Study of Potential Therapy for Congenital Muscular Dystrophy Gets Boost from FDA

msnewstodayStudy of Potential Therapy for Congenital Muscular Dystrophy Gets Boost from FDA

August 31, 2016

By Carolina Henriques

http://musculardystrophynews.com/2016/08/31/fda-grant-supports-clinical-trial-of-congenital-muscular-dystrophy-treatment-omigapil/

Santhera Pharmaceuticals announced that it has received a $246,000 grant from the U.S. Food and Drug Administration (FDA) to support its ongoing Phase 1 clinical trial evaluating omigapil as a potential treatment for children and adolescents with congenital muscular dystrophy (CMD).

The study, called CALLISTO (NCT01805024), is assessing the pharmacokinetics, safety, and tolerability of omigapil in ambulatory and non-ambulatory children, ages 5–16, with either of two CMD subtypes (COL6-RD or LAMA2-RD). About 20 eligible patients are currently being recruited; more information is available on the study’s clinical trials.gov website.

“We are delighted that the FDA has awarded us this prestigious and highly competitive grant in support of our CALLISTO trial in CMD,” Thomas Meier, Ph.D., chief executive officer of Santhera, said in a press release. “With this award the FDA emphasizes the need for a therapy for CMD and the contribution of the CALLISTO trial to the development of an effective treatment.”

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CMD is a clinically distinct group of inherited neuromuscular diseases that manifests with an early onset of symptoms that include weakness, contractures, elevated creatine kinase levels, an inability to stand or walk, eating difficulties, and respiratory insufficiency.

Omigapil is a deprenyl-analog with anti-apoptotic properties that binds to GAPDH. This interaction leads to its inhibition, and is thought to underlie the compound’s observed anti-apoptotic effect. In animal models of CMD, omigapil was seen to prevent cell death, reduce body weight loss and skeletal deformation, and to improve locomotive activity.

The proposed treatment was given Fast Track designation by the FDA for the treatment of CMD in May, and has previously been granted Orphan Drug Designation for the same indication in Europe and the United States. Santhera’s grant award came from the FEA’s Office of Orphan Products Development.

“As the leading organization representing the interests of patients with CMD, we are very pleased that the FDA recognizes the need to advance medical research in this orphan disease. With currently no effective treatment available for patients, the CALLISTO trial offers hope to patients with this devastating disease,” said Patrick May, CureCMD’s president.

The trial is being conducted in collaboration with the U.S. National Institutes of Health (NIH) under the leadership of Professor Carsten Bönnemann and Dr. Reghan Foley, with the National Institute of Neurological Disorders and Stroke (NINDS). Study completion is expected in early 2017.

Omigapil was developed by Novartis, and Santhera holds an exclusive worldwide license for its development as a treatment for congenital muscular dystrophy.

Escape velocity? Bioblast phase II could open door to remedy in rare OPMD

BIOWORLD TODAY 

MARCH 17, 2016

THE DAILY BIOPHARMACEUTICAL NEWS SOURCE

BIOTECH’S MOST RESPECTED NEWS SOURCE FOR MORE THAN 20 YEARS

VOLUME 27, NO. 52

TRIAL TO VERIFY THIS YEAR

Escape velocity? Bioblast phase II could open door to remedy in rare OPMD

By Randy Osborne, Staff Writer

Bioblast Pharma Ltd. CEO Colin Foster told BioWorld Today “it would not be unreasonable to think” that regulators could deem pivotal the upcoming phase IIb trial with trehalose in oculopharyngeal muscular dystrophy (OPMD), but the company doesn’t count on that. “We’re looking forward, recognizing that we [probably] have to do a phase III study,” he  said.

 

Shares of New Haven, Conn.-based Bioblast (NASDAQ:ORPN) closed Wednesday at $4.20, up $1.56, or 59 percent, having traded as high as $7.95 after the firm disclosed phase II data from its HOPEMD trial testing the disaccharide trehalose, known for its ability to stabilize intracellular and intranuclear proteins. The experiment aimed to learn about safety and tolerability – trehalose passed in those departments – but also included secondary endpoints to see if the drug improved, or at least prevented worsening, of markers in rare disease OPMD. It rang bells there, too.

An inherited myopathy, OPMD is characterized by dysphagia (difficulty in swallowing), eyelid drooping, or ptosis, as well as loss of muscle strength and weakness. Specifically, it’s a polyalanine-mutation disease with onset around middle age.

“On some highly consequential proteins associated with normal muscle homeostasis, you’ve got a particular protein that ends up having too many alanines stuck on the back,” Foster said, which “creates just a mess. It’s almost like a dust bunny under your bed.” Proteins can’t fold properly, leading to symptoms, and patients become emaciated because they are unable to eat normally.

“They’ve lost the reflex to get rid of food that goes down their windpipe,” he said, and suffer repeated bouts of aspiration pneumonia, which can lead to  death.

“It’s an insidious, one-way disease,” Foster said. “For the muscle weakness, there’s nothing. You’re stuck with it.” Surgery may help swallowing. “Literally, [surgeons] seek to expand the size of your throat, allowing food to plop down more easily into the esophagus.” But the benefits only last about 15 months on average.

“That gives you an idea how accelerated this disease is, even on the dysphagia side,” he said, noting “a tremendous amount of apathy among the undiagnosed. They know what the future holds. I got a call from a guy on Long Island the other day” whose father is afflicted. The son “doesn’t want to be like that, but he’s already got symptoms that are going to set him on the same course as his dad. People are looking for solutions, for sure.”

In the open-label trial, data from which were reported Wednesday at Myology 2016, a muscle conference in Lyon, France, 25 patients with OPMD clinical dysphagia and muscle weakness were enrolled at two centers in Canada and Israel.    All have completed 24 weeks of weekly treatment, and Bioblast reported improvements vs. baseline in multiple secondary efficacy endpoints related to dysphagia along with muscle strength and function.

 

POTENTIAL TAKEOUT: ANALYST

The dysphagia endpoints were the timed cold water  drinking

 

test (80 mL) for all sites, the nectar (80 mL) and honey (80 mL) timed drinking tests at the Canadian site, and the Penetration Aspiration Score as measured by video fluoroscopy   (VFS-
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PAS), a radiographic technique to determine the severity of swallowing difficulties and risk of aspiration. One patient- reported, swallowing quality-of-life questionnaire (SWAL-QOL) specifically developed for patients suffering from swallowing problems was employed to assess the degree to which patients felt that their swallowing capability improved with  treatment.

A mean reduction in time to complete the cold water drinking test of 31.8 percent turned up vs. baseline (n=23). In the nectar and honey timed drinking tests, time to complete was reduced by 43.8 percent and 46.6 percent, respectively (n=11). Out of the 11 patients in Canada whose scores were evaluated in the per- protocol analysis of the VFS-PAS, six patients improved (54.5 percent), two showed stabilization (18.2 percent), and three deteriorated (27.2 percent). Due to deviations from protocol and deficient radiological procedures, the VFS-PAS tests from the Israel cohort were excluded from the final analysis. With   respect to the SWAL-QOL questionnaire, there was a 12.7 percent (n=24) improvement vs. baseline with the mean total symptom severity score increasing from 43.2 to  48.7.

 

As measured quantitatively by a digital hand-held dynamometer,  a mean increase was recorded in lower body-muscle strength compared to baseline in knee extension of 15 percent (n=22)

and foot dorsiflexion of 22.4 percent (n=22). Hip flexion did not materially change (1.3 percent deterioration, n=21). For the upper-extremity strength tests, arm (bicep) flexion increased on average 17.9 percent (n=22), and shoulder abduction by 11.4 percent (n=22).

 

The 30-second arm-lift test showed a 16 percent increase in the number of completed tasks (n=20) at 24 weeks of  treatment vs. baseline, while the 30-second, sit-to-stand test showed a

16.6 percent increase (n=21). In a standard, four-stair climbing test, the results didn’t change much (1.5 percent deterioration, n=21).

 

“When we talk to our neurologists, they say [hip flexion] one of these things that’s going to be very difficult to change,” Foster said. The stair-climbing scores may not provide a good picture “because, in that particular test, you’re not really testing single- muscle strength performance” – a group of muscles is involved. Bioblast’s phase IIb trial is expected to start around mid-year, he said.

The long shot of approval based on the pair of phase II studies could pan out “if we design the study appropriately and execute well and have some very good data at the end of it, confirming the positive effect [or] perhaps even accentuating the positive effect, because people won’t be compared to baseline but to people who are on placebo,” he said, estimating the  phase

IIb will enroll “between 40 and 80 patients. That’s sort of the realm. It’s a very manageable trial.”

Starting coverage in January and calling Bioblast “underrated,”

 

Rodman & Renshow analyst Raghuram Selvaraju estimated peak sales of trehalose in OPMD alone at $600 million. The drug is also in phase II development for spinocerebellar ataxia type 3. Merger-and-acquisition transactions “in the orphan sector involving firms with narrower pipelines than Bioblast have taken place at much higher valuations,” he wrote in a research report, pointing to the buyout of Lexington, Mass.- based Synageva Biopharma Corp., a single-product orphan drug company, by Alexion Pharmaceuticals Inc., of Cheshire, Conn., for $8.4 billion, which happened before Synageva won approval for its sole clinical asset, Kanuma (sebelipase alfa) for lysosomal acid lipase deficiency. (See BioWorld Today, May 7, 2015, and Dec. 9, 2015.)

OPMD is known to affect about 6,000 people in the U.S. “We fully expect, knowing how these things happen, there are probably two to three times that number who are undiagnosed, and frankly, some market research tells us the number could even be higher than that,” Foster said.

Efficacy and speed were two things that together made up “a little bit of a eureka moment,” in the currently reporting trial, he added, but Bioblast needs to “prove it the old-fashioned way” with the phase IIb, double-blind, placebo controlled study. “I’m feeling very good,” he said. “We’ve got something.” //

 

BioBlast submits Phase II interim data for Cabeletta in OPMD to two conferences – CEO

BioPharmInsightBioBlast Pharma (NASDAQ:ORPN) has submitted its Phase II interim data for Cabaletta (intravenous trehalose) in opculopharyngeal muscular dystrophy (OPMD) to the American Academy of Neurology (AAN) annual meeting and the 5th International Congress of Myology for presentation, said CEO Colin Foster. The AAN conference takes place 15­21 April 2016 in Vancouver, Canada whilst Myology 2016 takes place 14­18 March 2016 in Lyon, France.

The company announced positive interim results for Cabaletta on 27 October. Ten out of 12 patients (83.3%) were observed to stabilize or improve on an efficacy endpoint, the Penetration Aspiration Score, related to dysphagia (difficulty in swallowing), as measured by Video Fluoroscopy (VFS­PAS). There was a statistically significant improvement in the timed drinking test, a swallowing quality­of­life symptom score, as measured by the SWAL­QOL questionnaire. Patients also showed a statistically significant improvement in their lower extremities’ muscle strength versus baseline, and demonstrated numerical improvement in other muscle strength and function tests.

The company is now in the process of planning a Phase III trial for early 2016 contingent on FDA discussions , said Foster. There will be three sites in the Canada as well as six in the US enrolling around 80 patients in total, he noted. The primary endpoint will be Penetration Aspiration Score as measured by VFS­PAS, he added.

At the end of 2Q15, BioBlast had USD 26m in cash which should see the company through the Phase III trial, said Foster. In the future the company may look to business development partnerships or a capital raise in order to develop its other drug candidates, he said, declining to comment further on these points. BioBlast has recently hired a chief corporate development officer to assist the company with M&A and business development, Foster added.

OPMD is an inherited myopathy characterized by dysphagia and the loss of muscle strength, and weakness in multiple muscles of the body. Symptoms generally appear in mid­life and get worse over time. As the dysphagia becomes more severe, patients become malnourished, lose significant weight, become dehydrated and suffer from repeated incidents of aspiration pneumonia.
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Cabaletta is a chemical chaperone that protects against pathological processes in cells. It has been shown to reduce pathological aggregation of proteins within cells in several diseases associated with abnormal cellular­protein aggregation as well as acting as an autophagy enhancer, according to the company website. BioBlast is also investigating Cabaletta in spinocerebellar ataxia type 3, said Foster.  A Phase II trial is underway in Israel and is fully enrolled with an expected December completion date, he added.

The company is opportunistic regarding in­licensing additional orphan disease drug candidates that fit strategically with the company’s current platforms, said Foster. A candidate with clinical proof of concept would be preferred, however, if the data is good enough, preclinical candidates may be considered, he added.

BioBlast’s market cap is USD 70.44m.

by Hamish McDougall in London

BioBlast sets sights on PhIII after efficacy prompts early halt of mid-stage study

FierceBiotech2

 

 

October 29, 2015 | By Nick Paul Taylor

http://www.fiercebiotech.com/story/bioblast-sets-sights-phiii-after-efficacy-prompts-early-halt-mid-stage-stud/2015-10-29
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BioBlast Pharma ($ORPN) has posted a glimpse at the data that prompted it to wrap up a Phase II trial after enrolling just one-third of the targeted number of patients. And while there is very little data available publicly to support BioBlast’s optimism, the company thinks it has a strong enough hand to start discussing a Phase III trial with the FDA.

BioBlast CEO Colin Foster
BioBlast CEO Colin Foster

BioBlast also reported improvements in timed drinking tests, swallowing quality of life symptom scores and muscle strength, leading it to conclude that the ethical thing to do would be to wrap up the study early and power toward Phase III. However, in doing so, BioBlast has left itself with a set of data that has some limitations. While BioBlast enrolled 25 patients before halting recruitment, it only has Penetration Aspiration Scores for 12 participants because of failings at the Israeli trial site. The failings means BioBlast lacks Penetration Aspiration Scores for seven patients enrolled in Israel.Tel Aviv, Israel-based BioBlast stopped the open-label trial early on the basis of an interim analysis of 25 patients with oculopharyngeal muscular dystrophy (OPMD). The genetic disorder causes muscle wasting that ultimately renders people unable to swallow. To gauge whether its drug, Cabaletta, can help treat these symptoms, BioBlast x-rayed the mouths and throats of participants to see how deep material passed before and after they received the drug. Of the 12 patients assessed, 6 improved and 4 stabilized on the Penetration Aspiration Score 24 weeks after treatment with Cabaletta.

BioBlast also reported improvements in timed drinking tests, swallowing quality of life symptom scores and muscle strength, leading it to conclude that the ethical thing to do would be to wrap up the study early and power toward Phase III. However, in doing so, BioBlast has left itself with a set of data that has some limitations. While BioBlast enrolled 25 patients before halting recruitment, it only has Penetration Aspiration Scores for 12 participants because of failings at the Israeli trial site. The failings means BioBlast lacks Penetration Aspiration Scores for seven patients enrolled in Israel.

BioBlast Skips To Phase III In Rare Form of Muscular Dystrophy

Biotech plans Phase III program for I.V. sugar formulation Cabaleta in oculopharyngeal muscular dystrophy, after reporting limited, So, this medicine has become a order viagra http://raindogscine.com/?attachment_id=44 also with the hands of some online pharmacies. But, there are personalities levitra sale raindogscine.com who are still okay if the problem is still there in their life. Our bodies are open to the air and this reaction produces http://raindogscine.com/tag/documental-2/ levitra 40 mg huge amounts of heat which in turn can cause lightening. Silagra improves the erection cialis de prescription problems in the body. proof-of-concept data for the rare, debilitating swallowing disorder.

Click Here to read the full article.

Bio Blast Pharma reports promising data on muscle wasting drug

Reuters

Bio Blast Pharma Ltd said its lead experimental drug showed signs of being effective in treating patients with a rare muscle wasting disorder, besides also hitting the main goals of safety and tolerability.

The company said the experimental drug, Cabaletta, hit multiple efficacy endpoints during a mid-stage trial on patients suffering from oculopharyngeal muscular dystrophy, according to interim results from study.

Oculopharyngeal muscular dystrophy is a rare disease where patients develop swallowing difficulties, which could lead to death in severe cases.

Bio Blast said the drug improved patients’ muscle function while also reducing difficulty in swallowing.

Kamagra Oral prices of viagra Click Here Jelly is a more reasonable alternative, which is the reason it is getting in to the market for its high performance and lower cost. According to a recent research, less than 10% men with erectile condition? If you are thinking to go with basic latex ones and not the variants with dots, else it’ll just beat the primary reason (some even have patterns inside). tadalafil sales Be willing to viagra uk understand where they are coming after me I can only assume that normal membership is dropping and they are going to give an overview of some of the most popular ED medications in the world. The cheap india viagra GreenLight PVP Laser Procedure is the latest technological innovation in the treatment of prostate gland enlargements. The company said it would discuss results from this study and a second mid-stage study with the U.S. Food and Drug Administration before it started a late-stage study.

Bio Blast is also testing the drug as a treatment for spinocerebellar ataxia type 3, another genetic condition that affects the nerves in the brain.

Up to Monday’s close of $5.04, the Israeli company’s U.S.-listed shares have lost a little over half their value since they went public in July last year.

(Reporting by Vidya L Nathan in Bengaluru; Editing by Savio D’Souza)
Read more at Reuters

http://www.reuters.com/article/2015/10/27/us-bio-blast-pharma-study-idUSKCN0SL14O20151027#MrVYQdKUvWOoXyXL.99

BioBlast Scant Data Links Drug to Improved Swallowing in Patients

TheStreethttp://www.thestreet.com/story/13338729/1/bioblast-scant-data-links-drug-to-improved-swallowing-in-patients.html

By Adam Feuerstein

| 10/27/15 – 06:05 AM EDT

Oculopharyngeal muscular dystrophy (OPMD) is a rare, genetic, muscle-wasting disease that mostly strikes people in their 40s and 50s. The first symptoms of the disease are often an inability to keep the eyelids open, coupled with difficulty swallowing. As the muscles in the face and throat weaken over time, patients lose the ability to properly swallow food or water. In severe cases, OPMD patients die from choking or from infections caused by food getting into the lungs.

There are no drugs approved to treat OPMD currently, but on Tuesday, an Israeli biotech company, BioBlast Pharma (ORPN) , disclosed partial results from a small, mid-stage clinical trial showing a common sugar used for years to preserve frozen food and as a non-active stabilizer in other drugs might improve the swallowing ability of OPMD patients.

The sugar-turned-drug being developed by BioBlast is called Cabaletta. The phase II open-label study in OPMD was stopped early — only one-third of the planned number of patients were enrolled — because the Cabaletta data seen to date were so promising it was unethical to continue, said Dalia Megiddo, BioBlast’s co-founder and chief development officer, in an interview Monday night.

BioBlast intends to meet with regulators at the U.S. Food and Drug Administration seeking clearance to advance Cabaletta into a phase III study in OPMD patients.

Megiddo and BioBlast CEO Colin Foster paint a very optimistic picture of Cabaletta’s potential as an effective treatment for OPMD, but the data announced Tuesday are scant, cherry picked and hardly conclusive.

BioBlast shares closed Monday at $5.06 and with an overall market value of $74.9 million. The stock has lost 21% of its value so far this year.

The original design of the phase II study called for 74 patients with OPMD to be treated with weekly, intravenous injections of Cabaletta for six months. BioBlast only enrolled 25 patients into the study at two hospitals, one in Israel and the other in Canada. The results disclosed Tuesday came from an unplanned, interim analysis conducted on Sept. 1.

Apart from this the pill has been approved by FDA and so one can make use of cheapest levitra respitecaresa.org. Lots of men are struggling for curing their impotency or erectile dysfunction has made man to stay sexually incapable by infecting the concerned mechanism. cialis generika 10mg What are the principles of massages? The principle of massage manipulation therapy is viagra discount india to dredge the channel. Still, in many cases, conception doesn’t happen, and the couples are required to commander viagra seek for the therapy, which you are going to find in this article. Since difficulty swallowing and ingesting food into the lungs puts OPMD patients at the greatest risk, BioBlast relied on a moving x-ray of the mouth and throat to measure if Cabaletta could improve the ability of patients to swallow (or avoid having food get into the airway).

On this efficacy endpoint, known as the Penetration Aspiration Score, BioBlast says 10 of 12 patients, or 83%, showed stabilization or improvements in swallowing ability following six months of treatment with Cabaletta.

BioBlast enrolled 25 patients into the study, so why only results in 12 patients? In seven other patients treated in Israel, the moving x-ray taken at baseline didn’t work, so BioBlast excluded them from the analysis. One patient died during the study. The data from the remaining five patients have not yet been analyzed, said Megiddo.

The mean and median improvements in Penetration Aspiration Score were not disclosed. Megiddo says these data are unimportant because the study enrolled so few patients. Instead, the difference in swallowing ability of individual patients at six months was measured against their own baseline scores.

The Penetration Aspiration Score is an eight-point scale, with the lower score correlated to better swallowing ability. Megiddo says four patients with stabilized swallowing had the same Penetration Aspiration Score at six months as they did at baseline. The six patients with improved swallowing after six months reduced their Penetration Aspiration Score by 1 or 2 points. The study had no control arm by which these results could be compared.

BioBlast intends to use the Penetration Aspiration Score as the primary endpoint of its phase III study.

Other measures of swallowing ability and muscle function used in the phase II study yielded mixed results in different and inconsistent numbers of patients.

Cabaletta is a form of the natural sugar trehalose, already approved by FDA as a food-safe ingredient. Trehalose is also used a non-active stabilizing agent in protein-based cancer drugs like Avastin and Herceptin. As a sugar, trelahose is broken down in the small intestine, so Cabaletta is formulated as an intravenous injection to bypass the intestine and deliver a therapeutic dose more effectively to muscles and nerve cells.

The genetic mutation which causes OPMD creates an unstable protein, PABPN1, which then collects in muscle cells instead of being removed. Bioblast believes trehalose, formulated as Cabaletta, acts as a stabilizer for the misshapen PABPN1 proteins, preventing the proteins from accumulating together and helping rid them from the body.

BioBlast has no composition of matter patents on Cabaletta since trehalos is a naturally occurring sugar. The company is developing Cabaletta based on method-of-use patents protecting the intravenous formulation for use as a drug.