Gale Scott

	A Netherlands gene therapy company announced that the US Food and Drug Administration (FDA) has given breakthrough therapy status to its experimental product to halt spontaneous bleeding in patients with severe hemophilia B.

	According to unQure, NV, its product called AMT-060 showed in phase 1-2 studies that it was effective at achieving "near cessation of spontaneous bleeding in patients with severe disease at up to 12 months follow-up."

If results hold up, the treatment could be curative, instead of the prophylactic and rescue treatments currently used, according to the company. 

The data were recently presented at the American Society of Hematology Annual Meeting. 

“The FDA’s decision to prioritize and expedite the review of AMT-060 is an important milestone for uniQure and we are committed to working closely with the FDA to rapidly advance our hemophilia B program into late-stage development,” said Matthew Kapusta, chief executive officer of uniQure.

 from the company all five patients in the low-dose cohort, whose bleedings were previously uncontrolled despite being managed with prophylactic therapy, continue to maintain, constant and clinically meaningful levels of Factor IX ( FIX) activity for up to 52 weeks post treatment, resulting in a complete cessation of spontaneous bleedings in the last 14 weeks of observation.

The company added that AMT-060 continued to be well-tolerated with no adverse events that were serious.

Three out of the total of 10 patients (two in the second-dose cohort and one previously reported from the low-dose cohort) experienced mild, asymptomatic elevations of alanine aminotransferase (ALT) and received a tapering course of corticosteroids per protocol. The temporary elevations in ALT were not associated with any loss of endogenous FIX activity or T-cell response to the AAV5 capsid, the company noted.

No patients across either cohort developed inhibitory antibodies against FIX and no patients screened in the study tested positive for anti-AAV5 antibodies.

Hemophilia B is a rare inherited disease that occurs in one of 30,000 live births. Treatment consists of intravenous infusions of plasma-derived or recombinant hFIX to prevent bleeds. If bleeding occurs treatment is daily infusions of these clotting factors.

Articles

The FDA gave a gene therapy for bleeding in hemophilia B breakthrough status.

Breakthrough Designation for Hemophilia Therapy

Stem cell treatment did 37% better than placebo treatment in a group of patients with ischemic heart failure, Timothy D. Henry, MD of Cedars-Sinai Medical Center in Los Angeles, CA and colleagues reported.

In a multi-center trial, investigators used imyelocel-T, an expanded multicellular therapy produced from a patient’s own bone marrow. They extract CD90+ mesenchymal stem cells and CD45+CD14+ auto-fluorescent+ activated macrophages.

The prepared cells were delivered by transendocardial injection using a catheter-based approach.

Patients in the study had ejection fraction of less than 35%, an automatic implantable cardioverter defibrillator and were not well enough for revascularization procedures.

Subjects and controls got either ixmyelocel-T or placebo after undergoing bone marrow aspiration. The procedures were done under anesthesia and the bone marrow was extracted from the posterior iliac crest.

In the treatment group (66 patients) 38% experienced a serious event compared to a rate of 49% in the placebo group (51 patients.)

Ischemic dilated cardiomyopathy is a common condition in patients whose coronary heart disease has progressed, and a leading cause of mortality and morbidity in these patients.

It is also the largest cause of hospital readmissions in the US, the team noted.

The trial, known as ixCELL-DCM, shows the therapy is promising and “should stimulate additional cell therapy trials to further explore the benefit of cell therapy in patients with heart failure,” they wrote.

The study was presented April 4 at the American College of Cardiology's 65th Scientific Session & Expo in Chicago, IL and was simultaneously published in 

Stem cell treatment did 37% better than placebo treatment in a group of patients with ischemic heart failure.

Stem Cell Therapy Has Postive Results for Cardiomyopathy Patients

Could curing heart failure be as simple as administering a one-time outpatient infusion of a gene therapy product?

 researchers presented promising results of a Phase II trial showing that gene transfer treatment of patients with heart failure and reduced ejection fraction was safe and successful in over 90% of patients.

In an interview, Jack Reich, PhD, co-founder and CEO of Renova Therapeutics in San Diego, CA, which plans to market the gene product as “RT-100,” said the patients were treated with an infusion of AC6, a protein found in cardiac muscle cells.

In most heart failure patients this protein is down-regulated in the heart, leaving the organ contracting weakly.

In the trial, an inactivated adenovirus vector encoding human adenylyl cyclase type 6 (Ad5.hAC6) was infused directly into the arteries to the heart during cardiac catheterization.

“Forty percent of the heart cells took it up like a sponge,” Reich said.

In the journal article, lead author Kirk Hammond, MD, co-founder of Renova, and colleagues concluded that the two end points of the study “showed significant between-group differences: (1) AC6 gene transfer increased LV peak −dP/dt (

&thinsp;<&thinsp;.03); and (2) AC6 gene transfer increased EF in participants with nonischemic heart failure (

The AC6 gene transfer “safely increased LV function beyond optimal heart failure therapy through a single administration,” the team wrote.

The treatment, if it continues to prove safe and effective, could easily be scaled up, Reich said. “This is absolutely a therapy for the masses,” he said.

“It works on anyone who has heart failure, people with big floppy hearts—some of the patients in the study had class 4 heart failure and a life expectancy of three to six months ,” but recovered after treatment, Reich said.

He predicted the therapy would also be “very inexpensive.”

To be included in the study, patients had to have a left ventricular ejection fraction of less than 40%.

The average for the 42 patients who received AC6 therapy was 30%, Reich said.

“These are people who can’t climb a flight of stairs,” he said.

There was a high success rate, with 9.5% of patients being readmitted to a hospital within a year of treatment vs. 28.6% of the placebo group.

Large trials in the US and Europe are next, he said.

The research was funded in part by the National Institutes of Health.

There have been promising results in a Phase II trial showing that gene transfer treatment of patients with heart failure and reduced ejection fraction was safe and successful in over 90% of patients.

Promising Gene Therapy for Heart Failure

Anti-B-cell therapy has been shown to help patients with primary Sjogren's Syndrome (PSS.) A research team in the UK looked at how well rituximab (Rituxan/Genentech) improved the condition's symptoms of fatigue and dry mouth. 

Reporting at the American College of Rheumatology Annual Meeting in San Francisco, CA, Simon Bowman o university Hospital Birmingham, Birmingham, UK and colleagues recruited subjects from 25 rheumatology clinics in the UK. 

All received pre- and post-infusion corticosteroids and either placebo of rituximab.The primary endpoint of the study was the proportion of patients achieving 30% reduction in either fatigue or oral dryness at 48 weeks. 

The also looked at fatigue and oral dryness separately, global assessment of PSS activity, pain, ocular and overall dryness, flow of saliva and tears, and quality of life. 

There were 133 patients, with a mean age of 54, nearly all of them women. 

Only 24 of 61 patients getting the drug regimen achieved the endpoint, barely more than the 21 of 56 patients who achieved the endpoint while getting a placebo. 

The only outcome on which patients getting the drug scored higher was salivary flow. There were more adverse events re ported in total for the drug group, but none were serious. 

The group concluded that the trial, while the largest randomized trial of a biologic therapy in PSS, was disappointing in its results. "No improvement in symptoms was seen in the rituximab arm, but [there was] modest benefit for rituximab in salivary flow. 

The researchers will report their results on Nov. 10 at the meeting. 

 A research team in the UK looked at how well rituximab (Rituxan/Genentech) improved the Sjogren's Syndrome symptoms of fatigue and dry mouth. 

Anti-B Cell Therapy Helps Little with Some Sjogren's Syndrome Symptoms

A group of New Yorkers seeking rejuvenation with sheep cell injections at a German clinic came home with Q fever instead.

This "live cell therapy" is not available in the US, according to the US Centers for Disease Control and Prevention. It can be dangerous, and, contrary to promises by German practitioners, the treatment ended badly for a five New York State residents who last year came down with Q fever after traveling to Rhineland-Palatine where they got the sheep shots. 

 for the German Centre for Fresh Cell Therapy says the treatment helped “Pope Pius XII, Emperor Hirohito, Emperor Haile Selassi, King Ibn Saud, Konrad Adenauer, Charlie Chaplin,” (all of whom are dead) and many more.

The CDC, reporting in the current issue of 

 said the infections came to light through the German physician's center. After being informed that a traveler from Canada had been stricken with Q fever after getting the shots, the physician notified the five New Yorkers that they could be infected. The flock from which the cells were obtained had earlier been linked to human cases of Q fever there. 

When located by US health officials, three travelers had already sought medical treatment and two said they had been ill but not gone to a doctor. They were tested and the results were analyzed by the New York State Department of Health. All were positive for the organism that causes Q fever, 

All had received fetal sheep cells. Investigators learned that another five to 10 people had also been in the group that traveled to Germany to get the injections but were lost to followup, the CDC said.

The patients who became ill, ages 59 to 83, included one with preexisting atrial fibrillation and kidney stones, one with Parkinson disease, and one with multiple sclerosis. All had fatigue, sweats, and difficulty sleeping. Symptoms lasted as long as 90 days. In interviews with health officials they said that they were part of a group that had traveled to Germany for the injections for the past five years “to improve their general health and vitality.”

The live cell treatments were developed in the 1930s by German practitioner Paul Niehans. The practice can involve injections of cells from organs, glands, and fetuse of non-human animals. The cells can be taken from sheep, cows, and sharks, the CDC said, referring to information at a California 

On that site the advice is that “shark embryo cells seem to be vastly superior to sheep embryo cells.”

The CDC notes that no published clinical evidence has ever supported the claims, though the "live cell" treatment  has been advertised as successful for erectile dysfunction, neurological ailments, and conditions involving the heart, kidney, lungs, liver and endocrine system. “Serious adverse events have been reported” including death, the CDC said.

Live cell therapy--an unproven treatment involving injections of live fetal cells from sheep--is legal in Germany. A group of New Yorkers who went there to make them younger and healthier got Q fever instead, the CDC reports.

Live Sheep Cell Injections? CDC Says 'Bah'

San Diego-based Renova Therapeutics reported that its RT-100 gene therapy treatment for patients with reduced left-ventricular ejection fraction congestive heart failure (CHF) is proving safe and effective. 

The treatment involves delivering a therapeutic gene encoding adenylyl cyclase type 6 (AC6) directly into the heart via a modified adenovirus. 

It is a single-dose procedure done in an outpatient setting. 

Reporting on the results of a multi-center, placebo-controlled Phase 2 trial, company co-founder Kirk Hammond, MD, said the therapy showed a strong safety profile and clear dose response. 

The study assessed the safety of various doses of RT-100 in people with CHF.

Preliminary results showed no specific safety concerns and no unexpected changes in blood pressure or heart rate, the company said. 

The researchers also found "statisically meaningful improvements from baseline" at 12 weeks in key primary and secondary endpoints. Those included left ventricular ejection fraction and patients' reports of quality of life. 

Both results were found in two groups of subjects getting the highest doses of the product.

These patients also showed significant improvements over placebo in negative dP/dt, the company said. 

The study involved 56 patients in seven US medical centers.

The trial was funded in part by the National Institutes of Health. 

The positive news on the trial was in marked contrast to that about the last gene therapy to be touted as a breakthrough in treating CHF. 

In April, 2015, San Diego-based Celladon announced that its potential gene therapy Mydicar had failed to reach its primary and secondary endpoints and that researchers could not prove efficacy. 

That trial involved a different gene, SERCA2A. Its trial was being conducted under a breakthrough therapy protocol and was funded in part with a $53 million infusion of capital from three big pharma companies. 

California researchers report good results in a phase II study of a gene therapy for congestive heart failure. The news comes five months after Celladon's Mydicar gene therapy for CHF failed to meet its trial's endpoints. 

Promising Results on Gene Therapy for Congestive Heart Failure

Treating patients who have relapsing-remitting multiple sclerosis (RRMS) with autologous hematopoietic cell transplantation (HCT) has worked for most patients based on an interim report 3 years into a study. But the therapy has risks that critics say outweigh the benefits.

 Richard Nash, MD of the Colorado Blood Cancer Institute in Denver, CO, and colleagues found they could achieve sustained remissions in early RRMS patients with high-dose immunosuppressive therapy (HDIT) and HCT. In an interim report on their ongoing multi-center HALT-MS study the researchers said 24 patients with RRMS got the treatments. At 3-year followup, 78.4% of these patients had had no MS attacks or developed any new MS lesions.

The therapeutic intervention consisted of collecting peripheral blood stem cells from patients, then treating them with high doses of carmustine, etoposide, cytarabine, and melphalan. They also go rabbit antithymocyte globulin before their stem cells were reintroduced.

The reasoning behind the treatment is that in MS immune cells migrate into the central nervous system. The chemotherapy agents used are meant to wipe out these intruders. Then, by re-introducing hematopoietic cells, doctors reset the patient’s immune system.

In the study, 24 patients received treatment. The median time period since MS diagnosis was 4.9 years. Patients were aged 27 to 53 and 68% were female.

But among the adverse events that occurred were 2 suicide attempts and 2 deaths. In all 5 patients failed treatment. On the positive side, event-free survival was 82.8% at 2 years, and 78.4% at 3 years.

The authors conclude that HDIT/HCT treatment “induced remission of MS disease activity for up to 3 years in most participants.” For that reason, it may “represent a therapeutic option for patients with MS in whom conventional immunotherapy fails, as well as for other severe immune-medicated diseases of the central nervous system,” despite the adverse events reported. The full study will be completed when patients have been followed for 5 years.

, Mateo Paz Soldan, MD, PhD, and Brian Weinshenker, MD were unconvinced that the HDIT/HCT treatment should become a standard therapy. “Patients and physicians should expect that aggressive and expensive therapy such as HDIT followed by HCT should perform better than any alternative treatment,” they wrote. “The jury is still out regarding the appropriateness and indications of HCT for MS.”

Treating patients with relapsing-remitting multiple sclerosis (RRMS) with autologous hematopoietic cell transplantation (HCT) has worked for most patients based on an interim report 3 years into a study. But the therapy has risks that critics say outweigh the benefits. 