Ocular Therapeutix Submits sNDA for Treatment of Ocular Inflammation

Ocular Therapeutix™, Inc. (NASDAQ: OCUL), a biopharmaceutical company focused on the formulation, development, and commercialization of innovative therapies for diseases and conditions of the eye, today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for DEXTENZA (dexamethasone ophthalmic insert). The sNDA filing seeks to expand the current indication for DEXTENZA to include the treatment of ocular inflammation following ophthalmic surgery. The Company expects that the FDA review will be completed in the second half of 2019.

DEXTENZA is the first FDA-approved intracanalicular insert delivering dexamethasone to treat post-surgical ocular pain for up to 30 days with a single administration. DEXTENZA received FDA approval in November 2018 for the treatment of ocular pain following ophthalmic surgery. DEXTENZA is a resorbable, preservative-free ophthalmic insert that is placed in the lower lacrimal punctum and into the canaliculus of the eye.

“Submission of this sNDA on the heels of the initial DEXTENZA approval is another significant milestone for Ocular Therapeutix. The potential market opportunity for postoperative ocular pain and inflammation is substantial and there remains an important unmet need to address the issue of non-compliance given currently available treatment options,” said Antony Mattessich, the Company’s President and Chief Executive Officer. “This is another major step toward our goal of making eye-drop therapies obsolete.”

The sNDA is supported by the two previous Phase 3 clinical trials and safety and efficacy data from an additional prospective, multicenter, randomized, controlled Phase 3 clinical trial of DEXTENZA (n=438) in cataract surgery patients that demonstrated statistical significance compared to the vehicle control for the endpoints of absence of ocular pain (p<0.0001) and absence of inflammation (p<0.0001). The ocular safety profile was similar to that demonstrated in the two prior Phase 3 clinical trials. Data from the third Phase 3 clinical trial were recently published in the Journal of Cataract & Refractive Surgery (JCRS) in October 2018.

https://www.streetinsider.com/Corporate+News/Ocular+Therapeutix+%28OCUL%29+Submits+sNDA+for+DEXTENZA+for+Treatment+of+Ocular+Inflammation+Following+Ophthalmic+Surgery/14996742.html

Intercept Pharma (ICPT) Receives a Buy from B.Riley FBR

In a report issued on January 7, Mayank Mamtani from B.Riley FBR reiterated a Buy rating on Intercept Pharma (ICPT). The company’s shares closed yesterday at $110.82.

Mamtani noted:

“Earlier today (1/7/2019), Intercept Pharmaceuticals, Inc. (ICPT) announced two key updates to the two Phase III trials ongoing for its lead candidate, obeticholic acid (OCA), or Ocaliva, in patients afflicted with non-alcoholic steatohepatitis (NASH); (i) Phase III REGENERATE trial in F2-F3 NASH patients to report 72-week interim analysis data in 1Q, narrowing prior guidance of 1H19; and (ii) Phase III REVERSE trial in F4 NASH patients with compensated cirrhosis has now completed enrollment. In parallel, ICPT has also acquired U.S. rights to bezafibrate from Aralez Pharmaceuticals as an effort to pioneer the next phase of innovation for primary biliary cholangitis (PBC) patients after Ocaliva was originally approved by FDA in 2019. Financials of the deal were undisclosed.”

https://www.smarteranalyst.com/brief/intercept-pharma-icpt-receives-a-buy-from-b-riley-fbr/

As Western Fears Mount, China Silences Promotion of Thousand Talents Plan

The government of China is reportedly asking officials to quiet down promotion of a programaimed at recruiting western scientists to work in that country.

In 2010, China launched the “Thousand Talents Plan,” which is aimed at attracting top researchers from across the globe. The program targets individuals under the age of 55 who are willing to work in China full-time. Those selected for the program are given full professorships or the equivalent in universities and research institutes. The “Thousand Talents Plan” was created with an aim to “gather global wisdom,” according to the plan’s website. However, the government is now looking to tamp down talk of the program following increased concerns in the United States, the Financial Times reported.

According to the report, law enforcement leaders in the U.S. have characterized China’s plan as a program aimed more at the theft of intellectual property than an attempt to bolster its own scientific research programs. The Financial Times reported that at the end of 2018, Bill Priestap, assistant director of the counter-intelligence division of the Federal Bureau of Investigation, told a U.S. Senate committee that the Thousand Talents Plan encourages “theft of intellectual property from US institutions.” That warning came after Texas Tech University warned members of its faculty that the Thousand Talents Plan was part of a “broader strategy to build technological superiority.” The warning also claimed that the U.S. Department of State and members of Congress saw the western recruitment program as being “closely allied to the Chinese military,” the Financial Times reported. In addition, the Financial Times said the Texas Tech warning said that those western scientists who received awards from the Chinese program could be barred from securing U.S. government grants in the future.

When BioSpace initially wrote about the Thousand Talents Plan in November 2018, data showed that a very small percentage of U.S. researchers and scientists had taken advantage of the Chinese program. That number is likely to remain small due to the obstacles that the U.S. government is placing  before those researchers who may want to come back home to work. It’s for that reason, the Financial Times said, that the Chinese government is tamping down publicity surrounding the Thousand Talents Plan.

As of this month, the Chinese Thousand Talents Plan has recruited approximately 6,000 scientists and researchers from the west. Those who take the offer typically receive about $146,670 in what the Financial Times called “a personal ‘setting-up’ grant,” as well as an additional grant amount.

While the U.S. government may be suspicious of the recruiting of U.S.-based scientists, that has not prevented U.S. and other western pharma companies from forging relationships with many Chinese partners as they seek to open the booming Chinese biopharma market to more western-developed drugs, particularly oncology medications. Over the next several years, China is expected to see exponential growth in its pharmaceuticals market. Growth projections show China’s pharmaceutical market is expected to grow to between $145 billion and $175 billion by 2022. Since 2012, there has been explosive growth in cooperation between Chinese companies and the west in research and development.

https://www.biospace.com/article/as-western-fears-mount-chinese-government-silences-promotion-of-thousand-talents-plan/

Conn. Judge Dismisses Lawsuits v. Purdue Pharma, Other Opioid Drugmakers

Opioid drugmakers being sued in the state of Connecticut are breathing a big sigh of relief today after a judge dismissed lawsuits filed by 37 different municipal governments.

In the Hartford Superior Court, Judge Thomas Moukawsher ruled that the lawsuits brought by the government entities against drug manufacturers such as Purdue Pharma were not allowable. Moukawsher said those lawsuits were not “government enforcement actions” such as those that are filed under consumer protection and public health laws, The Associated Pressreported. The judge said that the cases, which are seeking financial reparations from the companies to offset costs the governments have spent fighting addiction, were filed as “ordinary civil cases.” Moukawsher said the lawsuits cannot continue unless proof is shown that the companies being sued “directly caused them the financial losses they seek to recoup.”

This puts the cities in the same position in claiming money as the brothers, sisters, friends, neighbors, and co-workers of addicts who say they have also indirectly suffered losses by the opioid crisis. That is to say — under long-established law — they have no claims at all,” Moukawsher wrote in his opinion, according to the AP.

As could be expected, the governments and their legal teams are planning to appeal the decisions, while the companies are agreeing with Moukawsher’s ruling. Purdue Pharma, the maker of OxyContin, the drug most often cited in abuse lawsuits, called the ruling the right decision. Purdue said that it agreed with the conclusion that “opioid manufacturers cannot be legally responsible to cities for the indirect harms they claim they experienced as a result of the opioid crisis,”

“We share these communities’ concerns about the opioid crisis, and we remain committed to working collaboratively, bringing meaningful solutions forward to help address this public health challenge,” Purdue said in its statement, the AP noted.

For now, though, Moukawsher’s ruling is something of a first of its kind. In Ohio, a state that is being watched as a benchmark case for the lawsuits brought against opioid manufacturers and distributors, a judge refused to dismiss more than 1,400 cases last month, the AP noted.

Last year BioSpace highlighted a number of the lawsuits that have been filed against the opioid-makers. The arguments cited in the lawsuits typically say that the companies, such as Purdue, engaged in deceptive marketing practices that contributed to high addiction rates. Also, the lawsuits argue that the companies downplayed concerns over abuse, as well as allegations of complicity in the large amounts of opioids delivered to small-town pharmacies.

According to the U.S. Department of Health and Human Services, 116 Americans die daily from opioid overdoses.

https://www.biospace.com/article/connecticut-judge-dismisses-lawsuits-brought-against-purdue-pharma-other-opioid-drugmakers/

Ono/Bristol Opdivo improves survival in esophageal cancer

Nivolumab (Opdivo) demonstrated a significant extension in overall survival (OS) versus chemotherapy in patients with unresectable advanced or recurrent esophageal cancer that is refractory to or intolerant of fluoropyrimidine plus platinum-based therapy, according to topline findings of the phase III ATTRACTION-3 study (ONO-4538-24/CA209-473).¹

This is the first checkpoint inhibitor to show a statistically significant extension in OS for patients with PD-L1–unselected, unresectable advanced or recurrent esophageal cancer, announced Ono Pharmaceutical and Bristol-Myers Squibb (BMS), who collaborated on ATTRACTION-3 with the PD-1 inhibitor. Results of the study will be presented at an upcoming medical meeting.

In the international, multicenter, open-label, randomized ATTRACTION-3 trial, approximately 390 patients with esophageal cancer who were refractory to or intolerant of 1 prior combination therapy with fluoropyrimidine and platinum-based treatment received either nivolumab at 240 mg/body solution intravenously (IV) every 2 weeks or chemotherapy with docetaxel or paclitaxel until disease progression or severe adverse events (AEs). Docetaxel was administered at 75 mg/m2 IV every 2 weeks and paclitaxel at 100 mg/m² weekly for 6 weeks followed by a 2-week treatment holiday.

The primary endpoint was OS; secondary endpoints were progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety.

To be eligible for enrollment, patients must have been ≥20 years of age, be refractory to or intolerant of standard therapy, have an ECOG performance score of 0 or 1, and a life expectancy of at least 3 months. Those with a current or past history of severe hypersensitivity to any other antibody products, multiple primary cancers, with symptomatic brain or meninx metastases, and active or suspected autoimmune disease were excluded.

Two-year findings from the open-label phase II ATTRACTION-01/ONO-4538-07 trial were presented at the 2017 ESMO Congress.² In the trial, 65 patients with esophageal squamous cell carcinoma received nivolumab at 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. The primary endpoint was ORR evaluated by an independent review committee; secondary endpoints were OS, safety, PFS, and DOR.

Preliminary results showed that the ORR was 17.2% (95% CI, 9.9%-28.2%) as of May 17, 2015. With the 2-year update, the ORR was 17.2% and the median DOR was 11.7 months. Kaplan-Meier estimates for 1-, 1.5-, and 2-year OS rates were 45.3%, 25.0%, and 17.2%, respectively. One-, 1.5, and 2-year PFS rates were 10.3%, 8.6%, and 8.6%, respectively.

Regarding safety, grade 3/4 AEs were reported in 29.2% of patients (n = 19). The most common AEs were diarrhea (21.5%), decreased appetite (18.5%), lung infection (13.8%), and cough (12.3%). A total 7 patients discontinued nivolumab due to treatment-related AEs, and no treatment-related deaths were reported.

Approximately 570,000 new cases are diagnosed with esophageal cancer worldwide annually and approximately 510,000 deaths from this disease per year. There are currently no effective second-line treatments for patients who progress on cisplatin and 5-fluorouracil, Ono Pharmaceutical stated in a press release.

In addition, Ono Pharmaceutical is conducting a clinical development program that includes esophageal cancer, gastroesophageal junction cancer, small cell lung cancer, hepatocellular carcinoma, glioblastoma, urothelial cancer, ovarian cancer, and biliary tract cancer.

A collaboration agreement began in 2011 when Ono Pharmaceutical granted BMS territorial rights to develop and commercialize nivolumab worldwide except in Japan, South Korea and Taiwan, which is where ONO retained all rights to nivolumab except the United States at the time. In July 2014, Ono and BMS expanded the collaboration agreement to jointly develop and commercialize multiple immunotherapies alone and in combination for patients with cancer in Japan, South Korea and Taiwan.

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References

1. Opdivo® (Nivolumab) Demonstrates a Significant Extension in Overall Survival Versus Chemotherapy in Patients with Unresectable Advanced or Recurrent Esophageal Cancer in Phase III Clinical Study. ONO Pharmaceutical Co., LTD. Published January 10, 2019. https://bit.ly/2D2P3bX?rel=0&#8243; . Accessed January 10, 2019.
2. Kitagawa Y, Doki Y, Kato K, et al. Two year survival and safety update for esophageal squamous cell carcinoma treated with nivolumab (ATTRACTION-01/ONO-4538-07). Ann Oncol. 2017;28(5):mdx369.022. doi: 10.1093/annonc/mdx369.022.

https://www.onclive.com/web-exclusives/nivolumab-improves-os-in-advanced-or-recurrent-esophageal-cancer

New drug screen uncovers small-molecule immuno-oncology candidates

Checkpoint inhibitors to treat cancer, such as Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo, are antibodies: bulky proteins that have to be given intravenously. Those drugs are effective at removing barriers that normally prevent the immune system from recognizing and attacking cancer. But they’re inconvenient for patients, and not everyone responds well to them.

Scientists at Emory University wanted to search for small molecules—chemicals that can easily be packed into pills—that might have similar or even better immune-boosting effects. So they created a screening test that uses human immune cells to rapidly sort through vast libraries of chemicals and pinpoint the substances that can prompt the immune system to suppress cancer growth.

The system, dubbed HTiP, turned up an emerging class of drugs called IAP antagonists, which are already in studies to treat cancer. The screen confirmed that the drugs enhance the immune response to cancer, they reported in the journal Cell Chemical Biology. And they believe the test will be able to be expanded so it can uncover molecules that work in many different ways to activate an anticancer immune response.

HTiP, which stands for “High-Throughput Immunomodulator Phenotypic Screening Platform,” uses a mix of immune cells and cancer cells that carry a particular mutation in the KRAS gene. The mutation suppresses the immune system’s ability to fight the disease.

The Emory team screened 2,000 compounds using HTiP, searching for drug candidates that could reverse the effect of the KRAS mutation. They isolated the drug birinapant, an IAP antagonist that is currently being developed by Medivir, which is collaborating with Merck on a human trial of birinapant combined with Keytruda in patients with a variety of solid tumor types.

The fact that HTiP pulled up IAP antagonists—and birinapant in particular—”was strong evidence for their relevance as immune enhancers,” said lead author Haian Fu, Ph.D., chair of the department of pharmacology and chemical biology at Emory University School of Medicine, in a statement. “It was a timely validation of our system.”

Birinapant has encountered some bumps along the development path. It was originally developed by TetraLogic to treat hepatitis B, but safety concerns forced the company to halt an early trial and pull the plug on a planned initial public offering. Birinapant failed trials in myelodysplastic syndrome. Medavir bought the drug from TetraLogic in 2016.

Medivir and Merck are enrolling 135 cancer patients in their phase 1/2 combo trial, which they expect to complete in 2021.

Emory’s Fu says HTiP can use many types of immune cells to screen for immune-boosting compounds. And it can detect immune reactions that are either adaptive or innate. He adds that the system could be modified to test the effects of small-molecule drugs on other cancer-causing mutations.

The next step for Fu’s team is to expand HTiP so it can cover other mutations and screen many more compounds beyond the initial 2,000 they examined. “There are many targets inside the cell,” he said. “We want to shine a light on those intracellular targets.”

https://www.fiercebiotech.com/research/new-drug-screen-uncovers-small-molecule-candidates-for-immuno-oncology

Acadia jumps after higlighting Nuplazid opportunity in PDP treatment

Acadia jumps after higlighting Nuplazid opportunity in PDP treatment  Shares of Acadia (ACAD), a company focused on central nervous system disorders, are rising after its presentation at the JP Morgan Healthcare Conference Wednesday night. SIGNIFICANT COMMERCIAL OPPORTUNITY FOR NUPLAZID: Nuplazid is a selective serotonin inverse agonist/antagonist, or SSIA, used to treat Parkinson’s disease psychosis. During the JP Morgan conference, Acadia said it anticipated 2018 Nuplazid revenue of $220M-$225M, with Q3 Nuplazid revenue of $58.3M, representing 64% growth year-over-year. With the company’s launch of a 34 milligram capsule of Nuplazid in Q3, Acadia CEO Steve Davis said: “We think with the new drug approved and as patients get more and more experience with a very favorable tolerability profile and the strong efficacy that we have that we’ll be able to grow that market and physicians will likely begin treating earlier in the treatment paradigm.” PRICE ACTION: Shares of Acadia are up approximately 5.8% to $20.89 in afternoon trading.

https://thefly.com/landingPageNews.php?id=2847137