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In the news: Cytokinetics, has initiated phase I clinical trial to investigate the pharmacokinetic profile of CK-2017357. Cytokinetics has also initiated the second part, or "Part B", of a previously initiated, Phase I clinical trial of CK-2017357 in healthy male volunteers. 

CK-2017357 is a small molecule drug that offers hope to patients suffering from detrimental and life-threatening muscle wasting and neuromuscular dysfunction. These diseases include amyotrophic lateral sclerosis (ALS), myasthenia gravis, sarcopenia, claudication, cachexia, and shortcomings associated with aging. 

The primary objective of the multi-dose phase I clinical trial is to determine the safety and tolerability of CK-2017357 after multiple oral doses to steady state in healthy male volunteers. The secondary objective is to evaluate the pharmacokinetic profile of CK-2017357 after multiple oral doses to steady state. 

Cytokinetics has initiated Part B of phase 1 trials while Part A is still ongoing. Despite the fact that Part 1 trial remains blinded, investigators could not miss that all the doses given have been  tolerated, including  the dose that produced CK-2017357 blood levels associated with increased skeletal muscle function in preclinical models. 

Part 1 single-dose trial is meant to assess safety, tolerability, and pharmacokinetic profile in healthy male volunteers and determine its maximum tolerated dose and plasma concentration. The objective of the “Part B” trial of phase I trial is to assess the pharmacodynamic effect of CK-2017357 when administered orally to healthy male volunteers. In this trial, the force-frequency relationship of an externally stimulated nerve-muscle pair and its relationship to CK-2017357 plasma concentration will be determined. 

Interested in the trial details Click: http://www.cytokinetics.com/press_releases/release/pr_1257741999. 

CYTOKINETICS PROGRAMS

Cytokinetics has two programs; both deal with life-threatening conditions that have yet to find satisfactory treatments. The first program focuses on developing cardiac myosin activators for heart failure. In this program, the drug, omecamtiv mecarbil, has reached phase 2 clinical trials with promising results. The second program, which is the topic of the above news, is focused on the discovery and development of small molecule sarcomere activators that are expected to boost skeletal muscle (voluntary muscle) contractility. CK-2017357 is the first small molecule sarcomere activator to reach clinical trials. 

How does CK-2017357 work? 

Skeletal muscle contractility is believed to be driven by the sarcomere, which is composed of several key proteins. Myosin, one of the sarcomere’s proteins interacts with a second protein, protein called actin, to convert chemical energy into mechanical force. A set of regulatory proteins, tropomyosin, and three troponin make the actin-myosin interaction dependent on changes in intracellular calcium levels. 

CK-2017357 selectively activates the troponin complex, hence increases its sensitivity to calcium, leading to an increase in skeletal muscle force. The results are encouraging, bringing hope for patients suffering from amyotrophic lateral sclerosis (ALS), myasthenia gravis, sarcopenia, claudication, cachexia, and shortcomings associated with aging.

Market Potential:  

- ALS: Affects between 20,000 and 30,000 people in the United States. The disease is associated with a 3-year mortality rate of 50%. There are no specific effective treatments. 

- Myasthenia gravis: A chronic disease characterized by a defect in the transmission of nerve impulses to skeletal muscles afflicts approximately 60,000 patients in the United States. 

- Cachexia, Is characterized by a drastic and unintentional loss of body mass. It is prevalent in 15%-35% of heart failure patients and in approximately 50% of cancer patients. 

- Intermittent claudication: Cramping pains in the legs caused by peripheral arterial disease. It  impacts between 1million to 3 million people in the United States each year. 

- Sarcopenia: This condition characterized by loss of muscle mass, strength, and function  impacts the lives of around 25-30% of the U.S. population over the age of 65.  

So, the market could be huge. Add to it the heart failure drug market, then we would be talking about billions of dollars in revenues for Cytokinetics when these drugs reach the market. 

Cytokinetics discovered and developed its own breakthrough molecules. Its drugs and their targets are unique and might offer hope for patients suffering from devastating and life-threatening diseases. The rationale behind its treatments is scientifically sound and satisfying and the small molecule drugs developed for skeletal and involuntary muscles have not demonstrated any serious side effects.  

Onyx’ (ONXX) stock decline in the past few months puzzled its shareholders. Nothing that has come in the news in the past year has been bad. On the contrary, a string of promising results was incessantly coming from the clinical trials of the firm’s cancer drug Nexavar on a variety of cancers. Now there are sufficient data to get an approval for other malignancies, including breast  cancers. The drug was first approved for kidney cancer and then for liver cancer and, for a long while, there was no evidence that it would be approved for other cancers. Shareholders, though, did not lose hope. They were satisfied with the drug sales’ growth with sales that were closing on the $1 billion revenues. How come then that at the moment the drug proved to be useful for breast cancer the stock faltered.

Investors first believed that the ONXX decline was a typical phenomenon that briefly occurs when publicly traded firms raise money. Onyx had indeed raised $300 million, but the stock decline was not brief and has not ceased. Taking a deeper look at what the critics were propagating, informed investors found out that, yes, the financing was, indeed, a trigger for the stock decline but not for the sell-off, which was caused by efforts spent towards not letting the stock recover. Negative analysts kept downgrading the firm for various reasons, mostly irrelevant and included hypothesizing that Onyx might spend the vast amount of money it raised uselessly, acquiring a worthless firm!

It was strange that the critics projected pessimism against Onyx’ possible acquisition of a biotech firm that they, themselves, kept advocating. Stranger is the fact that, at the time, nobody had yet learned about any acquisition, as it was not announced. The analysts’ previous take on Onyx was that, besides the cancer drug Nexavar, the firm’s pipeline lacks mid- and late-phase trial. Their best suggestion was that the firm has to increase its value by adding more drugs to its pipeline through acquisition, which is exactly what the company did.

A study was led by Momokazu Gotoh, MD, Ph.D., Professor and Chairman of the Department of Urology and Tokunori Yamamoto, MD, Ph.D., Associate Professor Department of Urology at Nagoya University Graduate School of Medicine demonstrate that stem and regenerative cells from a patient’s own fat tissue used to treat stress urinary incontinence (SUI) demonstrate efficacy in severe cases. The cells in the study were processed using Cytori’s Celution® 800 System during the operative procedure.

The results, reported at the 7th Annual Meeting of the International Federation for Adipose Therapeutics and Science, suggest that the treatment is safe and feasible.  The adipose-derived stem and regenerative cells (ADRCs) were delivered via two distinct formulations. First, they were injected directly into the bladder sphincter with the goal of improving muscle contraction. Secondly, ADRCs were combined with the patient’s own fat tissue to create a cell-enriched bulking agent to improve closure upon sphincter contraction. They were five patients whose stress urinary incontinence  resulted from radical prostatectomy.

The follow-up examinations were thorough and frequent at two, four, eight, and 12 weeks. They were assessed for continence, intraurethral and leak point pressures (measures of urethral sphincter tone) and quality-of-life.  Imaging studies were made.