Sparrow Pharmaceuticals Hopes To Change The Future Of Endocrinology

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical

Go ahead and continuously improvement iStock-1295289697

Sparrow Pharmaceuticals is an emerging biopharma company on a mission to help patients suffering from an excess of corticosteroids, with a focus on Cushing’s syndrome, autonomous cortisol secretion (ACS), and polymyalgia rheumatica (PMR).

Cushing’s and ACS are both caused by an excess of cortisol produced by tumors. Patients with Cushing’s can present physically with a fatty hump between their shoulders, a rounded face, and pink or purple stretch marks on their skin. Cushing’s syndrome and ACS can both result in high blood pressure, bone loss, type 2 diabetes, weight gain, and mood, cognition, and sleep disorders. Any of those symptoms may be side effects for patients with conditions such as PMR who rely on long-term treatment with corticosteroid medications such as prednisone.

“Cushing’s syndrome impacts around 20,000 patients in the U.S. alone,” says David Katz, Chief Scientific Officer for Sparrow. “Approximately 50% of those patients can be cured by surgery, but some will develop another tumor years later. ACS is an under-recognized condition, but it may affect up to 3 million patients in the U.S. There are also around 2 million people in the U.S. who rely on long-term use of corticosteroid medications to control autoimmune diseases and other conditions.”

The treatments being developed by Sparrow are based on recognition that cortisol and corticosteroid medications are activated in certain tissues such as the liver, bone, fat, and brain, where in excess they act to cause toxicity. The company’s investigational drugs inhibit HSD-1, the enzyme responsible for that activation.

Sparrow is about to launch a Phase 2 trial for Cushing’s syndrome. In early 2022 the company will also begin two additional Phase 2 trials for ACS and PMR, a common autoimmune disease in elderly patients. PMR is an arthritic syndrome characterized by a phenomenon known as claudication, which means the more you use a limb, the more it hurts and the harder it is to use. “For example, the more a PMR patient walks, the more painful and stiff their legs will become,” says Katz. “If they’re trying to do anything with their arms, the arms will get stiffer and more painful. The disease is pretty debilitating in terms of physical function. The only approved treatment for PMR is steroids, which have side effects such as diabetes, hypertension, osteoporosis, and fractures.”

Unknown Clinical Challenges

Katz is excited about the clinical trials for ACS and PMR because no sizable interventional trials have been reported in either of those conditions.

“We’re going into a completely new area, and we don’t know what we’re going to encounter in terms of patient recruitment and retention,” says Katz. “There is also no strong precedent for how to get approval for a drug in these conditions. The only treatment indicated for PMR is steroids, and that came without any efficacy clinical trials. There are no drugs approved for ACS. It’s hard to anticipate the challenges we will face when we are in an area that is very new.”

Patient centricity is a topic that is very important to Katz, and he spends a lot of time thinking about how to make trials a more pleasant experience for patients by limiting the burden placed on them. He notes that can sometimes be a difficult trade-off because of the procedures that must be performed to meet regulatory standards.

“In Cushing’s syndrome clinical care and clinical trials, the standard way for someone’s cortisol level to be measured is a 24-hour urine collection,” states Katz. “That involves looking at the amount of cortisol in the urine over a 24-hour period. That collection is inconvenient and burdensome, and the patient must then carry it somewhere to be analyzed.”

Sparrow hopes to shift that collection to a spot urine sample, like what patients would experience during a physical. The patient would urinate into a cup and hand it off to a clinic employee for analysis. The process would be much simpler and less burdensome for the patient. Sparrow will first need to prove that in a clinical trial the spot sample will work as well or better than the 24-hour collection. Subjects in the initial clinical trials will have to contribute the 24-hour collections so that Sparrow can demonstrate that future patients will not need to do so.

The Future of Endocrinology

Katz has a positive outlook on the future of endocrinology. Sparrow’s leading drug candidate, SPI-62, is an oral, small-molecule HSD-1 inhibitor. In four clinical trials, it demonstrated potent targeting of HSD-1 in both the brain and liver, and significantly lowered cortisol levels in the liver. The studies also showed a favorable safety and tolerability profile.

“If we are successful at developing SPI-62, I believe it will change the field of endocrinology,” says Katz. “We aim to shift the focus in Cushing’s syndrome to intracellular cortisol as the main driver of symptoms. What I mean by that is if we find that SPI-62 substantially reduces symptoms and that the degree of inhibition of our target HSD-1 correlates well with clinical improvement, then we can get to a new standard of care. We can potentially get rid of the 24-hour urine collections, which will be a big relief to patients. Additionally, many of today’s drugs have a side effect called adrenal insufficiency, which results when the drugs either reduce cortisol too much or completely block activity. Many of today’s drugs also require frequent monitoring and dose titration to prevent adrenal insufficiency. We believe that with HSD-1 inhibition we might avoid adrenal insufficiency as well.”

Katz is hopeful patients treated with SPI-62 will not require monitoring and dose titration. That proof will take years and lots of clinical trials. Sparrow may also produce the first targeted therapy for ACS. That could improve the recognition of ACS as a prevalent form of hypercortisolism and a substantial cause of morbidity and mortality.

“ACS is probably the most under-recognized condition in endocrinology based on recent epidemiological studies,” adds Katz. “It’s possible that as few as 3% of patients who have ACS actually have a diagnosis.  That is shocking for a condition that is associated with a lot of cardiometabolic and bone morbidity, negative effects on mood and cognition, sleep, and muscle strength, and is associated with excess mortality. We want to bring attention to this condition by bringing out a targeted therapy to treat a spectrum of symptoms by getting to the root cause of them.”

From https://www.clinicalleader.com/doc/sparrow-pharmaceuticals-hopes-to-change-the-future-of-endocrinology-0001

A Team Effort to Treat a Pea-Sized Gland

HYANNIS – Endoscopic surgery for pituitary tumors involves the use of small instruments, but neurosurgeon Nicholas Coppa, MD, FAANS, is quick to say it takes a big team to make the surgeries a success.

“It’s very much a collaborative effort among endocrinology, neurosurgery and otolaryngology specialties,” he said.

Dr. Coppa frequently works with endocrinologist Catalina Norman, MD, PhD, and ear, nose and throat surgeon Ross Johnston, MD.

The pituitary gland sits at the base of the brain. It makes important hormones that control several different systems in the body and help maintain normal body function.

“The overwhelming majority of patients with big tumors present with visual problems,” said Dr. Coppa. “They get tunnel vision from a tumor putting pressure on the vision nerves.

Many patients’ pituitary problems are detected incidentally while the physician is trying to diagnose a set of symptoms, most commonly headaches, he added. A variety of asymptomatic tumors are detected this way.

A subset of pituitary tumors secrete excess hormones, which create syndromes characterized by whatever hormone is being secreted in excess, Dr. Coppa added. Oftentimes these problems are diagnosed by an endocrinologist.

Before coming to Neurosurgeons of Cape Cod – now known as Cape Cod Healthcare Neurosurgery – in 2013, Dr. Coppa was professor of skull base surgery at Oregon Health and Science University’s Northwest Pituitary Center. He has performed more than 200 endoscopic surgeries for pituitary tumors, sinonasal malignancies and anterior skull base encephaloceles. The procedure is fairly new on Cape Cod, he said.

The pituitary gland is about the size of a pea, so operating on it is a tricky and delicate procedure.

The surgeon commonly works with an endoscope inserted through one nostril, and microsurgical instruments through the other nostril. This allows him to maneuver to the surgical area.

According to the Northwest Pituitary Center’s web site, “The tube is connected to a TV monitor that helps your doctor see the surgical area even more clearly than with a microscope. Your doctor can also use intraoperative neuro-navigation to perform image-guided surgery, based on a pre-operative CT scan or MRI. This helps the doctor see exactly where the tumor is and avoid damaging healthy brain tissue that is nearby.”

Nasal endoscopy for the neurosurgeon has really taken off in the last 10 years, according to Dr. Coppa. The main reason for the increase is because the technique allows better visualization of the anatomy, he said.

“We find that it allows, at least in my experience, more maneuverability of your micro-surgical instruments. That’s been very satisfying for patients. The nasal morbidity [adverse effects] is lower compared to historic ways of doing it.”

Ear, nose and throat doctors use trans-nasal surgery to treat many sinus conditions, said Dr. Coppa. But the procedure is predominantly used by neurosurgeons for pituitary tumors, other tumors of the skull base and malignancies of the sinus cavity that often invade the brain.

After endoscopic pituitary surgery, patients are typically in the hospital for several days and resume day-to-day activities within that first week.

By BILL O’NEILL, OneCape Health News

 

From http://www.capecod.com/newscenter/a-team-effort-to-treat-a-pea-sized-gland/

Researchers at Department of Endocrinology and Diabetes Release New Data on Cushing Syndrome

By a News Reporter-Staff News Editor at Biotech Week — Research findings on Adrenal Gland Diseases are discussed in a new report. According to news reporting originating from Melbourne, Australia, by NewsRx correspondents, research stated, “Stereotactic radiation therapy has emerged as an alternative to conventional radiotherapy for treatment of Cushing disease. The aim of this study was to investigate the efficacy and safety of this treatment.”

Our news editors obtained a quote from the research from the Department of Endocrinology and Diabetes, “Records of patients with Cushing disease treated with stereotactic radiation were reviewed. Seventeen patients underwent stereotactic radiosurgery.”

According to the news editors, the research concluded: “Ten achieved remission after a mean of 23 (95% confidence interval, 15-31) months, and two developed hormone deficiencies.”

For more information on this research see: Stereotactic radiosurgery for treatment of Cushing disease: an Australian experience. Internal Medicine Journal, 2012;42(10):1153-6. (Wiley-Blackwell – www.wiley.com/; Internal Medicine Journal – onlinelibrary.wiley.com/journal/10.1111/(ISSN)1445-5994)

The news editors report that additional information may be obtained by contacting L. Wein, Dept. of Endocrinology and Diabetes, Alfred Hospital, Melbourne, Victoria, Australia. Additional authors for this research include M. Dally and L.A Bach (see also Adrenal Gland Diseases).

Keywords for this news article include: Melbourne, Treatment, Radiotherapy, Radiation Therapy, Cushing’s Syndrome, Adrenal Gland Diseases, Australia and New Zealand.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2013, NewsRx LLC

From http://www.hispanicbusiness.com/2013/9/18/researchers_at_department_of_endocrinology_and.htm

Cyclic Cushing’s syndrome: a clinical challenge

  1. J R Meinardi1,2,
  2. B H R Wolffenbuttel2 and
  3. R P F Dullaart2

+Author Affiliations


  1. 1Department of Internal Medicine, Canisius Wilhelmina Ziekenhuis, PO Box 9015, 6500 GS Nijmegen, The Netherlands and 2Department of Endocrinology, University Medical Centre Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands
  1. (Correspondence should be addressed to: R P F Dullaart; Email:r.p.f.dullaart@int.umcg.nl)

Abstract

Cyclic Cushing’s syndrome (CS) is a rare disorder, characterized by repeated episodes of cortisol excess interspersed by periods of normal cortisol secretion. The so-called cycles of hypercortisolism can occur regularly or irregularly with intercyclic phases ranging from days to years.

To formally diagnose cyclic CS, three peaks and two troughs of cortisol production should be demonstrated. Our review of 65 reported cases demonstrates that cyclic CS originates in 54% of cases from a pituitary corticotroph adenoma, in 26% from an ectopic ACTH-producing tumour and in about 11% from an adrenal tumour, the remainder being unclassified. The pathophysiology of cyclic CS is largely unknown.

The majority of patients with cyclic CS have clinical signs of CS, which can be either fluctuating or permanent. In a minority of patients, clinical signs of CS are absent. The fluctuating clinical picture and discrepant biochemical findings make cyclic CS extremely hard to diagnose. Clinicians should therefore be aware of this clinical entity and actively search for it in all patients with suspected CS but normal biochemistry or vice versa.

Frequent measurements of urinary cortisol or salivary cortisol levels are a reliable and convenient screening tool for suspected cyclic CS. Cortisol stimulation or suppression tests may give spurious results owing to spontaneous falls or rises in serum cortisol at the time of testing. When cyclic CS is biochemically confirmed, further imaging and laboratory studies are guided by the presence or absence of ACTH dependency. In cases of suspected ectopic ACTH production, specific biochemical testing for carcinoids or neuroendocrine tumours is required, including measurements of serotonin in platelets and/or urine, chromogranin A and calcitonin.

Read the entire article here:  http://www.scribd.com/doc/159503297/Cyclic-Cushing%E2%80%99s-syndrome-a-clinical-challenge

Laparoscopic Bilateral Transperitoneal Adrenalectomy For Cushing Syndrome

Surgical Laparoscopy, Endoscopy & Percutaneous Techniques, 07/16/2013  Clinical Article

Aggarwal S et al. –

Laparoscopic adrenalectomy is well established for treatment of adrenal lesions. However, bilateral adrenalectomy for Cushing syndrome is a challenging and time–consuming operation.

The authors report their experience of laparoscopic bilateral adrenalectomy for this disease in 19 patients. Laparoscopic bilateral adrenalectomy for Cushing syndrome is feasible and safe. It confers all the advantages of minimally invasive approach such as less postoperative pain, shorter hospitalization, lesser wound complications, and faster recovery.

The advantages of the laparoscopic approach have led to an earlier referral for bilateral adrenalectomy by endocrinologist in patients with failed pituitary surgery.

 

This article is available on PubMed

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