Prana doses 1st patients in Phase 1 Parkinson’s trial

• Prana enrols and doses its first cohort of healthy volunteers in its Phase I clinical trial
• Evidence supports activity of PBT434 to prevent α-synuclein accumulation and neuron loss in experimental animal models of parkinsonian diseases
• Transition to human trials is a milestone for the Company building on its well-established scientific foundations
• Highly experienced drug development team, based in San Francisco, leading the program

Prana Biotechnology Ltd (ASX PBT: NASDAQ PRAN) is pleased to announce the first cohort of volunteers in its Phase I clinical trial have been administered PBT434, an experimental drug under investigation for the treatment of Parkinsonian diseases.

The trial conducted in Melbourne, Australia is recruiting and dosing healthy adult and elderly volunteers, to ascertain the optimal drug dose. The primary goal of the Phase 1 clinical trial is to demonstrate the safety and tolerability of PBT434, with a secondary endpoint of pharmacokinetic measures assessing and understanding how the drug is absorbed and metabolised in the human body.

PBT434 is the first of a new generation of small molecules designed to inhibit the aggregation of alpha(α)-synuclein and tau, critical intracellular proteins that are implicated in neurodegenerative diseases such Parkinson’s disease and atypical parkinsonism. PBT434 has been shown to reduce the pathological accumulation of these proteins in animal models of disease and has excellent potential to treat various forms of atypical parkinsonism, such as Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP).

Prana’s Chief Medical Officer and Senior Vice President, Clinical Development Dr David Stamler, MD, said: “The first human administration of PBT434 is a major milestone for Prana. MSA and PSP are devastating diseases with no effective treatments and this is an important first step in developing a therapy for individuals with these diseases.”

The development program for PBT434 is being led by Dr Stamler from Prana’s San Francisco office. Dr Stamler and his team are highly experienced and have brought several new drugs to market, including deutetrabenazine for the treatment of Huntington’s disease chorea and Tardive dyskinesia, both of which were approved by the U.S. Food and Drug Administration (FDA) in 2017. This was the second neurological agent that Dr Stamler has led through the approval process with the FDA.

https://yhoo.it/2lV6ba0

Zynerba shifts gears to save cash after trial fail

• Zynerba Pharmaceuticals on Thursday announced negative topline results from a Phase 1 safety and dosing study of its transdermal tetrahydrocannabinol patch ZYN001, sending shares down as much as 15% in early morning trading.
• The results showed the patch was unable to achieve target blood levels of 5 to 15 ng/ml of tetrahydrocannabinol. There were no serious adverse events or discontinuations during the study.
• Based on the findings, Zynerba has chosen to shift its focus to ZYN002, which is being developed in Fragile X syndrome, developmental and epileptic encephalopathy and adult refractory epilepsy.

Zynerba made the decision to shift resources away from ZYN001 to conserve cash. The company now has cash and equivalents of about $52 million, and expects this will sustain operations through the second half of 2019.

Had ZYN001 delivered, the drug was expected to start a Phase 2 study in Tourette’s syndrome. Those plans have now been scrapped.

“The miss raises some question marks about efficacy of the transdermal delivery system and leaves ZYN002 as the company’s sole clinical asset, which has always accounted for our entire valuation,” wrote Jefferies analyst Biren Amin in a Thursday note to clients.

The company will now try to carry ZYN002 over the finish line. But with limited resources and a number of failures in the drug’s past, it will be a difficult task. Last summer, the company announced the drug failed in a mid-stage study for patients with adult epilepsy and focal seizures.

ZYN002, a synthetic transdermal cannabidiol gel, also failed to demonstrate a statistically significant reduction in knee pain for osteoarthritis patients last summer.

The movement comes after competitor GW Pharmaceuticals late last month won Food and Drug Administration approval for its cannabis-based epilepsy treatment Epidiolex (cannabidiol). While this marked the approval of the first plant-derived cannabis-based drug, the FDA was quick to point out that the data supporting approval of Epidiolex was unique and does not support the approval of any other cannabinoids.

https://bit.ly/2MQxca5

Gilead JAK inhibitor may be key to turnaround: Jefferies

Gilead Sciences is eagerly awaiting phase 3 data for its rheumatoid arthritis drug filgotinib in the next few weeks that could be an antidote for the biotech’s hepatitis C hangover.

That’s according to analysts at Jefferies, who see JAK inhibitor filgotinib as a $2 billion to $3 billion product for Gilead if the pivotal data show comparable efficacy to current drugs in the class, led by Pfizer blockbuster Xeljanz (tofacitinib), along with a clean safety profile.

Both Xeljanz and Eli Lilly’s recently approved Olumiant (baricitinib) are saddled with black-box safety warnings that could give Galapagos-partnered filgotinib a chance to quickly catch and possibly overtake its rivals.

Data from the FINCH-2 trial of filgotinib in RA patients who have failed biologics are due imminently and, if positive, could set up another phase 3 win in ulcerative colitis. The latter represents another $2 billion-plus market for the drug, say the analysts in a research note.

They suggest filgotinib’s greater JAK1 selectivity means it is less likely to affect platelets than its rivals, and so could have less risk of clotting side effects. And as it doesn’t appear to decrease hemoglobin levels and natural killer cells it could be less likely to cause other toxicities such as low red cell counts and infections.

That said, if all goes as hoped and filgotinib hits the top-line objective of a 20% to 30% improvement on the ACR 20 symptom scale after 12 weeks—depending on the dose—it could still be the fourth JAK inhibitor to reach the market for RA, behind Xeljanz, Olumiant and AbbVie’s much-touted upadacitinib.

“Filgotinib could be ‘best in class’ although fourth to market—and we acknowledge rebating will also be key here in the competitive market, as we note the street currently already appears unclear about how it will play out, hence not enough credit yet for the franchise.”

Of course, Gilead is looking for multiple new growth drivers now that sales of its hepatitis C franchise are in freefall, and filgotinib isn’t its only iron in the fire. Jefferies also points to nonalcoholic steatohepatitis (NASH) candidate selonsertib that is due to generate results in the first half next year, although it’s worth noting NASH is viewed as a tricky indication with a lot of companies in the race to market, so it’s a high-risk project.

And while there is a lot of bullishness about the biotech’s pipeline at the moment, there’s also a lot riding on both of these trial read-outs, and sentiment toward the company could be quickly dented if all doesn’t go to plan.

Nevertheless, Jefferies says Gilead “remains our top large-cap idea for a turnaround story and the most under-owned large cap in our coverage universe.”

Their turnaround projection is based in the near term on strong demand for three-in-one HIV drug Biktarvy, which has yet to make any meaningful contribution, as well as gradual increases for CAR-T therapy Yescarta and a bottoming out for hepatitis C product sales.

https://bit.ly/2NuPZc3

Bristol gets expanded pediatric label for leukemia med in Europe

Approval includes the first powder for oral suspension formulation of a tyrosine kinase inhibitor developed for administration in pediatric patients

Bristol-Myers Squibb Company (NYSE:BMY) today announced that the European Commission (EC) has expanded the indication for Sprycel (dasatinib) to include the treatment of children and adolescents aged 1 year to 18 years with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP), and to include a powder for oral suspension formulation. The approval follows a positive opinion issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use on April 26, 2018, and makes Sprycel the first ever tyrosine kinase inhibitor to be approved in a powder formulation for administration in pediatric patients and patients who cannot swallow tablets.

The EC approval is based on data from CA180-226 (NCT00777036), the largest prospective trial evaluating the safety and efficacy of Sprycel in pediatric patients newly diagnosed with CP-CML, and in those resistant to or intolerant of imatinib.

“Treatment options for pediatric patients with CML are limited, as are formulations that correspond with the unique demands of children with cancer,” said Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb. “Our decision to pursue an expanded indication for Sprycel in this new patient population and as a new formulation is indicative of our commitment to extending the potential of our medicines to address the unmet needs of patients with cancer, regardless of the incidence of the disease.”

https://bit.ly/2tWZWHh

Clovis OKd to file for new ovarian cancer indication for med in Europe

• The filing is based on positive phase 3 ARIEL3 clinical trial data in which rucaparib significantly improved progression free survival (PFS) compared to placebo in all primary efficacy ovarian cancer patient populations
• Timing of validation by EMA may allow for a CHMP opinion on maintenance treatment by year-end 2018

Clovis Oncology, Inc. (NASDAQ: CLVS) today announced that the European Medicines Agency (EMA) has validated the application for a Type II variation to the marketing authorization for Rubraca^® (rucaparib) to include maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum based chemotherapy. This validation confirms the submission is complete and begins the EMA’s centralized review process.

“We are very pleased to receive validation of the variation to the Rubraca marketing authorization by the EMA, which brings us a step forward in making rucaparib available to more women with recurrent ovarian cancer in Europe,” said Patrick J. Mahaffy, CEO and President of Clovis Oncology.

This submission is based on the positive results from the phase 3 ARIEL3 study, which evaluated rucaparib in the ovarian cancer maintenance treatment setting among three populations: 1) BRCA mutant (BRCAmut+) 2) HRD positive inclusive of BRCAmut+ and, 3) all patients treated in ARIEL3. ARIEL3 successfully achieved its primary endpoints, extending investigator assessed progression-free survival (PFS) versus placebo in all patients treated, regardless of BRCA status. Safety findings from the ARIEL3 trial were consistent with previous clinical trials.

In May 2018 rucaparib was granted Marketing Authorization in Europe for adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum based chemotherapy, and who are unable to tolerate further platinum based chemotherapy.¹

Based on the timing of this submission, the company anticipates an opinion from the Committee for Medicinal Products for Human Use (CHMP) by end of 2018.

https://bit.ly/2Nt0vkf

Boston Scientific to Acquire Cryterion Medical

Boston Scientific Corporation (NYSE: BSX) today announced a definitive agreement to acquire Cryterion Medical, Inc., a privately-held company developing a single-shot cryoablation platform for the treatment of atrial fibrillation (AF). The addition of this cryoballoon platform positions the company as the first to have both cryothermal and radiofrequency (RF) single-shot, balloon-based ablation therapies in its portfolio. Boston Scientific has been an investor in Cryterion since its inception in 2016 and the transaction price for the approximately 65 percent remaining stake not already owned by Boston Scientific consists of $202 million in up-front cash.

The quickly expanding global electrophysiology (EP) market is estimated to reach $5 billion in 2018. Additionally, single-shot ablation therapies are believed to be the fastest growing sub-segment within the EP market, with rates well into in the double digits, and trending toward more than $1 billion over the next few years.

Patients with AF – a common heart rhythm disorder – are often treated with anti-arrhythmic drugs as well as cardiac ablation. Ablation therapy is the process of delivering RF (heating) or cryothermal (cooling) energy to the areas of the heart muscle responsible for the abnormal heart rhythm. Both types of energy can be used to isolate pulmonary veins, which are often the source of AF.

The Cryterion Medical cryoablation platform uses cryothermal energy to interrupt the irregular electrical signals that can cause AF. Developed with a next-generation balloon catheter, advanced mapping catheter, steerable sheath and enhanced console, the system is designed to streamline overall procedural workflow, enhance maneuverability and improve positioning in challenging anatomy.

“Initial clinical study results demonstrate that our system has a promising safety profile as well as acute efficacy,” said Keegan Harper, president and chief executive officer, Cryterion Medical, Inc. “We look forward to bringing this advanced cryoablation system to market with the support of Boston Scientific.”

Performance of the cryoablation system from Cryterion Medical is being investigated in a clinical study in Europe. Clinical evidence from this study will be included in a regulatory submission for CE Mark, expected in early 2019. The company will also pursue regulatory approval in the U.S. and plans to submit an investigational device exemption (IDE) application to the U.S. Food and Drug Administration, with patient enrollment expected to begin in 2019.

“The acquisition of Cryterion Medical enhances our AF ablation procedure offerings, allowing physicians to select a therapeutic option based on clinical preference and specific patient needs,” said Kenneth Stein, M.D., senior vice president and chief medical officer, Rhythm Management and Global Health Policy, Boston Scientific. “We are committed to providing physicians with a comprehensive suite of therapies that lead the way for clinical advancements and address the needs of the increasing population of patients with AF.”

Boston Scientific expects the transaction to be immaterial on an adjusted earnings per share basis through 2020, and accretive thereafter. On a GAAP basis for 2019 and subsequent years, the transaction is expected to be less accretive, or more dilutive as the case may be, due to amortization expense and acquisition-related net charges. For 2018 on a GAAP basis, the transaction is expected to be accretive due to a one-time gain on prior investment.

https://bit.ly/2tXUgMV

Natera target upped by Piper

Natera price target raised to $21 from $18 at Piper Jaffray. Piper Jaffray analyst William Quirk raised his price target for Natera to $21 after Dr. Sarwal presented on the company’s dd-cfDNA test for monitoring kidney health at the TTS meeting in Madrid. Dr. Sarwal reiterated the data released last week and noted that Natera’s assay can be used logituditally, like AlloSure, which is expected, Quirk tells investors in a research note. Disappointingly, Dr. Sarwal was not certain what the AUC for creatinine was in the broader cohort, the analyst adds. He continues to believe Natera has “material opportunity” in transplant, but that CareDx (CDNA) has a “significant head start in a concentrated market.” Quirk keeps an Overweight rating on Natera.

https://bit.ly/2KwK1JX