Where is it located?
Nelson Vergel is Seeking Input: Tell the FDA to Stop Attacking Compounded Hormones
- Thread starter Nelson Vergel
- Start date
Where is it located?
Are we talking years, do you think?
7601 North Sam Houston Pkwy W #100, Houston, TX 77064
It's a few miles north of where they were before, along the same highway.
Nelson Vergel
Founder, ExcelMale.com
I am not sure. I would not be surprised if it takes two years.
We are a 503B compounding pharmacy located in Oklahoma and have been manufacturing hormone pellets for years. Recently began production of Testosterone Cypionate 200 mg/ml available in 2 ml or 10 ml vials. We CANNOT make HCG due to being restricted by the FDA and anyone that does so without a Biologics license is doing to illegally.
madman
Super Moderator
Updated April 25, 2023
Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
503B Category 1: Bulk Drug Substances Under Evaluation (see pdf)
** Designates bulk drug substances that are components of FDA-approved drugs
• Anastrazole**
• DHEA (dehydroepiandrosterone) **
• Dutasteride **
• Estradiol**
• Estriol
• Estrone**
• Finasteride**
• Isotretinoin**
• Minoxidil**
• Nandrolone Decanoate**
• Progesterone**
• Testosterone**
• Testosterone Cypionate**
• Testosterone Enanthate**
• Testosterone Propionate**
• Tretinoin**
503B Category 2: Bulk Drug Substances that Raise Significant Safety Risks
• Ibutamoren Mesylate (MK-677)
Nelson Vergel
Founder, ExcelMale.com
I wonder how they determined that ibutamoren has significant health risks. It is now approved for pediatric use in kids with growth retardation who need a GH stimulation test.
madman
Super Moderator
Content Current as of 12/29/2022
Safety Risks Associated with Certain Bulk Drug Substances Nominated...
Category 2 of the Bulk Substances Nominated Under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act
Summary of the Safety Risks
Category 2 substance | Nominated with sufficient information under 503A or 503B or both | Date added to Category 2 | Safety risks |
|---|
MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study - PubMed
Most elderly patients admitted for hip fracture suffer functional decline. Previous studies with MK-0677 in hip fracture patients suggested possible benefits to functional recovery. This is a randomized, double-blind study of 123 elderly hip fracture patients assigned to receive 25mg/day of...
pubmed.ncbi.nlm.nih.gov
What a joke!
This sums it up.
*Merck began searching for a nonpeptide mimetic that had a high oral bioavailability and pharmacokinetics that would allow for once-daily oral administration. 14 A breakthrough occurred when L-692,429 was discovered as it showed that it was possible to design a small molecule peptidomimetic agonist for GHRP6. 14 While this molecule had an improved oral bioavailability, the pharmacokinetic properties did not allow for a once-daily oral administration. 14 Continued modifications led to the development of L-163,191 which was shown to have “excellent potency, selectivity, and oral bioavailability, as well as appropriate pharmacokinetics suitable for once daily oral dosing” and with continued research found “to have an excellent safety profile.”14 This led to the clinical development of L-163,191 as MK-0677, or ibutamoren mesylate. 9,14
Ibutamoren mesylate: Summary Report
archive.hshsl.umaryland.edu
Ibutamoren mesylate: Summary Report
INTRODUCTION
This report was created to assist the Food and Drug Administration (FDA) in their evaluation of the use of ibutamoren mesylate (also known as MK-0677 or MK-677) (UNII code: GJ0EGN38UL) which was nominated for use as a bulk drug substance in compounding by outsourcing facilities under section 503B of the Federal Food, Drug, and Cosmetic Act.
The aim of this report was to describe how ibutamoren mesylate is used in clinical research and practice to diagnose, prevent, or treat disease. Due to the broad, exploratory nature of this aim, scoping review methodology was used. Following the scoping review framework, a systematic literature review was conducted and healthcare practitioners were consulted to identify how ibutamoren mesylate has been used historically and currently. 1-3 Assessment of study quality and risk of bias were not performed because the aim of this report was not to make specific recommendations on the use of this substance in clinical practice.1,4,5 Rather, the aim was to summarize the available evidence on the use of ibutamoren mesylate and thereby assist the FDA to determine whether there is a need for the inclusion of this substance on the 503B Bulks List
CURRENT AND HISTORIC USE
Results of background information
• Ibutamoren mesylate is not available as an FDA-approved product in the nominated dosage form and ROA.
• Ibutamoren mesylate is not available as an OTC product in the US.
• There is no current United States Pharmacopeia (USP) monograph for ibutamoren mesylate.
• Ibutamoren mesylate is not available in the nominated dosage form and ROA in any of the foreign registries searched.
Use of ibutamoren mesylate:
Three hundred ten patients received ibutamoren mesylate as an experimental treatment for bone formation and resorption, administered orally in doses ranging from 5 mg to 50 mg. Duration of treatment ranged from 14 days to 18 months.
Two hundred eighty-two patients received ibutamoren mesylate as an experimental treatment for Alzheimer’s disease, administered orally at a dose of 25 mg. Duration of treatment was 12 months.
One hundred forty-six patients received ibutamoren mesylate as an experimental treatment for posthip fracture surgery, administered orally at a dose of 25 mg. Duration of treatment was 6 months.
Sixty-two patients received ibutamoren mesylate as an experimental treatment to prevent the decline in fat-free mass and to decrease abdominal visceral fat, administered orally at a dose of 25 mg. Duration of treatment ranged from 1 to 2 years.
Twenty-two patients received ibutamoren mesylate as an experimental treatment to improve nutritional status in end-stage renal disease (ESRD), administered orally at a dose of 25 mg. Duration of treatment was 3 months.
Twenty-two patients received ibutamoren mesylate as an experimental treatment for use in older adults, administered orally in doses ranging from 2 mg to 25 mg. Duration of treatment was 42 days.
An unknown number of hypogonadal men on testosterone therapy received ibutamoren mesylate for reduction of body fat mass and increase in skeletal muscle mass at an unknown dose and duration of treatment.
Eighteen patients received ibutamoren mesylate as an experimental treatment in children with GHD, administered orally in doses ranging from 0.2 mg/kg/day to 0.8 mg/kg/day. Duration of treatment was 15 days.
Fifteen patients received ibutamoren mesylate as an experimental treatment to improve sleep quality, administered orally at a dose ranging from 2 mg to 25 mg. Duration of treatment ranged from 21 days to 28 days.
Twelve patients received ibutamoren mesylate as an experimental treatment for use in obese patients, administered orally at a dose of 25 mg. Duration of treatment was 8 weeks. 10
Eight patients received ibutamoren mesylate as an experimental treatment to reverse the catabolic response to dietary energy restriction, administered orally at a dose of 25 mg. Duration of treatment was 28 days.
Five patients received ibutamoren mesylate as an experimental treatment in adults with GH deficiency, administered orally in doses ranging from 10 mg to 50 mg. Duration of treatment was 8 days.
Refer to Tables 6 and 7 for summaries of dosage by indication.
Ibutamoren was not used as a compounded product, nor was it used in a combination product.
In 12 studies, the authors concluded that further studies were necessary for the use of ibutamoren mesylate in the treatment of GHD of childhood-onset, to increase bone mass and reduce risk of fractures, to improve nutritional status in patients with ESRD, to promote a reduction in body fat in obese patients, to decrease LDL-C concentrations, in the treatment of conditions associated with GHD in older adults, to prevent the decline in fat-free mass and to decrease abdominal visceral fat, in the rehabilitation of patients post-hip fracture, in the treatment of catabolic patients secondary to acute or chronic disease states, and to improve sleep quality. In 3 studies, the authors’ concluding statement did not provide a recommendation regarding use of ibutamoren mesylate to promote bone formation and resorption and to modify body composition and total body fat. In 2 studies, the authors’ concluding statement did not recommend the use of ibutamoren mesylate to improve overall physical functional performance in patients post-hip fracture surgery and to slow the rate of progression of Alzheimer’s disease.
Pharmacology and historical use
Several studies were identified that did not meet the inclusion criteria but provided valuable information about the pharmacology and historical use of ibutamoren mesylate.
Growth hormone (GH), also known as somatotropin, is a protein that is produced by the somatotroph cells found in the anterior lobe of the pituitary gland. GH receptors are found throughout the body and are responsible for many metabolic functions including promoting growth in children, increasing lipolysis, stimulating protein synthesis, and antagonizing insulin.9 GH is regulated by 3 hypothalamic hormones: growth hormone-releasing hormone (GHRH), somatostatin, and ghrelin.11 GHRH and ghrelin stimulate GH release while somatostatin inhibits release. 11 GH has a pulsatile secretion with production occurring primarily at night and pulses following exercise, trauma, and sleep.9 GH production rises in childhood with the peak occurring at puberty and then declines with age. As GH declines with age, exogenous administration has many proposed benefits including increasing lean muscle mass, decreasing fat mass, increasing exercise tolerance, and increasing muscle strength.9 However, due to potential safety concerns associated with supratherapeutic GH levels resulting from the bypass of the normal, regulatory feedback, there has been an interest in the use of GH secretagogues.9,12
GH secretagogues include GH-releasing peptides (GHRPs), like GHRP2 and GHRP6, and GHRH analogs, like sermorelin. GH secretagogues stimulate the endogenous secretion of GH, GHRPs increase the number of somatotrophs releasing GH, and GHRH analogs increase the amount of GH secreted, which maintains levels within normal physiologic levels.9,13 The action of GHRPs is independent of GHRH so as a result, when a GHRH analog and a GHRP are used together they have a synergistic effect stimulating the release of GH.9,12 11
GHRPs were first synthesized in 1977 and GHRP6 was the first that was found to have significant in vivo activity; however, due to its poor oral bioavailability and short half-life, it had to be administered frequently and as an injection.9 Additionally, “as a peptide it did not lend itself to the optimization of pharmacokinetic properties”. 14 Due to these challenges, using GHRP6 as a model structure, Merck began searching for a nonpeptide mimetic that had a high oral bioavailability and pharmacokinetics that would allow for once-daily oral administration. 14 A breakthrough occurred when L-692,429 was discovered as it showed that it was possible to design a small molecule peptidomimetic agonist for GHRP6. 14 While this molecule had an improved oral bioavailability, the pharmacokinetic properties did not allow for a once-daily oral administration. 14 Continued modifications led to the development of L-163,191 which was shown to have “excellent potency, selectivity, and oral bioavailability, as well as appropriate pharmacokinetics suitable for once daily oral dosing” and with continued research found “to have an excellent safety profile.”14 This led to the clinical development of L-163,191 as MK-0677, or ibutamoren mesylate. 9,14
Ibutamoren mesylate binds to the ghrelin receptor and was found to not only enhance the pulsatile release of GH but also act as an antagonist to somatostatin allowing for GH levels to remain elevated for up to 360 minutes after a single oral dose.13,15 In 1996, Chapman et al studied the effects of 2 mg, 10 mg, and 25 mg of MK-677 administered orally once daily compared to placebo in 32 healthy adults between the ages of 64-81 years. 16 Patients were randomized to receive either MK-677 or placebo; GH and IGF-1, a surrogate blood marker for GH, levels were measured. After 2 weeks, GH and IGF-1 levels in the 10 mg and 25 mg MK-677 groups were significantly increased compared at baseline in a dose-dependent manner; participants that received 25 mg of MK-677 had IGF-1 levels restored to normal levels seen in young adults. Additionally, it was found that the GH increase was due to enhanced pulsatile GH secretion and not an increase in the number of pulses. This was the first study to show that daily administration of a GH secretagogue could increase GH and IGF-1 levels in older adults.16
Copinschi et al evaluated the use of 5 mg and 25 mg of MK-677 compared to placebo in 9 healthy males between the ages of 18-30 years to evaluate the effect on pulsatile GH secretion, IGF-1 levels, and adrenocortical function. 17 Additionally, the medication was taken at night to determine whether it would enhance the physiological release of GH that occurs at night.17 The study found that the amount of GH secreted was similar in all 3 groups; however, in the MK-677 groups, the number of GH pulses was increased. IGF-1 levels were also increased, in a dose-dependent manner, in the MK677 groups compared to placebo. This study concluded that the use of “MK-677 for the treatment of relative somatotrophic deficiency, particular in older adults compromised by such deficiency, deserves further investigation.”17
Several studies were conducted evaluating the use of ibutamoren mesylate in various disease states and Merck was developing the drug for FDA approval for use in GH deficient children, recovery of hip fractures, and to treat the frail elderly; however, Merck discontinued its development in 1999. 18 After Merck discontinued development, Ammonett Pharma LLC continued to develop MK-0677 for treatment of GHDin children and in 2017 received a designated orphan status from FDA for treatment of GHD. 19 In 2018, Lumos Pharma, Inc acquired the license for MK-0677 from Ammonett Pharma LLC, renamed it LUM-201, and is currently developing it for treatment of pediatric GHD, Turner Syndrome, and children born small for gestational age (SGA).20 Lumos Pharma, Inc is currently recruiting participants for a multi-national, phase 2 study of LUM-201 in pediatric GHD (the OraGrowtH210 Trial) with expected results in mid-2022. 20,21
CONCLUSION
Ibutamoren mesylate was nominated for inclusion on the 503B Bulks List as an oral capsule to treat GHD and catabolic conditions. Ibutamoren mesylate is not available in the nominated dosage forms and ROA in any of the national medical registries searched.
From the literature review, ibutamoren mesylate has been studied to treat GHD as well as use in various conditions associated with declining GH levels, including post-hip fracture surgery to facilitate the rehabilitation process, to improve anthropomorphic parameters, to improve the nutritional status in patients with ESRD, to promote bone formation and resorption, Alzheimer’s disease, to improve sleep quality, to reverse the catabolic response to dietary energy restrictions, and use in obese patients. All of the studies utilized ibutamoren mesylate as a once-daily product with doses ranging from 2 mg to 50 mg. None of the authors’ recommended the routine use of ibutamoren mesylate, however, several studies reported positive preliminary results concluding that additional studies are warranted. Ibutamoren mesylate has a designated orphan drug status for treatment of GHD and is currently being developed by Lumos Pharma, Inc under then name LUM-201. Lumos Pharma, Inc is currently recruiting participants for a multi-national, phase 2 study of LUM-201 in pediatric GHD (the OraGrowtH210 Trial) with expected results in mid-2022.
From the interviews conducted, only 2 SMEs were familiar with ibutamoren mesylate. However, a third SME stated that there would be a need for it in catabolic conditions if it worked. Ibutamoren was being developed by Merck, but after 20 years of research, they decided to close the program. Recent interest has led to ibutamoren being developed for use in children with GHD and one SME hoped that it will be approved for use in children in the next 2-3 years. Ibutamoren mesylate is also used as a “lifestyle medication” for patients that want to “feel better” and “try to mitigate muscle loss.” Since it was being developed by Merck, there is a lot of initial clinical trial data “showing that it can be very beneficial” and outline a clear dosing regimen. The 2 SMEs that were familiar with ibutamoren mesylated differed in their opinions on compounding ibutamoren. One SME stated that while it is a “fantastic drug” and is “pretty safe,” since the API is not available did not see any way that it could be compounded. The other SME said that since GH secretagogues, including ibutamoren mesylate, are not currently approved for use the only way to obtain them is through a compounding pharmacy.
Zero people responded to the survey distributed via professional medical associations and available on the project website.
Attachments
testiculus
Active Member
I wondered what the impact of being categorized in one of these categories is, so I looked up the regulations. The net of it is as follows:
Category 1: Not on the approved list, but the FDA won't take any enforcement actions if they are compounded. FDA is evaluating and may one day add to the approved list.
Category 2 & 3: Cannot be compounded, unless it is an FDA approved drug and is on the FDA drug shortage list.
This is effectively a ban on ibutamoren from compounding pharmacies. Doesn't look like there is any end in sight for the FDA's war against compounding pharmacies. I guess they figure it's better for everybody to get things from the black market rather than being under the care of a physician and a well run pharmacy.
Category 1: Not on the approved list, but the FDA won't take any enforcement actions if they are compounded. FDA is evaluating and may one day add to the approved list.
Category 2 & 3: Cannot be compounded, unless it is an FDA approved drug and is on the FDA drug shortage list.
This is effectively a ban on ibutamoren from compounding pharmacies. Doesn't look like there is any end in sight for the FDA's war against compounding pharmacies. I guess they figure it's better for everybody to get things from the black market rather than being under the care of a physician and a well run pharmacy.
Systemlord
Member
Cardiac drugs generate outrageous profits for pharmaceutical interests. Pharmaceutical companies face huge losses if too many Americans use natural hormones to reduce their reliance on expensive prescription drugs.
To be honest, the entire federal government and all health care related investigative agencies have a super negative attitude towards compounding pharmacies. This is due to fraudulent compounding pharmacy schemes from 2013 till now. Medicare, Medicaid, Tricare lost billions in compounding pharmacy schemes that involved provider kickbacks.
Unfortunately, they don't see the positive side of honest compounding pharmacies that provide competition to major pharmaceutical companies. I've never once heard a compounding pharmacy mentioned in a positive light. The FDA definitely falls in this category
Unfortunately, they don't see the positive side of honest compounding pharmacies that provide competition to major pharmaceutical companies. I've never once heard a compounding pharmacy mentioned in a positive light. The FDA definitely falls in this category
T
tareload
Guest
Excellent summary. What do you think happens once all these go to Cat 2?
Lights out. Putting the frog on a light simmer. Slowly turn on the heat.
madman
Super Moderator
Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List
Additions to Category 1:
• Gonadorelin acetate
The following substance will be added to Category 2 because FDA has identified significant safety risks for this substance:
• Ipamorelin acetate
503B Category 1: Bulk Drug Substances Under Evaluation (see pdf)
** Designates bulk drug substances that are components of FDA-approved drugs
• Anastrazole**
• DHEA (dehydroepiandrosterone) **
• Dutasteride **
• Estradiol**
• Estradiol Cypionate**
• Estriol
• Estrone**
• Finasteride**
• Isotretinoin**
• Minoxidil**
• Nandrolone Decanoate**
• Progesterone**
• Testosterone**
• Testosterone Cypionate**
• Testosterone Enanthate**
• Testosterone Propionate**
• Tretinoin**
503B Category 2: Bulk Drug Substances that Raise Significant Safety Risks
• GHRP-2 (for injectable and nasal routes of administration)
• GHRP-6
• Ibutamoren Mesylate (MK-677)
• Ipamorelin Acetate
madman
Super Moderator
Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (9/2023)
503A Category 1: Bulk Drug Substances Under Evaluation (see pdf)
• 7 Keto Dehydroepiandrosterone
• Enclomiphene Citrate
• Pregnenolone
503A Category 2: Bulk Drug Substances that Raise Significant Safety Risks
• BPC-157
• Ibutamoren Mesylate
• Ipamorelin Acetate
• Kisspeptin-10
• Melanotan II
503A Category 3: Bulk Drug Substances Nominated Without Adequate Support
• GHRP-2
• GHRP-6
503A Category 1: Bulk Drug Substances Under Evaluation (see pdf)
• 7 Keto Dehydroepiandrosterone
• Enclomiphene Citrate
• Pregnenolone
503A Category 2: Bulk Drug Substances that Raise Significant Safety Risks
• BPC-157
• Ibutamoren Mesylate
• Ipamorelin Acetate
• Kisspeptin-10
• Melanotan II
503A Category 3: Bulk Drug Substances Nominated Without Adequate Support
• GHRP-2
• GHRP-6
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