Endocrine research remains at the forefront of medical breakthroughs, which has led to cutting-edge treatment options, therapies, and products. From remarkable new treatments for acromegaly, thyroid eye disease, hypoglycemia, and diabetes to new devices aimed at glucose monitoring in adults and children, a mail-in semen analysis kit, and much more, Endocrine News takes a closer look at some of these new innovations announced throughout 2021.
Another year down. Another year where pretty much everything was still impacted by the COVID-19 pandemic, but another year where endocrine researchers and clinicians continued to remain at the forefront of medical research, the result of which been a variety of breakthroughs that not only address new treatment options, therapies, and products, but health disparities and equity as well.
A New Treatment for Hypoparathyroidism
In January, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation (ODD) to AZP-3601, Amolyt Pharma’s clinical candidate for the treatment of hypoparathyroidism.
AZP-3601 is a therapeutic peptide designed to target a specific configuration of the parathyroid hormone (PTH) receptor in order to safely produce sustained levels of calcium in the blood and thereby manage the symptoms of hypoparathyroidism. The selective action of AZP-3601 through this distinct configuration of the PTH receptor is also intended to limit urine calcium excretion by stimulating calcium reabsorption by the kidney, consequently preventing chronic kidney disease. In addition, the receptor profile and short half-life of AZP-3601 are expected to preserve bone integrity, an important benefit since the majority of patients with hypoparathyroidism are middle-aged women often at increased risk of osteoporosis.
“We believe the FDA’s granting of Orphan Drug Designation to AZP-3601 reflects the agency’s recognition that new and more effective treatment options are needed for this serious endocrine disorder,” says Endocrine Society member Thierry Abribat, PhD, chief executive officer of Amolyt Pharma. “We are pleased to have recently dosed the first subject in our Phase 1 clinical trial, and we are committed to executing an efficient development program to diligently bring this promising therapeutic to patients.”
Male Fertility Test Kit Via Mail
That same month, the journal Fertility and Sterility published a paper on the development and validation of the Fellow kit, for mail-in semen analysis. The study was led by James Smith, director of Male Reproductive Health in the Urology Department at University of California San Francisco, a team of clinicians from the University of Southern California, Yale, and Hackensack Medical Center, and in partnership with the male reproductive sciences company, Fellow Health.
After comparing hundreds of semen samples in a clinical trial, researchers found the mail-in Fellow test provided the same accuracy as semen samples analyzed within 1 hour of generation.
UCSF was the first health system in the U.S. to offer the Fellow kit. “This mail-in system offers men easy access to high quality semen analysis from the comfort of their homes,” says Smith. “The at-home option is valuable as people forgo doctor office visits to limit their exposure to COVID-19.”
Positive Data for Acromegaly Treatment
During ENDO 2021, Chiasma announced positive clinical data from its MPOWERED™ Phase 3 trial of MYCAPSSA. The data from MPOWERED showed that MYCAPSSA improved clinical symptoms and other patient-reported outcomes compared to long-acting injectable somatostatin receptor ligands (iSRLs) in patients with acromegaly. In addition, MYCAPSSA met the pre-specified non-inferiority margin compared to long-acting iSRLs in maintenance of biochemical response.
“The new encouraging data from all five late-breaking poster presentations further expand our understanding of oral octreotide capsules’ potential positive impact for patients with acromegaly who would otherwise need monthly, frequently burdensome SRLs injections,” says Society member Maria Fleseriu, MD, FACE, lead investigator of the MPOWERED study, professor of Medicine and Neurological Surgery, director of the Pituitary Center at Oregon Health and Science University in Portland, Oregon, and immediate past president of the Pituitary Society. “As a practicing endocrinologist, I believe that these data provide valuable insights to physicians on the potential benefit of a twice daily oral drug versus long-acting injections for most patients.”
New Severe Hypoglycemia Treatment for People with Diabetes
Zealand Pharma in March announced that the FDA approved Zegalogue® (dasiglucagon) injection for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes aged 6 years and above.
The FDA approval was based on efficacy results from three randomized, double-blind, placebo-controlled multicenter Phase 3 studies of Zegalogue in children aged 6 to 17 and in adults with type 1 diabetes. The primary efficacy endpoint for all three studies was time to plasma glucose recovery (treatment success), defined as an increase in blood glucose of ≥20 mg/dL from time of administration, without additional intervention within 45 minutes. The primary endpoint was successfully achieved across the adult and pediatric studies with a significantly faster median time to blood glucose recovery of only 10 minutes following Zegalogue administration compared to 30-45 minutes placebo. In the main Phase 3 adult trial 99% of patients recovered within 15 minutes.
In these studies, the most common adverse events reported (≥2%) were nausea, vomiting, headache, diarrhea, and injection site pain in adults; and nausea, vomiting, headache, and injection site pain in pediatrics.
Racial, Gender, and Socioeconomic Factors Could Impede Proper Diabetes Care
Researchers at the Perelman School of Medicine at the University of Pennsylvania found significant disparities in the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of drugs proven to treat type 2 diabetes, with usage remaining low with Black, Asian, and lower-income groups despite an increase in overall usage for patients with type 2 diabetes. The study is published in JAMA Network Open.
“Study after study, including large randomized trials, have demonstrated a cardio-protective and kidney-protective effect of this class of medications” says the study’s lead author, Lauren Eberly, MD, MPH, a cardiology fellow at the University of Pennsylvania. “We know there are already higher rates of heart failure and kidney disease among Black patients. What is concerning is that this is a therapy we know prevents death from those conditions and prevents progression from those conditions, and yet, we found that Black patients are less likely to get this therapy, as well as female patients and those with lower socioeconomic status.”
In this study, researchers examined data from October 2015 to June 2019 from more than 900,000 diverse, commercially insured patients with type 2 diabetes and found that the cumulative percentage of patients treated with SGLT2 inhibitors increased from 3.8 percent to 11.9 percent. However, the analyses showed that Black, Asian, and female patients had lower rates of SGLT2 inhibitor use, as well as patients whose median household income was less than $50,000. The study also found that usage rates remained low for patients with heart failure, cardiovascular disease, and chronic kidney disease.
“These results are consistent with prior studies that have shown decreased use of novel therapies among Black patients. Implementation strategies that prioritize not only delivery of guideline-directed care but also equitableguideline-directed care are critical in ensuring all patients have access to evidence-based therapies” says the study’s senior author, Srinath Adusumalli, MD, MSHP an assistant professor of Clinical Medicine in the Division of Cardiovascular Medicine.
The study found that having a visit with an endocrinologist in the last 12 months was one of the strongest factors associated with SGLT2 inhibitor use, acknowledging that the demonstrated clinical benefit may not be common knowledge yet for many non-specialist providers treating patients with diabetes. Additionally, marginalized patient groups likely have barriers to accessing specialty care. Eberly and her fellow researchers encourage the development of strategies to increase the comfort of all providers, especially primary care and cardiology providers, with prescribing this class of drugs.
“If left unaddressed, these inequities in utilization will continue to widen well-documented disparities in cardiovascular and kidney outcomes in the U.S.” Eberly says.
TEPEZZA Improves TED Outcomes
Horizon Therapeutics in April published pooled data from the TEPEZZA® (teprotumumab-trbw) Phase 2 and Phase 3 clinical trials in The Lancet Diabetes & Endocrinology. The data further reinforce that TEPEZZA significantly improves proptosis and diplopia for patients with thyroid eye disease (TED) in different subgroups, with most maintaining a long-term response. TEPEZZA is a fully human monoclonal antibody (mAb) and a targeted inhibitor of the insulin-like growth factor-1 receptor (IGF-1R).
“This integrated analysis comprises one of the largest controlled study populations reported to date in people living with thyroid eye disease, which allowed us to evaluate a variety of patient subgroups, including those whose symptoms were considered more severe,” says Society member George Kahaly, MD, PhD, professor of medicine and endocrinology and metabolism at Johannes Gutenberg University Medical Center in Mainz, Germany, and primary author of the paper. “Of most importance, the data clearly show that TEPEZZA mitigates varying levels of disease severity, including proptosis and diplopia, which are the most progressive and difficult findings to treat, and that improvements continue for the long term.”
In this report, treatment study outcomes and follow-up off-treatment data were integrated from two 24-week multicenter, double-masked, placebo-controlled clinical trials where patients were randomized to receive TEPEZZA (n=84) or placebo (n=87) once every three weeks for a total of eight infusions. The final treatment study visit was at Week 24, which was three weeks after the final infusion. Responses were also evaluated at seven weeks and 51 weeks after the final dose of TEPEZZA. Responses were analyzed for proptosis and diplopia, as well as a post-hoc analysis of a combined outcome measure: the “ophthalmic composite outcome.” The composite outcome is calculated as the percentage of patients with clinical improvement in one eye in at least two of the following: 1) proptosis, 2) diplopia, 3) eyelid swelling, 4) lid aperture, 5) globe motility, and 6) Clinical Activity Score, without deterioration of at least two of these outcomes in either eye.
New Study Findings
- There was no evidence for acute disease rebound (increase in percentage of patients no longer meeting proptosis, diplopia or ophthalmic composite outcome) seven weeks after the last dose of TEPEZZA.
- Proptosis (87 percent; 62/71), diplopia (66 percent; 38/58) and ophthalmic composite outcome (92 percent; 66/72) responses were observed seven weeks after the last dose of TEPEZZA.
- A post-hoc analysis of the composite ophthalmic outcome indicated that 81 percent (68/84) of TEPEZZA patients versus 44 percent (38/87) of placebo patients were responders at Week 24.
- Proptosis (67 percent; 38/57), diplopia (69 percent; 33/48) and composite outcome response (83 percent; 48/58) were observed 51 weeks after the last dose of TEPEZZA for those who had long-term off-treatment data available.
Real-World Data on Over 4,000 Patients Using the Medtronic MiniMed™ 780G System Demonstrate Time in Range
Medtronic in June announced real-world clinical outcomes for 4,120 individuals on its MiniMed™ 780G system, a small subset of those on the system across nine countries in Europe. Data showed an average overall Time in Range of 76.2% and an overnight Time in Range of 83%. From an experience perspective, users remained in Advanced Hybrid Closed Loop (AHCL) mode, also referred to as the SmartGuard™ algorithm, for an average of 94% of the time, and an overall reduction in interactions required with the system demonstrated a more seamless experience than previous insulin pump systems. This data was presented at the 14th annual international conference onAdvanced Technologies & Treatments for Diabetes (ATTD).
“It is extremely encouraging to see Medtronic advancing both clinical outcomes as well as the user experience through their latest MiniMed 780G system. It is clear that learnings from the launch of the world’s first hybrid closed loop informed the design of this next-generation system,” says Society member Chantal Mathieu, MD, PhD, an endocrinologist at University Hospitals Leuven-KULeuven, Belgium. “We know that no two individuals with type 1 diabetes are the same, and that life gets in the way of managing diabetes perfectly. I am confident in this system’s ability to do what a person with diabetes may not be able to do on their own by helping them minimize highs and lows, and ultimately live their lives less burdened by their diabetes.”
The advanced SmartGuard algorithm in the MiniMed 780G system automates and personalizes the delivery of basal insulin by adjusting every five minutes, 24 hours a day. The latest system also includes an advanced algorithm that automatically corrects highs every five minutes through autocorrection dosing, in addition to protecting against lows. Autocorrection dosing is designed to correct highs that may result from not logging a meal, logging a meal late, or underestimating the carbohydrate content of the meal.
The MiniMed 780G system is currently approved for the treatment of type 1 diabetes in people age 7 to 80 years. The system enables the personalization of glucose goals with an adjustable target setting as low as 100 mg/dL (5.5 mmol/L) — lower than any other insulin pump system. The MiniMed 780G system is now available in 30 countries across Europe, the Middle East and Africa, and is currently being reviewed by the Food and Drug Administration (FDA) for approval in the U.S.
The real-world performance analysis aggregated information from individuals who uploaded their data to CareLink™ Personal from August 27, 2020 to March 3, 2021. A large majority of real-world users studied are achieving glycemic goals shared by major diabetes professional organizations, including:
- 79% of individuals had a Glucose Management Indicator (GMI) less than 7%, which mirrors the average A1C level that would be expected based on mean glucose.
- 77.3% of individuals had a Time in Range above 70%.
- 74.1% of individuals achieved both, a GMI less than 7% and a Time in Range above 70%.
In addition to the data reported from the overall cohort of 4,120 individuals, a smaller cohort of 812 individuals was analyzed, to compare the difference in outcomes as individuals move from pre-AHCL initiation (also referred to as open loop) to post-AHCL initiation. Within that cohort, individuals experienced an average Time in Range increase of 12.1% (from 63.4% to 75.5%), a 15.7 mg/dL or 0.9 mmol/L drop in mean sensor glucose (from 162.2 mg/dL to 146.5 mg/dL or 9.0 mmol/L to 8.1 mmol/L), and a 0.4% drop in GMI (from 7.2% to 6.8%) post AHCL initiation.
Dexcom Publishes Two Studies Focusing on Clinical Outcomes of CGM in More Diverse Populations
Dexcom also presented two new studies during the 14th International Conference on Advanced Technologies & Treatments for Diabetes, focusing on clinical outcomes of CGM use in broader and more diverse populations and new data from Dexcom’s G7 CGM.
The MOBILE study, published in the Journal of the American Medical Association, found that people with type 2 diabetes who use basal, or background, insulin, benefited from the use of CGM. With the publication of the MOBILE data, Dexcom has demonstrated significant outcomes driven by its CGM technology in randomized controlled trials across the full spectrum of insulin use in people with diabetes.
Key clinical benefits of Dexcom CGM use in this population included:
- Increased time in range
- Significant A1c reduction
- More patients reaching A1c goals
- A profound decrease in hyperglycemia
The randomized clinical trial was led by HealthPartners Institute’s International Diabetes Center and coordinated by The Jaeb Center for Health Research in Tampa, Fla.
“The clinical benefits of Dexcom CGM were seen across all patient demographics regardless of age, education, numeracy or socioeconomic status,” says Society member David Price, MD, vice president of medical affairs at Dexcom. “The MOBILE study design also affirms our ability to meet the needs of the diverse communities we serve.”
MOBILE Study Findings
- The group of patients using Dexcom CGM spent an average of 3.8 hours more each day within the optimal range of blood glucose levels (70-180 mg/dL), 3.6 hours less each day in the very high glucose range (>250 mg/dL), and with a reduction in CGM measured hypoglycemia in the CGM group compared to the finger-stick glucose monitoring group
- 63% of patients using CGM to guide therapy adjustments had an HbA1c less than 8% compared to only 39% of patients using finger-stick glucose reading
- The group using CGM to guide therapy and lifestyle adjustments also had significantly lower HbA1c levels (9.1 to 8.0%) than the group of patients using traditional finger-stick glucose monitoring (9.0 to 8.4%); this was an adjusted difference in mean change in HbA1c of −0.4%, 95% CI –0.8% to −0.1%, P=0.02
- Adherence and satisfaction were also high among the CGM group
That was just the first half of 2021, and as always, this piece could go on and on. Advancements in endocrinology continue to be made, even as this issue appears online. Can’t wait to see what’s next.