Mallinckrodt, NPXe Fast Tracked For Phase 3 Trial Of Inhaled Xenon Therapy

— Drug to be studied for improved functional outcomes and survival rates for patients resuscitated after a cardiac arrest —   

Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, and NPXe Limited (“NeuroproteXeon” or “NPXe”) today announced that the United States Food and Drug Administration (FDA) recently granted Fast Track designation to NPXe’s Phase 3 trial of xenon gas for inhalation in Post Cardiac Arrest Patients. Fast Track designations are provided to drug candidates that “treat a serious condition and fill an unmet medical need.” Xenon gas for inhalation is an investigational drug, the safety and effectiveness of which have not yet been established.

The key benefits to recipients of a Fast Track designation include more frequent contact with the FDA on the development program and the option of Rolling Review, which allows a company to submit completed sections of the New Drug Application (NDA) for individual review by the Agency. This compares with the normal process where the entire NDA must be completed before submission. The frequency of communication under the Rolling Review better assures that questions and issues are resolved quickly, potentially leading to earlier drug approval and patient access.

Bill Burns, NPXe’s Chief Executive Officer, commented, “Receiving Fast Track designation expedites the review process and, if approved, inhaled xenon gas will help treat patients with an unmet medical need. It further demonstrates we are taking the appropriate steps to rapidly bring this important treatment to the market.”

“We are pleased to see the FDA recognize the potential value xenon gas for inhalation can provide in addressing these underserved patients who have a critical need,” said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. “We look forward to the upcoming start of the Phase 3 trial and learning more about this potential therapeutic option in a population of resuscitated cardiac arrest patients.”

The companies anticipate the trial will commence in the coming months, with the first patients enrolled in the U.S.

About Xenon Gas for Inhalation in Post-Cardiac Arrest Syndrome (”PCAS”)
Xenon is a noble gas that has been used as an inhaled therapy in several studies to date. In PCAS, more N-methyl-D-aspartate receptors (“NMDAR”, a calcium channel found in neurones) are activated, causing extreme ion imbalances, neuronal damage and cell death. Studies have shown that xenon may help to inhibit the NMDAR through a unique inhibition at the glycine-binding site and can help moderate the flow of damaging ions through the calcium channel. By mitigating neuronal damage and cell death, xenon may be able to improve functional outcomes and reduce mortality rates in survivors. The FDA has not yet established the safety and effectiveness of xenon gas for inhalation for PCAS.

https://bit.ly/2LmPI8P

Kala Gets FDA OK for Ocular Post-Op Inflammation and Pain Med

– First Twice-Daily Ocular Corticosteroid Indicated for the Treatment of Post-Operative Inflammation and Pain Following Ocular Surgery –

– Kala to Host Conference Call Today at 5:00pm (ET) –

Kala Pharmaceuticals, Inc. (NASDAQ:KALA), a biopharmaceutical company focused on the development and commercialization of therapeutics using its proprietary mucus-penetrating particle (MPP) technology, today announced that the U.S. Food and Drug Administration (FDA)has approved INVELTYS^TM (loteprednol etabonate ophthalmic suspension) 1% for the treatment of post-operative inflammation and pain following ocular surgery. INVELTYS is the first twice-daily (BID) ocular corticosteroid approved for this indication.

“The FDA approval of INVELTYS is a tremendous milestone for Kala,” said Kim Brazzell, Ph.D., Chief Medical Officer of Kala Pharmaceuticals. “Approximately 8 million patients undergo ocular surgeries each year. The approval of INVELTYS offers patients and their eye care professionals the first and only BID ocular corticosteroid therapy that has been shown in clinical trials to be clinically effective while maintaining a proven safety profile, which may improve compliance and prove less burdensome for patients. We believe INVELTYS will be an important addition to eye care professionals’ treatment armamentarium.”

All other ocular steroids are only approved for four-times-a-day dosing. This more frequent dosing requirement can lead to issues for both doctors and patients. Corticosteroids are the foundation of therapy for post-ocular surgery care, with the key goal of controlling inflammation and pain which is caused by surgical trauma to the eye. The use of ocular steroids post-surgery is to achieve a rapid reduction of inflammation and to promote healing of the eye. Therefore, ensuring close adherence to the steroid regimen is a critical factor for physicians in the post-surgery care of the patient and eventual overall success of the procedure.

“Today’s approval of INVELTYS is welcome news for the eye care community as it provides a clear advancement in the treatment for inflammation and pain following ocular surgery. Having access to a BID corticosteroid in a novel nanoparticle formulation with proven safety and efficacy will make a positive impact on the management of my post-operative patients,” said Terry Kim, M.D., Professor of Ophthalmology and Chief, Cornea and External Disease Division, Duke University Eye Center.

https://bit.ly/2PvPEH0

Innovate Biopharmaceuticals Teams Up With CRO for Phase III Celiac Trial

Shares of Innovate Biopharmaceuticals are up more than 7 percent in premarket trading after the company announced it signed an agreement with privately-held Amarex Clinical Research to provide data management and biostatistics for its planned Phase III celiac disease trial.

Amarex, Innovate announced this morning, will provide the company with electronic data capture solutions and associated services for data management and biostatistics.

June Almenoff, chief medical and chief operating officer of North Carolina-based Innovate, said Amarex has a strong reputation for its expertise in biostatistics and data management.

“I am pleased to be working with Amarex to support our Phase III trial. Our clinical team has been impressed with Amarex’s capabilities, and we look forward to a productive working relationship,” Almenoff said in a statement.

Innovate is investigating larazotide acetate as a treatment for celiac disease. The company said larazotide is the “only drug which has successfully met its primary endpoint with statistical significance” in a Phase IIb trial. For celiac patients, larazotide acetate “renormalizes the dysfunctional intestinal barrier” through a mechanism that decreases intestinal permeability, which is sometimes referred to as “leaky gut.” It also reduces antigen trafficking, such as gliadin fragments in celiac disease, according to data provided by Innovate. Larazotide acetate could also potentially prove to be a treatment for other disorders, including NASH (nonalcoholic steatohepatitis), Crohn’s disease, ulcerative colitis, irritable bowel syndrome, type 1 diabetes mellitus chronic kidney disease.

Celiac disease is an autoimmune disorder that causes about one in 100 people to have a negative reaction to the ingestion of gluten. When gluten is eaten by people with celiac disease, their body’s immune system responds with an attack on the small intestine.

Earlier this summer, Innovate presented data at the Digestive Disease Week conference that showed larazotide acetate “stimulates recovery of ischemic-injured intestine in a dose-dependent manner associated with restoration of tight junctions.”

That trial concluded at the end of 2017 and Innovate has been meeting with the U.S. Food and Drug Administration about its Phase III trial. That late-stage trial will begin later in 2018, the company said. Larazotide has received Fast Track designation from the FDA for celiac disease.

“We are excited to support Innovate in the development of its novel therapeutic, which has the potential to help so many patients suffering from celiac disease. We look forward to working closely with Innovate’s experienced team to advance the clinical development of larazotide for this underserved population,” Kazem Kazempour, president and chief executive officer of Amarex said in a statement.

https://bit.ly/2PB82yz

FDA Launches New Draft Guidance for Osteoarthritis Treatments

The U.S. Food and Drug Administration (FDA) has posted new draft guidance that will guide drug and medical device manufacturers that aim to develop treatments for “the underlying pathophysiology and structural progression” of osteoarthritis (OA).

In its short draft guidance, which was first reported by Regulatory Affairs Professional Society(RAPS), the FDA said that to date, approvals for treatments of osteoarthritis have been “based on patient-reported outcome measures that assess pain and function.” However, the FDA said that treatments that aimed at the underlying pathophysiology and structural progression of the disease have so far been elusive and constitute an unmet medical need. The guidance will not address the improvement of OA symptoms such as pain or functional impairment. The FDA said those are important outcomes and will be addressed in a future guidance.

The new draft guidance was issued days after Regeneron and Teva posted positive Phase IIIresults for fasinumab as a treatment for osteoarthritis (OA) of the knee or hip. At 16 weeks patients experienced significantly less pain and also showed significantly improved functional ability from baseline.

As the draft guidance moves forward, the FDA noted that device makers and drug manufacturers should consider several structural endpoints issues to include in a finalized document. The FDA said makers should be aware of the multifactorial and complex etiopathogenesis of the disease. Additionally, they should note the “well-recognized discordance between structural changes and signs/symptoms/function.” Also, the lack of standard definitions of disease progression, as well as the absence of endpoints to reliably assess the ability of a product to alter OA disease progression should all be noted.

“Because of the complex and variable pathologic changes through which OA impairs function and leads to long-term disability and/or joint replacement, at this time it is unclear what magnitude of change in structural endpoints would translate to a clinically meaningful benefit to patients,” the FDA said in the draft guidance.

Because of that, no structural endpoints have been used for traditional or accelerated approval in OA to date, the FDA added.

In order to accept structural endpoints for OA, the FDA said there should be “substantial confidence” based on clinical evidence or a comprehensive understanding of the disease process and mechanism of action where such an endpoint will “reliably predict an effect on the clinical outcomes of interest.”

“The ultimate goal of treatments related to inhibition of structural damage or targeting the underlying pathophysiology associated with OA is to avoid or significantly delay the complications of joint failure and the need for joint replacement, and also to reduce the deterioration of function and worsening of pain,” the FDA said.

As the FDA pushes forward on new OA guidance, it asked for input from drug and device manufacturers to address the considerations.

https://bit.ly/2o47YKR

AstraZeneca COPD Drug Fails to Surpass Rival Glaxo Treatment

AstraZeneca has seen another setback in a late-stage trial for chronic obstructive pulmonary disease (COPD) treatments. The latest stumbling block includes a failure for AstraZeneca’s investigational treatment to distinguish itself from a drug already marketed by rival GlaxoSmithKline.

Today AstraZeneca said its Phase IIIb drug Bevespi Aerosphere (glycopyrronium/formoterol fumarate) did not do worse than GSK’s Anoro Ellipta, (umeclidinium/vilanterol) on peak forced expiratory volume in one second (FEV1). However, the drug did not do better than the GSK inhaler. Additionally, AstraZeneca said its inhaler displayed non-inferiority on trough FEV1.

Bevespi Aerosphere, a fixed-dose dual bronchodilator combining glycopyrronium, a long-acting muscarinic agonist (LAMA), and formoterol fumarate, a long-acting beta2-agonist (LABA), was approved by the U.S. Food and Drug Administration (FDA) in 2016 for the long-term maintenance treatment of airflow obstruction in COPD. The drug is under review by the European Medicines Agency (EMA). AstraZeneca said it expects a regulatory ruling later this year.

Colin Reisner, head of AstraZeneca’s respiratory development division, noted that the safety and efficacy of Bevespi Aerosphere have already been established in previous trials that involved more than 5,000 patients. Reisner said the performance of Bevespi Aerosphere in the AERISTO trial is inconsistent with previous data the company has collected through other trials.

“A full analysis is underway to understand and characterize these findings and will be presented at a forthcoming medical meeting,” Reisner said in a statement.

This is the second stumble for AstraZeneca’s COPD treatments. In May, the company reported its add-on asthma treatment Fasenra failed to hit endpoints in a Phase III trial of patients with moderate to very severe COPD. Fasenra’s failure to achieve a statistically significant reduction of exacerbations in the TERRANOVA trial came hard on the heels of its failure in the Phase III GALATHEA trial. In that trial, Fasenra also failed to achieve a statistically-significant decrease of exacerbations in COPD patients.

COPD is a progressive disease which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. It affects an estimated 384 million people worldwide and is predicted to be the third-leading cause of death by 2020. About 30 to 40 percent of moderate to severe COPD patients on triple inhaled therapy remain uncontrolled and continue to experience exacerbations.

While the two aforementioned medications hit roadblocks in COPD development, in January AstraZeneca noted its three-in-one inhaler PT010 improved lung function in COPD patients. The trial compared PT010 to Bevespi Aerosphere, Symbicort Turbuhaler and PT009. The company said PT010 outperformed the other drugs, in a statistically significant manner.

AstraZeneca is trying to remain close to GSK in hopes of putting up a medication that can outperform GSK’s Trelegy Ellipta, which was approved for use in the United States in September 2017. The drug is a once-daily inhalation a combination of an inhaled corticosteroid (ICS), a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-adrenergic agonist (LABA).GSK co-developed Trelegy Ellipta with Innovia, Inc. If AstraZeneca’s drug is approved, some analysts suggested the GSK drug will be preferred due to it being a once-daily dose instead of twice-daily.

A focus on respiratory drugs has been key to AstraZeneca’s strategy, particularly since the $575 million acquisition of Takeda Pharmaceutical’s core respiratory business, including global rights to roflumilast, a treatment for COPD.

https://bit.ly/2P1Djcx

Allergan price target raised to $202 from $181 at Morgan Stanley

Allergan price target raised to $202 from $181 at Morgan Stanley. Morgan Stanley analyst David maintained an Overweight rating on Allergan and raised his price target to $202 from $181. In a research note to investors, Risinger says the company’s upcoming Aesthetics Investor Day on September 14 should help investors “appreciate” the durability of the franchise. Additionally, the analyst experts ubrogepant for acute migraine safety data will be “supportive” of approval in 2H, with an FDA filing in early 2019 and launch in early 2020, and says there is “upside” beyond his base case if rapastinel for severe depression Phase 3 data is compelling in 1H19. Risinger believes the pipeline newsflow on migraine and depression could potentially benefit Allergan’s stock multiple.

https://bit.ly/2MO5LBs

Biohaven Pharmaceutical transferred with an Overweight at Cantor Fitzgerald

Cantor Fitzgerald analyst Charles Duncan took over coverage of Biohaven Pharmaceutical with an Overweight rating and $55 price target. The analyst sees Biohaven’s rimegepant in acute migraine as the key driver of shareholder value.

https://bit.ly/2w7q6YR