mg women and <300mg men

The central challenge in the management of hypoparathyroidism is that if the calcium is normal for the population, it’s too high for people not on PTH therapy because it leads to hypercalcuria.

This is why on conventional therapy (active D + calcium) it’s recommended that patient stay on the low end or just below normal.

Hypopara is a risk factors for kidney stones.

Nephrocalcinosis: calcium salts within the renal tissue

Impaired kidney functions (CKD = chronic kidney disease).

CKD risk factors include diabetes, blood pressure, older kidneys generally don’t work as well. Nephrocalcinosis is probably a risk factor but hasn’t been studied widely

The better the glomerular filtration rate (GFR), the healthier the kidneys are.

Normal is 90 or above
Mild is 60 to 89 (mL/min/1.73 m2)
Moderate is 30 to 59
Severe is 15 to 29
End stage renal diseases under 15

Kidney health-what you can do:

  • Try to keep serum calcium around the low limit of normal. High enough to avoid major symptoms, low enough to protect your kidneys.
  • Divide your calcium intake throughout the day to prevent significant fluctuations and calcium levels.
  • Timing of serum calcium lab check. As discussed yesterday, morning before your meds is best, but consistency is key. Even better if you can get multiple times during the day regularly so you know your highest and lowest expected value.
  • Check your 24 Hour urinary calcium excretion.
  • Can also measure stone profile of urine
  • Nuts and chocolate can cause kidney stones.

Dr Wang from Virginia Common Wealth University on CALCIUM TESTERS!

Trying to devise a self-measurement device for calcium

Money is obviously the problem and they’re looking for fundraising ideas.

The question: A variety of at-home glucose meters have been available for the last few decades. Where are the at-home calcium meters?

History:

  • First home has glucometer was introduced 1981
  • 1967 the ionophore-based calcium electrode
  • In 1985, commercial calcium electrode introduced in hospital setting
  • 1991 ISTAT handheld calcium analyzer for hospital use . ISTAT is not approved for home use

No improvement in calcium testing since then.

“Calcium sensor is far behind and nobody cares” – Dr. Wang

Calcium meter is harder to develop than glucose sensors. (I can’t share the slides, but basically calcium range doesn’t have a baseline, has a narrower range, and the acceptable error rate is so much smaller. Acceptable error rate: <5% for calcium. Glucose can tolerate an error rate of 20%)

Their research on how to design identical sensors: the first ion-selective electrode with a baseline.

They have started with potassium, since it’s easier to detect than calcium. They released a proof of concept paper, and an international patent application was filed, using potassium as an example.

It has the potential to become a subcutaneous continuous monitor, but this will take several more years of fundamental research. They will also need additional funding.

He’s explained two different sensors they’ve been studying.

The first, an inkjet sensor, failed.

The second one, an oil-based liquid sensor using a color-metric response, seems extremely promising.

Combining the blood with the sample creates a colored liquid which equates to a blood measurement of calcium (from blue to green to yellow)

  • Plan for new grant 1-2 years
  • Find a new industry partner to manufacture prototypes

He promised to post updates on his website for us to follow along


Update on Eneboparatide (Amolyt Pharma)

Phase 3 Calypso trial

Technical issues with the live feed, missed the beginning of the session

This drug is PTH-RP, which a different drug formulation than NATPARA (1-84), Transcon PTH (1-34), or Forteo (1-34)

* Important note: Eneboparatide clinical trial requires 3 month wash out period to join

Patients were able to discontinue active vitamin D (calcitriol), within two weeks of treatment initiation.

Patients were able to reduce oral calcium supplementation to below 500 mg.

Calcium levels in the blood were maintained (although lower than what I’d classify as normal levels? I’m confused by this slide). Normalized urine calcium rapidly and sustained normalization

Bone safety: Treatment with eneboparatide induced a gradual and mild increase in both anabolic and catabolic bone markers to the mid-normal level by 4-8 weeks (aka: except to see stable bones and bone turnover)

Trial notes:

  • No serious, adverse events reported in trials.
  • Phase 3 trial has started.
  • Study sites are international: 63 sites selected (14 countries)
  • Requires 3 month washout period between current treatment and beginning study.

Q&A notes:

  • Would expect to see lower phosphorus levels
  • Have not done deep assessment on impact of drug on quality of life. But early data is encouraging, and they expect to see a substantial improvement
  • Why does there needs to be a washout period? (Remember yesterday’s discussion that this was ruled unethical in other endocrine diseases two years ago). Amolyt said they Need to be able to isolate the effect and they want people to be stable during the “run-in period”

Kent Hawryluk, president of MBX biosciences (clinical stage biopharma company)

Company partner is Dr. Richard DiMarchi who is a leader in endo research, including on Forteo. Also did big things in diabetes.

MBX was founded in 2019 and focused on treating rare endocrine diseases. The lead program in hypopara is transitioning from phase 1 to phase 2 trials.

This session has heavy science language, but the summary is they’re working on an ONCE WEEKLY “prodrug” injection called MBX2109

It chemically converts at a precisely controlled rate to active drug once injected. Clinical proof of concept has been established. Safe and well tolerated with repeat administration. After 3 to 4 weekly injections, patients were stabilized.

MBX2109 is designated as an orphan drug. Phase 2 trial called AVAIL will start after an FDA meeting. They will let HPA know when trial opens. They will have global trials.

Danette (a hypopara patient and part of the HPA) joined MBX for the hypopara study.

Q: Will there be a washout period (between medications)?

A: They need to discuss this with the FDA, but they’ve heard the patient response to washout periods and how much of a problem that is. Washout periods are dictated by the FDA. The HPA is working on fighting that law.


Rare X Database

Deb Murphy from HPA Board is speaking about it

Rare X is a database for patient communities. While drug companies have their own collected data, we don’t-as a hypopara community-have a data collection system to share with researchers (Demark has shared data and this has helped with medical care development)

  • Patients/caregivers own & manage their data
  • Compare your patient’s progress against others
  • If eligible, you may have the chance to participate in clinical trials
  • Reach more researchers worldwide – more eyes on data
  • Ability to connect with other patient organizations
  • Ability to update symptom changes at any time
  • Ability to manage who uses your data
  • Faster treatment development

Started this program in June of last year. The goal is to make this an international project. Join and share data at: Hypoparathyroidism.rare-x.org

Questions, contact rarexsupport@globalgenes.org


Ask The Doctor Panel highlights:

* DO NOT TAKE WELLBUTRIN IF YOU HAVE HYPOPARA! There’s an issue with seizure threshold

  • Increasing calcium vs increasing calcitriol: Many doctors have different opinions. US prefers more calcium, Europe prefers more calcitriol. Depends on patient and their calcium intake. Patients with high phosphate levels, increase calcium. Calcium helps bind and eliminate phosphate.

     

  • How much food should you take with calcium? You want to take calcium with food to bind the phosphate in the food with the calcium. This will protect the kidneys by eliminating phosphate (Remember hypopara means you can’t control the phosphate levels)
  • You want your Vitamin D levels to be 30 or above even on PTH therapy
  • The doctors keep saying you should be taking 600-1200mg of calcium a day because of health…even if patient has stable in-range calcium level. (As a patient, I recommend you talk to your doctor bc you don’t want to go hypercalcemic)
  • 6-8% of neck surgeries end in permanent hypopara/hypocalcemia. Transient hypopara is like 30ish% and usually resolves.
  • Are any of the PTH drugs safe during pregnancy? No. Do not start a drug if you’re planning to become pregnant. However, pregnancy can cause hypopara to be more mild in some patients. It’s very important to make a plan with your medical team for both your and the baby’s safety
  • Lauren’s Hope can help you write your medical bracelet tag LaurensHope.com
  • Confirmed: flying does lower calcium because of changes in CO2
  • Transcon PTH and the results. It can actually REVERSE kidney damage

Visit the new hypopara association website! You can recommend and research endos, insurance terms, and clinical trials, etc. website: hypopara.org

I’ll share any more updates on events or news on my blog at HeatherNovak.net/Hypopara

To learn more about my journey with Transcon PTH: HeatherNovak.net/Transcon

That concludes the 2023 Hypopara Conference!

Personal note: I didn’t see anyone wearing a mask at this conference, which was surprising. The dangers of covid on Hypopara https://www.ese-hormones.org/media/4422/ese-insight-2022_v6-web.pdf

Disclaimer: I’m not a medical professional and these notes are incomplete and are my own observations. Visit hypopara.org to watch conference videos and speak to your doctor before making any changes.

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Marie
Marie
8 months ago

Awesome notes. I didn’t see contact information for Dr. Rubin.