On January 17, 2013 Cancer Research UK and its commercial arm Cancer Research Technology (CRT) reported a trial of an experimental drug shown to simultaneously block many enzymes that control cancer cell growth and death (Press release, Cancer Research Technology, 17 17, 2013, View Source [SID1234523263]). The ‘master-switch’ experimental drug, owned by Astex Pharmaceuticals, could potentially treat a range of cancer types.

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Cancer Research UK’s Drug Development Office (DDO) will fund, manage and sponsor this early-stage Phase I clinical trial of up to 40 patients at The Institute of Cancer Research, London, and The Royal Marsden Hospital.

The drug, AT13148, is one of eight drugs to be developed through Cancer Research UK’s Clinical Development Partnerships (CDP) programme, which is a joint initiative between the charity’s DDO and CRT. The programme develops promising cancer drugs that pharmaceutical companies do not have the resources to progress through early phase clinical trials to see if they can benefit cancer patients. Without this programme many promising drugs would be left on the shelves gathering dust.

AT13148 is a type of drug called a kinase inhibitor. Research in the laboratory has shown it can simultaneously block several different enzymes that control cell growth and cell death, and the drug killed a range of cancer cell types including sarcoma, breast and prostate. Many drugs block only a single enzyme and scientists hope that switching off cell signals at multiple points at the same time could increase the effectiveness of this drug.

Dr Udai Banerji, Cancer Research UK senior clinical lecturer at The Institute of Cancer Research and honorary consultant in medical oncology at The Royal Marsden, said: "There’s an urgent need to discover and develop new ways to beat cancers that do not respond to the treatments we have at the moment. By targeting cancer cells at a range of weak spots instead of just one, tumours will be less likely to develop resistance to this treatment. We’re very pleased that this multi-target drug has now reached patients in the clinical trial stage.

"It’s thanks to the generosity and time of patients that it’s possible to carry out clinical trials like this that could lead to new treatments for patients in the future."

The novel agent came into the DDO requiring extensive preclinical development work.

Cancer Research UK scientists at the DDO and those funded at The Institute of Cancer Research demonstrated that the drug would be suitable for patients and, working together with specialist manufacturing organisations, developed a sophisticated method to make the drug in its most basic form. Finally, Cancer Research UK’s Formulation Unit at the University of Strathclyde manufactured the drug for the trial.

The molecule was originally discovered by scientists on the PKB drug discovery programme, a collaboration between Astex Pharmaceuticals, CRT and The Institute of Cancer Research, which ran from 2003 through to 2006.

Harren Jhoti, Astex Pharmaceuticals president and director, said: "We are very gratified with the progress that the collaboration has achieved and that this work has progressed into the clinic."

Astex Pharmaceuticals can decide to develop the drug further based on the Phase I/IIa clinical trial data. If it chooses not to, Cancer Research Technology has the rights to secure an alternative partner and ensure the drug has every possible chance of reaching patients. The charity will receive a share of revenues generated by the drug to be channelled back into life-saving research.

Dr Victoria John, head of clinical partnerships at Cancer Research UK’s Drug Development Office, said: "We’re delighted to open the first clinical trial of this experimental drug to find out if it can benefit cancer patients in the future.

"This molecule was brought to us at a very early stage in its development and, with the preclinical work now completed, we’re extremely pleased it’s obtained regulatory approval to enter the clinic.

"We’ve developed this molecule through our Clinical Development Partnerships initiative that has allowed us to form strong links with industry to take this promising drug forward. Without the programme it may have remained undeveloped and the clinical trial simply would not have been possible."

On January 16, 2013 MonoSol Rx, the developer of PharmFilm drug delivery technology, reported that it has licensed Zuplenz (ondansetron) to Vestiq Pharmaceuticals, a specialty pharmaceutical company focused on innovative therapeutic remedies within the supportive care markets (Press release, MonoSol Rx, JAN 16, 2013, View Source [SID:1234508916]). Zuplenz is an oral soluble film (OSF) for the prevention of chemotherapy-induced, radiotherapy-induced, and postoperative nausea and vomiting. The licensing agreement comprised an undisclosed upfront payment from Vestiq, as well as double digit royalty payments from sales of Zuplenz. Vestiq relaunched Zuplenz in the United States in the fourth quarter of 2012. The approval of Zuplenz by the U.S. Food and Drug Administration (FDA) makes it the first oral soluble lingual film product approved by the FDA as a prescription medication, based on MonoSol Rx’s proprietary PharmFilm technology.

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A. Mark Schobel, President and CEO of MonoSol Rx, stated, "We are excited that Zuplenz is once again available to meet the needs of patients. We have found the right partner in Vestiq Pharmaceuticals and are excited about their ability to positively impact the supportive care market. We know that this oral film delivery of the drug ondansetron fulfills a significant unmet need, as we have fielded a continuous stream of inquiries from doctors and nurses regarding the availability of Zuplenz. Providers are now able to ensure their patients receive the best care possible by utilizing our innovative drug delivery technology to eliminate swallowing issues and discomfort associated with chemotherapy, radiotherapy, and surgery. Today’s announcement reinforces MonoSol Rx’s position as a leader in the film space, and our continued dedication to patients in need."

"We are pleased to be working with MonoSol Rx to relaunch Zuplenz into the U.S. market," said Martin Baum, Chairman and CEO of Vestiq Pharmaceuticals. "The oral film delivery technology is a major breakthrough for ease of use and compliance for supportive care patients, who consistently have difficulty swallowing. We intend to build on the initial acceptance of Zuplenz by the oncologists, general surgeon and oncology nurse communities, who are now able to provide their patients with an alternative product for nausea and vomiting."

Zuplenz is a unique formulation of ondansetron developed using MonoSol Rx’s proprietary PharmFilm technology, and co-developed with partner APR Applied Pharma Research s.a. of Switzerland. It is based on a novel and proprietary oral drug delivery technology platform and consists of a polymeric OSF containing ondansetron. Once placed in the mouth, it dissolves in a few seconds and is swallowed with saliva without the need for water.

(Press release, Onconova, JAN 9, 2013, View Source [SID:1234506143])

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On January 8, 2013 Cytochroma reported that it has entered into a definitive agreement with OPKO Health, Inc. (NYSE:OPK) under which Cytochroma, a privately held pharmaceutical company with operations in Markham, ON and Bannockburn, IL, will be acquired by OPKO (Press release, Opko Health, JAN 8, 2013, View Source [SID:1234512927]). Through this transaction, OPKO will acquire worldwide rights to Cytochroma’s two lead product candidates: Replidea (coded CTAP101 Capsules), a vitamin D prohormone to treat secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency; and, AlpharenTM (Fermagate Tablets), a non-absorbed phosphate binder to treat hyperphosphatemia in dialysis patients. Both products are in phase 3 development in the United States. Cytochroma’s officers will join the OPKO management team, and all other Cytochroma employees will be retained by OPKO.

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Replidea has been shown in a phase 2b clinical trial to effectively and safely treat SHPT and the underlying vitamin D insufficiency in pre-dialysis patients. Vitamin D insufficiency arises in CKD due to the abnormal upregulation of CYP24, an enzyme which destroys vitamin D and its metabolites. Studies in CKD patients have demonstrated that currently available over-the-counter and prescription vitamin D products cannot reliably raise blood vitamin D prohormone levels or effectively treat SHPT.

"OPKO intends to market Replidea along with OPKO’s proprietary point-of-care vitamin D diagnostic test currently in development," stated Phillip Frost, MD, OPKO’s CEO and Chairman. "We envision these remarkable products as part of the foundation for a new and markedly improved standard of care for chronic kidney disease patients."

"We are pleased that OPKO and Cytochroma have joined forces to improve the care of kidney patients," commented Alan J. Lewis, PhD, Cytochroma’s Chairman. "The combined companies are well positioned to become a major new global player in the chronic kidney disease space."

Alpharen has been shown safe and effective in treating hyperphosphatemia (elevated serum phosphorus) in the phase 2 and 3 clinical trials undertaken to date in dialysis patients. Hyperphosphatemia exacerbates SHPT and promotes bone disease, soft tissue mineralization and progression of kidney disease. Approximately 90% of dialysis patients in the United States require regular treatment. Cytochroma acquired global rights to AlpharenTM from INEOS Healthcare in 2010.

About Chronic Kidney Disease
CKD is a condition characterized by a progressive decline in kidney function. The kidney is normally responsible for excreting waste and excess water from the body, and for regulating various hormones. CKD is classified in five different stages – mild (stage 1) to severe (stage 5) disease – as measured by the kidney’s glomerular filtration rate. According to the National Kidney Foundation, CKD afflicts over 26 million people in the US, including more than eight million patients with moderate (stages 3 and 4) and severe (stage 5) forms of CKD. In stage 5 CKD, kidney function is minimal to absent and patients require regular dialysis or a kidney transplant for survival.

About Vitamin D Insufficiency
Vitamin D insufficiency is a condition in which the body has low vitamin D stores, characterized by inadequate blood levels of vitamin D prohormones, collectively known as 25-hydroxyvitamin D. An estimated 70-90% of CKD patients have vitamin D insufficiency, which can lead to SHPT and resultant debilitating bone diseases.

About Secondary Hyperparathyroidism (SHPT)
SHPT is a condition commonly associated with CKD in which the parathyroid glands secrete excessive amounts of parathyroid hormone (PTH). SHPT arises as a result of vitamin D insufficiency or impaired kidney function that prevents sufficient production of vitamin D hormones to properly regulate calcium and phosphorus metabolism, and PTH secretion. Prolonged elevation of blood PTH causes excessive calcium and phosphorus to be released from bone, leading to elevated serum calcium and phosphorus, softening of the bones (osteomalacia) and calcification of vascular and renal tissues. SHPT affects 40-60% of patients with moderate CKD and approximately 90% of patients with severe CKD.

About Hyperphosphatemia
Hyperphosphatemia, or elevated serum phosphorus, is common in dialysis patients and tightly linked to the progression of SHPT. The kidneys provide the primary route of excretion for excess phosphorus absorbed from ingested food. As kidney function worsens, serum phosphorus levels increase and directly stimulate PTH secretion. Stage 5 CKD patients must reduce their dietary phosphate intake and usually require regular treatment with phosphate binding agents to lower serum phosphorus to meet the recommendations of the National Kidney Foundation’s Clinical Practice Guidelines that serum phosphorus levels should be maintained at <5.5 mg/dL.

On January 8, 2013 OPKO Health, Inc. (NYSE:OPK) reported that it has entered into a definitive agreement to acquire Cytochroma Inc. (Markham, Canada) whose lead products, both in phase 3 clinical trials, are Replidea (coded CTAP101 Capsules), a vitamin D prohormone to treat secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency, and Alpharen, a non-absorbed phosphate binder to treat hyperphosphatemia in dialysis patients (Press release, Opko Health, JAN 8, 2013, View Source [SID:1234512697]).

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Replidea has been shown in a phase 2b clinical trial to effectively and safely treat SHPT and the underlying vitamin D insufficiency in pre-dialysis patients. Vitamin D insufficiency arises in CKD due to the abnormal upregulation of CYP24, an enzyme which destroys vitamin D and its metabolites. Studies in CKD patients have demonstrated that currently available over-the-counter and prescription vitamin D products cannot reliably raise blood vitamin D prohormone levels or effectively treat SHPT.

"OPKO intends to market Replidea along with our proprietary point-of-care vitamin D diagnostic test currently in development," stated Phillip Frost, MD, CEO and Chairman. "We envision these remarkable products as part of the foundation for a new and markedly improved standard of care for chronic kidney disease patients having SHPT and/or hyperphosphatemia."

Alpharen has been shown safe and effective in treating hyperphosphatemia in the phase 2 and 3 clinical trials undertaken to date in dialysis patients. Hyperphosphatemia (elevated serum phosphorus) exacerbates SHPT and promotes bone disease, soft tissue mineralization and progression of kidney disease. Approximately 90% of dialysis patients in the United States require regular treatment.

Cytochroma’s officers, including Charles W. Bishop, PhD, CEO, an authority on developing and commercializing successful new vitamin D therapies, and Eric J. Messner, MBA, having a noteworthy track record in pharmaceutical business development and in marketing and sales in the CKD arena, will join the OPKO management team. Prior to Cytochroma, Dr. Bishop and Mr. Messner held key positions at Bone Care International, Inc., a leader in vitamin D therapeutics acquired by Genzyme Corporation, now a division of Sanofi.

About Chronic Kidney Disease

CKD is a condition characterized by a progressive decline in kidney function. The kidney is normally responsible for excreting waste and excess water from the body, and for regulating various hormones. CKD is classified in five different stages — mild (stage 1) to severe (stage 5) disease — as measured by the kidney’s glomerular filtration rate. According to the National Kidney Foundation, CKD afflicts over 26 million people in the US, including more than eight million patients with stage 3 and 4 CKD. In stage 5, kidney function is minimal to absent and patients require regular dialysis or a kidney transplant for survival.

About Vitamin D Insufficiency

Vitamin D insufficiency is a condition in which blood levels of vitamin D prohormones, collectively known as 25-hydroxyvitamin D, are inadequate. An estimated 70-90% of CKD patients have vitamin D insufficiency which can lead to SHPT and its debilitating consequences.

About Secondary Hyperparathyroidism (SHPT)

SHPT is a condition commonly associated with CKD in which the parathyroid glands secrete excessive amounts of parathyroid hormone (PTH). SHPT arises as a result of vitamin D insufficiency or impaired kidney function. Prolonged elevation of blood PTH causes excessive calcium and phosphorus to be released from bone, leading to elevated serum calcium and phosphorus levels, softening of the bones (osteomalacia) and calcification of vascular and renal tissues. SHPT affects 40-60% of patients with stage 3 and 4 CKD and approximately 90% of patients with stage 5.

About Hyperphosphatemia

Hyperphosphatemia, or elevated serum phosphorus, is common in dialysis patients and tightly linked to the progression of SHPT. The kidneys provide the primary route of excretion for excess phosphorus absorbed from ingested food. As kidney function worsens, serum phosphorus levels increase and directly stimulate PTH secretion. Stage 5 CKD patients must reduce their dietary phosphate intake and usually require regular treatment with phosphate binding agents to lower serum phosphorus to meet the recommendations of the National Kidney Foundation’s Clinical Practice Guidelines that serum phosphorus levels should be maintained at < 5.5 mg/dL.