Growth Hormone: Improving Patients’ Lives and Boosting Mature Product Portfolios

Jul 07, 2017
Volume 37, Issue 7

easypod—an automated drug delivery device manufactured by Merck KGaA, Darmstadt, Germany for its recombinant human growth hormone, Saizen—is the only electronic, fully automated injection device for growth hormone therapy. Its features include automated dose delivery and prescription tracking, which records injection history and any missed injections, and allows patients to know when to change their cartridge by displaying how much medicine is left in the device.

Speaking to Pharm Exec, Merck KGaA’s Chief Operating Officer of Biopharma, Simon Sturge, outlines the device’s development and highlights its position in the context of a changing treatment-adherence landscape that could bring benefits both to patients and mature product portfolios.

PE: Are digital interventions in patient adherence becoming more of a focus at your company?

STURGE: Absolutely. We are a major player in the area of diabetes, for example, and as we all know, lifestyle has a huge impact on the outcome of diabetes. How much we as a company should be able to offer a whole package that helps to support the lifestyle changes needed is a very important element of us preventing or delaying the onset of diabetes. In other areas, many people who are sick have a degree of depression. There are excellent apps that are reimbursed in some countries to help treat depression, and those sorts of things should be offered as part of a solution. We believe it is an essential part of our business to look holistically at the patient and bring to that patient as many practical things as possible to help them overcome their disease.

However, innovative drugs are also at the core of what we do. A few years ago, we established a clear strategy of driving innovation in the area of specialty products. This has taken quite some time from an R&D perspective, but it is now coming to fruition, with a focus on the areas of oncology, immuno-oncology, and immunology. We have a number of exciting innovative products coming to market, and what we’re also seeing is substantial growth on the portfolio of our established products, one of which is our growth hormone, Saizen.

PE: How much did you incorporate patients’ adherence behaviors in developing easypod?

STURGE: Quite a few of our products are biotech products that need to be given via injection. Understanding the patient need around that product, how they inject, what the issues are, particularly for children, has helped drive our e-health and digital platform. We have a number of different applications around our growth hormone product, but the most sophisticated is easypod. The device sends administration data such as time and dose to the cloud via a mobile device or home network, and then shares that data with the treating physician or carer, to be able to understand the usage of that product.

There are digital ways that you can track people and their activities, of course, but what we’ve found is that you can’t beat having somebody almost living with a patient. In some circumstances we do that. We use an external group, and they send an observer to stay with a family for several days to really understand the practical issues that surround the use of the product. It’s those kinds of insights that really help to provide solutions that are practical and that address genuine issues that the patient wants to overcome.

Adherence in using an injectable product in a chronic environment can be very low, as low as 25%, but we’ve seen in controlled studies that with easypod that we can take that up to close to 90%.

[Ramy Sourial, growth hormone franchise director at Merck KGaA, Darmstadt, Germany, adds: We worked with patient organizations and healthcare providers at different stages of planning the device, and we used focus groups and market researchers to identify the needs. During development, we conduct regular tests to check that we are on the right track. And when the product is on the market, we continue to improve the device, even small things like designing covers and designing smaller needles.]

PE: Can this higher adherence be sustained in a real-world setting?

STURGE: We’re moving to very elegant devices, more universal devices; physicians and caregivers are becoming a lot more comfortable using the data that is generated. Where the big transition needs to take place is still with the payers. The NHS (National Health Service) is one of the most sophisticated providers in terms of understanding usage of products on a more holistic basis and has a willingness to work with the pharma industry on pricing and payment mechanisms that ultimately link efficacy with payment. As governments, payers, and the industry work more closely together, this will be of benefit to all parties and especially patients.

Our responsibility as a pharma company is broader than just supplying the drug. We have worked with the NHS on schemes where they only pay if the drug is used. If adherence levels are low, they don’t pay. In some of the pilot schemes with the NHS in a real-world setting, we were getting those adherence rates of close to 90%; we think that is quite achievable in everyday use. But there’s always things you can add, adding digital gains into these things to encourage children to use these devices on a daily basis; it’s a dynamic process and our aim is to try and maintain these increased adherence rates.

PE: What would you say are the remaining challenges in patient adherence?

STURGE: One of the biggest challenges we face is data privacy, the different data privacy laws country by country. If you end up having to develop software that has to be different in every country, it becomes less meaningful. Respecting and understanding data privacy but having a broader global alignment on data privacy laws in our industry will help everybody.

It will remain a sticking point for quite some time; it’s a highly complex and politically emotive subject, for very good reasons. But our concern isn’t around data privacy, per se—it’s consistency of the regulations thereof.

 

Julian Upton is Pharm Exec’s European and Online Editor. He can be reached at julian.upton@ubm.com

From http://www.pharmexec.com/improving-patients-lives-and-boosting-mature-product-portfolios

For Pituitary Tumors, Gamma Knife™ Radiosurgery Offers Better Tumor Control

For many patients with pituitary tumors, initial surgical intervention is followed quickly by Gamma Knife™ radiosurgery. The benefits of using this radiosurgical intervention are many, and can offer better tumor control and a more positive long-term prognosis compared to surgery alone.

San Diego, CA (PRWEB) July 03, 2017

Worldwide, up to 20% of all brain tumors—those confined within the skull—are identified as pituitary adenomas.(1) Each year, almost 10,000 new pituitary tumors are diagnosed in the United States alone, with the vast majority of these tumors being pituitary adenomas. As efforts to improve treatment for patients with pituitary tumors continue, researchers are discovering just how powerful treatment with Gamma Knife™ radiosurgery can be, at facilities like the San Diego Gamma Knife Center® (SDGKC).

Recent studies have shown compelling results for patients who received treatment with Gamma Knife™ radiosurgery following traditional surgery for pituitary tumor removal. Overall, tumor control was achieved with Gamma Knife™ treatment in up to 94% of patients studied.(1) For up to 85% of these patients, tumor control was still achieved 10 years after treatment with the Gamma Knife™.(6)

Pituitary adenomas are typically benign, but they can still cause significant problems for patients due to their location in the brain.(3) Many of these tumors also secrete certain hormones, which can ultimately change the way patients’ bodies function.(3) In most cases, the first line of defense in dealing with pituitary tumors involves surgical removal of as much of the tumor as possible; however, residual tumor tissue can exist in the brain after this process.(4)

Even though many physicians choose surgery as an initial treatment, Gamma Knife™ radiosurgery can be either a primary or secondary choice for the management of pituitary tumors. Most often, Gamma Knife is used as a secondary treatment following surgery.(5) A growing number of studies show that treating patients with the Gamma Knife™ after surgical removal of pituitary tumors is extremely beneficial for patients and can dramatically improve their long-term tumor control results.

Dr. Kenneth Ott, neurosurgeon of SDGKC®, said, “The extreme accuracy of Gamma Knife radiosurgery allows effective treatment of residual pituitary tumors following surgery to remove much of the tumor volume. In my practice, residual tumors which I have operated on are treated with Gamma Knife radiosurgery which almost always stops further growth.”

Dr. Ott continued to explain that Gamma Knife radiosurgery is more effective than prior external beam methods of radiation and avoids complications to near-by sensitive structures. Tumors within a few millimeters of the optic nerves can be safely treated because of the frame-based fixation and software advantages of Gamma Knife. Tumors which are slowly growing can also be effectively treated without the need for surgery, as long as there is no visual loss from tumor compression of the optic nerves.

Patient outcomes can also be influenced by how soon after brain surgery they receive treatment with the Gamma Knife™. In many cases, patients benefit the most from early intervention with radiosurgery; some studies have suggested that patients who receive Gamma Knife treatment more than six months after their initial surgery are at a significantly greater risk of pituitary tumor progression nearly six years post-surgery.(7)

“Pituitary tumors, in general should be treated before the tumor compresses the overlying optic nerves,” said Dr. Ott. “The earlier the treatment begins, the better. The final decision regarding Gamma Knife should be made on a case-by-case basis by a surgeon who is experienced in surgery and radiosurgery.”
About San Diego Gamma Knife Center:
Since its opening, the San Diego Gamma Knife Center® has treated over 4,000 patients with various brain disorders from around the world. The facility is equipped to provide advanced radiosurgical treatment for a variety of conditions, including metastatic brain tumors, primary brain tumors, arteriovenous malformations, and functional disorders such as trigeminal neuralgia and cluster headaches.

On the campus of Scripps Memorial Hospital, the Center offers the use of its facilities to some of the top neurosurgeons and radiation oncologists in Southern California. It’s also a proud partner of the Neurosciences Department of Scripps Memorial Hospital La Jolla, helping to provide accurate diagnoses, treatment and support for a range of neurological conditions and disorders. To learn more about the San Diego Gamma Knife Center®, please visit http://www.sdgkc.com.

Sources:
1.    Sheehan J, et al. Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: A multicenter study. Journal of Neurosurgery. 2013;119:446. http://thejns.org/doi/full/10.3171/2013.3.JNS12766. Accessed June 20, 2017.
2.    What Are the Key Statistics About Pituitary Tumors? American Cancer Society. https://www.cancer.org/cancer/pituitary-tumors/about/key-statistics.html. Accessed June 20, 2017.
3.    What Are Pituitary Tumors? American Cancer Society. https://www.cancer.org/cancer/pituitary-tumors/about/what-is-pituitary-tumor.html. Accessed June 20, 2017.
4.    Radiation—Gamma Knife Radiosurgery for Pituitary Adenomas. Pituitary Network Association. https://pituitary.org/medical-resources/pavilions/diagnostics-scanning-and-radiological-pavilion/diagnostics-scanning-and-radiological-archive/radiation-gamma-knife-radiosurgery-for-pituitary-adenomas. Accessed June 20, 2017.
5.    Gamma Knife Radiation Therapy for Pituitary Tumors—Candidates for Gamma Knife Treatment. The Pituitary Society. http://pituitarysociety.org/patient-education/pituitary-disorders/gammaradiation/candidates. Accessed June 20, 2017.
6.    Lee C, et al. Initial Gamma Knife radiosurgery for nonfunctioning pituitary adenomas. Journal of Neurosurgery. 2014;120:647. http://thejns.org/doi/full/10.3171/2013.11.JNS131757. Accessed June 20, 2017.
7.    Gamma Knife Radiosurgery Safe in Early Pituitary Tumor. Medscape. http://www.medscape.com/viewarticle/879250. Accessed June 20, 2017.

For the original version on PRWeb visit: http://www.prweb.com/releases/2017/07/prweb14478413.htm

Ectopic Cushing’s syndrome associated with thoracic tumors

Results of a retrospective review conducted in southern India demonstrate that ectopic Cushing’s syndrome occurred most commonly in association with thoracic tumors.

Researchers added that early control over hypercortisolemia was necessary to prevent metabolic complications and infections, both of which had the potential to be life-threatening.

“As compared to patients with pituitary-dependent Cushing’s syndrome, patients with [ectopic Cushing Syndrome] present with a rapid progression of symptoms,” Nihal Thomas, MD, MNAMS, DNB, FRACP, professor in the department of endocrinology, diabetes and metabolism at Christian Medical College, Vellore, India, and colleagues wrote. “It is also associated with typical features of proximal muscle weakness, severe hypokalaemic metabolic alkalosis, hyperpigmentation, edema, hypertension and glucose intolerance. Early diagnosis and localization of the ectopic source of [adrenocorticotrophic hormone] is crucial, because the treatment of choice in most of these patients is complete excision of the tumor. Localizing the source of excess ACTH continues to be a challenge in most patients.”

Thomas and colleagues reviewed the records of 21 patients treated at a tertiary care center in southern India from 2006 to 2015. The researchers documented patients’ clinical features, history and images from radiological findings and PET scans, as well as details of management, follow-up and outcomes. They also compared those with ectopic Cushing’s syndrome with 20 patients who had Cushing’s disease.

Median age was 34 years. Thomas and colleagues reported that one patient demonstrated “an occult source of ACTH.” The rest had a variety of tumors: bronchial carcinoid (n = 7), thymic carcinoid (n = 7), lung malignancies (n = 3), medullary thyroid carcinoma (n = 2) and pancreatic neuroendocrine tumor (n = 1).

At presentation, muscle weakness was the most common clinical feature (95%), followed by hyperpigmentation (90%), facial puffiness (76%), easy bruising (61%), edema (57%) and striae (52%). Slightly less than half (43%) showed extensive acne. Central obesity in ectopic Cushing’s syndrome was uncommon and occurred in 14% of patients (n = 3), according to Thomas and colleagues; however, it was more prevalent (n = 18) in those with Cushing’s disease.

Median cortisol at 8 a.m. was 55.5 mcg/dL, the researchers wrote, while median 8 a.m. ACTH was 207 pg/mL. The median 24-hour urinary free cortisol level was 2,484 mcg.

Compared with patients with Cushing’s disease, those with ectopic Cushing’s syndrome had “markedly higher” midnight cortisol and ACTH, as well as basal cortisol and ACTH.

During follow-up, more than half of patients (12 of 21) with ectopic Cushing’s syndrome developed life-threatening infections. Although nine patients received surgery for their tumors, only one patient achieved a complete cure during the study period, the researchers wrote.

“In our series, patients with [ectopic Cushing’s syndrome] have more profound hypokalemia, and hypercortisolemia with higher levels of ACTH,” Thomas and colleagues wrote. “The prognosis of patients with [ectopic Cushing’s syndrome] was dependent on tumor histology. The role of a timely adrenalectomy needs to be considered in patients with hypercortisolemia unresponsive to medical management, and in patients with metastatic or recurrent disease.” – by Andy Polhamus

Disclosure: Endocrine Today was unable to confirm any relevant financial disclosures.

From https://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7Be42c81a5-fd5b-4313-9b2b-9bcbdec7f8ce%7D/ectopic-cushings-syndrome-associated-with-thoracic-tumors

Drug trial begins for Cushing’s syndrome therapy

Participant enrollment has concluded for a phase 3 trial investigating the safety and efficacy of levoketoconazole, a cortisol synthesis inhibitor, for the treatment of endogenous Cushing’s syndrome, according to a press release from Strongbridge Biopharma, the drug’s developer.

The single-arm, open-label SONICS study will include the 90 enrolled participants and may allow a small number of other patients to enroll also, according to the release.

After titration to a therapeutic dose of levoketoconazole (Recorlev), participants will maintain treatment for 6 months, the primary efficacy endpoint. Longer-term evaluation for safety will extend to 1 year. A planned 6-month double blind, placebo-controlled, randomized withdrawal extension, dubbed LOGICS, will include approximately half of the participants from SONICS.

“The need for a safe and effective, next-generation cortisol synthesis inhibitor, such as Recorlev, in the treatment of Cushing’s syndrome is substantial. Through achieving target enrollment in the SONICS study, we are one step closer to better understanding the clinical value of Recorlev and potentially bringing a new therapeutic treatment option to this community,” said Matthew Pauls, president and chief executive officer of Strongbridge Biopharma.

The company expects to announce results of SONICS in the second quarter of 2018 and of LOGICS in the third quarter, according to the release.

For more information:

Clinicaltrials.gov/ct2/show/NCT01838551

From https://www.healio.com/endocrinology/adrenal/news/online/%7Bdddb8b5b-e4c8-412f-b4b8-82acde8f21a2%7D/drug-trial-begins-for-cushings-syndrome-therapy

Cushing’s Syndrome, Cortisol, and Cognitive Competency: A Case Report

Abstract

Glucocorticoids are associated with immunosuppression and neuropsychiatric complications. We describe the case of a carcinoid patient with Cushing’s syndrome (CS) and neurocognitive impairment due to ectopic ACTH production who developed sepsis and died because of his family’s decision to withdraw antibiotic treatment. This report is presented to illustrate the importance of advanced-care planning in patients with CS.

Key Words: Cushing’s syndrome, Carcinoid patient, Glucocorticoids, ACTH, Immunosuppression, Neurocognitive impairment, Advanced directives

Introduction

Cushing’s syndrome (CS) is a general term for a cluster of endocrine abnormalities characterized by chronic cortisol overproduction. Characteristic clinical comorbidities include metabolic complications (e.g., visceral obesity, diabetes mellitus, and dyslipidemia), cardiovascular complications (e.g., systemic arterial hypertension, atherosclerosis, and thromboembolism), bone complications (e.g., osteoporosis and osteoarthritis) infective complications, and neuropsychiatric disorders (e.g., major depression, mania, anxiety, and cognitive impairment) [1]. CS may be exogenous and iatrogenic due to corticosteroid administration or endogenous due to excessive ACTH secretion, most commonly from a pituitary adenoma, referred to, somewhat confusingly, as Cushing’s disease, or less commonly from a nonpituitary tumor (ectopic CS) and primary adrenal neoplasms [2]. Several studies link untreated CS to fatal infectious complications [3]. This report describes the case of a 60-year-old carcinoid patient with cognitive impairment due to hypercortisolism from CS who developed bacteremia; his condition deteriorated, and he died after a decision was made to withdraw care.

Case Presentation

A 60-year-old male with metastatic bronchopulmonary neuroendocrine tumor treated on a clinical trial for over 5 months was admitted to the hospital with complaints of fever, agitation, and weakness. His medical history was significant for newly diagnosed CS secondary to ACTH secretion; he had been hospitalized 2 weeks earlier for CS-induced hyperglycemic crisis. On admission, the patient presented with classic cushingoid habitus of facial plethora, moon facies, muscle atrophy, abdominal striae, and truncal obesity. His physical examination was significant for bilateral crackles and agitation consistent with corticosteroid psychosis. The arterial blood gas analysis on room air was pH 7.497, PaCO2 29 mm Hg, PaO2 71 mm Hg, and oxygen saturation 95%.

Laboratory data were significant for hyperglycemia, hypokalemia, and leukocytosis with bandemia. The chest CT scan showed no definite evidence of pulmonary thromboembolism.

As respiratory failure was imminent, he was transferred to the intensive care unit and mechanically ventilated. The highest positive end-expiratory pressure and FiO2 required to maintain oxygenation were 5 cm H2O and 50%, respectively. Cultures were taken from bronchial secretions directly after endotracheal intubation and from urine and blood. The patient was diagnosed with Staphylococcus aureus bacteremia, and based on susceptibility testing, he was started on vancomycin and Zosyn. In addition to antibiotics, the patient received lisinopril for CS-induced hypertension and insulin sliding scale to control hyperglycemia.

Since high circulating levels of glucocorticoids due to ectopic ACTH secretion predispose to infection and impair immune function and clearance of bacteria, the immediate plan was to start him on mifepristone (600 mg daily) as a glucocorticoid receptor antagonist to counteract the immunosuppressive and cognitive effects of the endogenous hypercortisolism. As soon as the patient’s condition improved (which would have been expected given the known reversibility of hypercortisolism), cytoreductive chemotherapy would have been restarted to reduce the paraneoplastic stimulus. However, the patient’s family with medical power of attorney refused consent and withdrew him from the ventilator. The patient died shortly thereafter.

Discussion

Advance directives are written to guarantee autonomy in the event that individual decision-making capacity is lost due to disease severity or treatment [4]. However, as a blanket statement that may contain overly broad (or overly specific) prewritten blocks of text, especially for cancer patients, the content of advance directives may or may not necessarily apply to and/or the patient’s wishes may or may not be correctly interpreted during acute, temporary and potentially reversible conditions that occur during cancer treatment such as infection due to ectopic CS.

Given the potential for cognitive impairment and other acute sequelae such as difficult-to-treat infections from the development of ectopic CS, this case illustrates the importance of revisiting the advance directive when a medical diagnosis associated with temporary cognitive impairment such as CS is made.

Statement of Ethics

The authors have no ethical conflicts to disclose.

Disclosure Statement

The authors have no conflicts of interest to declare.

References

1. Pivonello R, Simeoli C, De Martino MC, Cozzolino A, De Leo M, Iacuaniello D, Pivonello C, et al. Neuropsychiatric disorders in Cushing’s syndrome. Front Neurosci. 2015;9:129. [PMC free article][PubMed]
2. Tsigos C, Chrousos GP. Differential diagnosis and management of Cushing’s syndrome. Annu Rev Med. 1996;47:443–461. [PubMed]
3. Bakker RC, Gallas PR, Romijn JA, Wiersinga WM. Cushing’s syndrome complicated by multiple opportunistic infections. J Endocrinol Invest. 1998;21:329–333. [PubMed]
4. Halpern NA, Pastores SM, Chou JF, Chawla S, Thaler HT. Advance directives in an oncologic intensive care unit: a contemporary analysis of their frequency, type, and impact. J Palliat Med. 2011;14:483–489.[PMC free article] [PubMed]

Articles from Case Reports in Oncology are provided here courtesy of Karger Publishers
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