Alexion Positive Top Line in Phase 3 Hemolytic Uremic Syndrome Study

Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) today announced that the Phase 3 study of ULTOMIRIS (ravulizumab-cwvz), the company’s long-acting C5 complement inhibitor, met its primary objective in complement inhibitor-naive patients with atypical hemolytic uremic syndrome (aHUS).

In the initial 26 week treatment period, 53.6 percent of patients (95% CI [39.6%, 67.5%]) demonstrated complete thrombotic microangiopathy (TMA) response. ULTOMIRIS provided immediate and complete inhibition of the complement C5 protein that was sustained over the entire eight-week dosing interval.

The primary endpoint of complete TMA response was defined by hematologic normalization and improved kidney function. Treatment with ULTOMIRIS resulted in: reduced thrombocytopenia, as measured by normalization in platelet count, in 83.9 percent of patients (95% CI [73.4%, 94.4%]), reduced hemolysis (the destruction of red blood cells), as measured by normalization in lactate dehydrogenase (LDH) level, in 76.8 percent of patients (95% CI [64.8%, 88.7%]) and improved kidney function, as measured by 25 percent improvement in serum creatinine level from baseline, in 58.9 percent of patients (95% CI [45.2%, 72.7%]). For patients on dialysis at enrollment, baseline was established after they had come off dialysis.

https://www.marketscreener.com/ALEXION-PHARMACEUTICALS-8334/news/Alexion-Pharmaceuticals-Announces-Positive-Top-Line-Results-from-Phase-3-Study-of-ULTOMIRIS-in-Com-27932550/

Cipla receives final approval for generic version of Pfizer’s Depo-Provera

Cipla Limited (BSE: 500087; NSE: CIPLA EQ and hereafter referred to as ‘Cipla’) today announced that it has received final approval for its Abbreviated New Drug Application (ANDA) for Medroxyprogesterone Injectable, 150mg/mL from the United States Food and Drug Administration (US FDA).

Cipla’s Medroxyprogesterone Injectable, 150mg/mL is AB-rated generic therapeutic equivalent version of Pfizer’s Depo-Provera. It is a progestin indicated only for the prevention of pregnancy. According to IQVIA (IMS Health), Depo-Provera and its generic equivalents had US sales of approximately $159M for the 12-month period ending November 2018.

https://www.marketscreener.com/CIPLA-9058821/news/Cipla-receives-final-approval-for-generic-version-of-Pfizer-s-Depo-Provera-27932566/

Trevena Sees Path Forward for Rejected Opioid Pain Medicine

Shares of Trevena soared nearly 120 percent in Monday trading after the company announced it has found a path forward for its intravenous opioid-pain reliever oliceridine.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter to the company in November, one month after an advisory committee rejected the drug. When the FDA issued the CRL, the regulatory agency requested additional clinical data on QT prolongation and indicated that the submitted safety database is not of adequate size for the proposed dosing. The FDA also requested certain additional nonclinical data and validation reports, Trevena said in November.

However, on Monday, Pennsylvania-based Trevena said that following a Type A meeting with the FDA, the agency provided hope for a path forward. On Monday, Trevena said it will submit a detailed protocol and analysis plan to the FDA soon and, following feedback, will initiate the required study in the first half of 2019. The FDA agreed that the company’s current safety database will support labeling at a maximum daily dose of 27 mg. Trevena also noted that the FDA requested that the company conduct a study in healthy volunteers to collect the requested QT interval data. The study should include placebo- and positive-control arms, the FDA said. Additional efficacy data was not required. The FDA did request supporting nonclinical data related to the characterization of the 9662 metabolite and the remaining product validation reports when the oliceridine NDA is resubmitted, the company said.

Carrie L. Bourdow, president and chief executive officer of Trevena, said the company is encouraged by the meeting results from the FDA and believes this is a path forward for regulatory approval.

“We remain committed to our mission of ensuring access to safe and effective treatment options for hospital patients who require an IV opioid to manage their moderate to severe acute pain,” Bourdow said in a statement.

Trevena has had issues getting oliceridine across the finish line. Not only did the FDA reject it in 2018, but the company also had issues with the drug following a late-stage analysis in 2017. Following a Phase III study, analysts questioned whether or not the drug could distinguish itself from morphine, particularly in some measures of safety. That resulted in a shakeup at the company that saw about 30 percent of the staff laid off in order to provide funds to support the continued development of the opioid treatment.

While the company does have a path forward to potentially see approval of oliceridine, Trevena is the subject of a class action lawsuit. The lawsuit was filed by investor-rights law firm Bernstein Liebhard in October after the FDA advisory committee rejected oliceridine. According to the lawsuit, Trevena executives, led by recently retired Trevena CEO Maxine Gowen, misled shareholders regarding an April 2016 end-of-phase meeting with the FDA. The lawsuit suggests that the company painted a rosy picture regarding the meeting with the FDA as the company planned to take oliceridine into Phase III trials.

https://www.biospace.com/article/trevena-sees-path-forward-for-rejected-opioid-pain-medicine/

Gates Foundation, Gilead, Others Drop $55M on Series B for Lyndra Therapeutics

Lyndra Therapeutics, based in Watertown, Mass., announced the closing of a Series B financing round worth $55 million. All original investors from the $23 million Series A round led by Polaris Partners were involved. New investors include HOPU Investments, Gilead Sciences, Invus, the Bill & Melinda Gates Foundation and Orient Life.

The funds raised will be used to advance the company’s lead product into Phase II clinical trials, expand its Phase I pipeline, and scale-up its manufacturing capacity. It expects to submit an Investigational New Drug Application (IND) for a long-acting pill for schizophrenia this year with plans to start a Phase II trial in 2020.

Lyndra focuses on reformulating drugs that are used daily into once-a-week or even monthly dosages. Extended-release drugs currently on the market generally deliver drugs for 12 to 24 hours. Lyndra’s technology allows for the slow release of active ingredients over time. The pills are about the size of a fish-oil capsule. Their size and shape slows digestion to about a week, where they then break into smaller pieces and pass through the gastrointestinal tract. They are also working on formulations that last longer.

Within the digestible pill is a star-shaped structure with six arms folded in on itself. As stomach acid dissolves the pill, the arms unfold, releasing the active ingredients over time. As the star unfolds it also becomes larger, so it stays in the stomach longer. In time, the arms break off and the rest of the pill passed through the GI tract.

“From the beginning, the patient experience is at the heart of what we’re trying to do at Lyndra,” Amy Schulman, Lyndra’s chief executive officer, told the Boston Business Journal. “If you try too hard to change people, you’ll knock your head against the wall. We’re changing the pill to fit how people behave, instead of trying to change people.”

The company’s pipeline for once-weekly dosing includes drugs for Alzheimer’s disease, psychiatric disorders, opioid use disorder, cardiovascular and metabolic diseases, immunology, HIV ART and PrEP. Its once-biweekly pipeline focuses on malaria vector control. And its once-monthly doing pipeline is an oral contraceptive. The most advanced is for Alzheimer’s and psychiatric diseases.

The company’s technology was developed in the laboratory of Robert Langer with the Massachusetts Institute of Technology (MIT). Langer and Schulman co-founded Lyndra. Schulman was a former attorney for the pharma industry and a partner recruited to run the LS Polaris Innovation fund created by Polaris Partners in 2014.

The Gates Foundation largely focuses on improving the health and wellbeing in individuals in developing countries. Lyndra’s focus on malaria drugs and the overall approach to sustained-release drugs makes total sense. And Gilead has a deep focus on HIV as well as hepatitis B and C.

When the technology was first discussed, Schulman stated, “People around the world depend on medications that require taking a pill every single day or even multiple times a day. That approximately 50 percent of patients in the developed world do not take their medicines as prescribed, a statistic that is even more challenging in the developing world, has a demonstrable effect on healthcare outcomes and a cost estimates to the U.S. healthcare system alone of over $100 billion annually. Lyndra’s long-acting technology should make a real dent in this protracted problem and help change the lives of millions of patients who feel tethered to the daily pill.”

https://www.biospace.com/article/gates-foundation-gilead-and-others-drop-55-million-on-series-b-for-lyndra-therapeutics/

Celgene Strikes Deal Worth Nearly $1 Billion for Blood Cancer Treatment

Celgene has struck another collaborative deal, even as the large pharmaceutical company is in the process of being folded into the operations of its new owner, Bristol-Myers Squibb.

This morning, privately-owned drug developer Triphase Accelerator, along with its majority shareholder FACIT, announced it had struck a collaborative deal with Celgene. The companies will harness their knowledge and resources to develop a first-in-class preclinical therapeutic targeting the WDR5 protein for the treatment of blood cancers including leukemia. The deal to develop TRPH-395, a novel small molecule inhibitor that disrupts WDR5 protein-protein interactions, could be worth up to nearly $1 billion.

Under terms of the deal, Celgene will pay Triphase $40 million in upfront funding. Celgene can then pay up to an additional $940 million if certain milestones are hit. The deal provides Celgene with an option to acquire RPH-395 from Toronto-based Triphase Accelerator.

According to Triphase, preclinical data for TRPH-395 showed that the compound demonstrated broad anti-proliferative activity across a wide range of cancer cell lines. Blood cancers like leukemia can result when WDR5-associated protein complexes are not appropriately regulated in the body. The WDR5 protein is critical for the formation and activities of certain protein complexes that are associated with DNA and indirectly modify genes. Drug compounds that can disrupt these cancer-causing cellular activities represent a novel therapeutic approach, which may also improve clinical outcomes in patients with solid tumors, Triphase Accelerator said in its statement.

The preclinical work with TRPH-395 was completed by Propellon Therapeutics, in conjunction with researchers at the Ontario Institute for Cancer Research. Propellon was also provided seed funding by FACIT. David O’Neill, president of FACIT, said Propellon was tasked with commercializing the preclinical TRPH-395 and multiple offers came through, with Celgene being the winner.

“The quality of the team and commitment by Triphase Accelerator to engage Ontario researchers and clinical sites in its high content studies, combined with its long-standing relationship with Celgene made this partnership the most compelling path to impact patients and the local economy,” O’Neill said in a statement.

Ilse Treurnicht, executive chairperson of Triphase, noted that the deal with Celgene is a significant milestone for the company. Treurnicht said Triphase is excited about the potential or realizing the vision of advancing the TRPH-395 program toward clinical proof of concept.

Celgene’s head of translational development Jorge DiMartino said the investment into the TRPH-395 program reflects the company’s “commitment to developing first-in-class epigenetic therapies for patients with hematological cancers.”

Since BMS announced it was acquiring Celgene for $74 billion earlier this month, the California-based company has continued to strike collaborative research deals. A little more than 10 days ago, Celgene struck deals with two companies to develop immuno-oncology treatments and cell therapies. Celgene entered into agreements with Boston-based Kyn Therapeutics to develop novel immuno-oncology therapies and also forged a collaborative effort to develop cell therapies that target cancer with Obsidian Therapeutics.

https://www.biospace.com/article/celgene-strikes-deal-worth-nearly-1-billion-with-triphase-accelerator-for-blood-cancer-treatment/

Takeda’s Phase 3 Vaccine Results ‘1 Step Closer’ to Stopping Dengue

Takeda Pharmaceutical announced that its vaccine for dengue fever hit its primary efficacy endpoint in its Phase III clinical trial.

Dengue fever affects as many as 400 million people annually, according to the U.S. Centers for Disease Control and Prevention (CDC). It is caused by one of four related viruses transmitted by mosquitoes. Symptoms usually start four to seven days after the mosquito bite and usually last three to 10 days. About 2.5 billion people, 40 percent of the world’s population, live where there is a risk of dengue transmission. About 20,000 people die each year from the disease.

Primary symptoms of dengue are high fever, severe headache, severe pain behind the eyes, joint pain, muscle and bone pain, rash, and mild blooding, usually from the nose or gums. At its worst, the capillaries start to leak, which allows the fluid in blood into the peritoneum and pleural cavity, which can lead to circulatory system failure and shock, followed by death.

TAK-003 is a tetravalent dengue vaccine based on a live-attenuated dengue serotype 2 virus. In Phase I and II trials, children and adolescents given the vaccine showed an immune response against all four dengue serotypes. It was found to be safe and well tolerated.

The Tetravalent Immunization against Dengue Efficacy Study (TIDES) Phase III trial showed the vaccine was efficacious in preventing dengue fever by any of the four serotypes. The TIDES trial is still ongoing and more results are expected later this year with data from other Phase III trials. The TIDES trial has enrolled more than 20,000 healthy children and adolescents from the ages of four to 16 years that live in dengue-endemic areas. The trial is in patients who have been exposed to dengue and who have not been exposed.

Rajeev Venkayya, Takeda’s president of the company’s Global Vaccine Business Unit, stated, “We are very encouraged by the performance of our dengue vaccine candidate in the study. This brings us one step closer to helping the world tackle the massive burden of dengue.”

The vaccine is administered in two doses three months apart. The first data about efficacy included 11 months of follow-up. The second part of the trial will include another six months of patient data and will review the vaccine’s performance in each of the four different serotypes in addition to how it affected people with previous exposure compared to those who are dengue-naïve.

That data will be used for regulatory filings. A third part of the trial will evaluate long-term safety by following participants for three more years.

The first dengue vaccine, Dengvaxia, was developed by Sanofi Pasteur and was first registered in Mexico in December 2015. Dengvaxia is a live recombinant tetravalent dengue vaccine. The World Health Organization (WHO) indicates there are at least five other vaccine candidates being studied in clinical trials.

There is some controversy related to Dengvaxia, at least in the Philippines, where the vaccine has been banned for the last year. The vaccine is not recommended for people who have been previously infected by dengue virus, and Sanofi Pasteur indicated in December 2017 that it planned to update its label.

A version of Dengvaxia is being evaluated by the U.S. Food and Drug Administration (FDA) under the name Dengaviia. It has a target action date of May 1, 2019.

In December, Merck and Co. signed a research collaboration deal with Instituto Butantan, based in Sao Paulo, Brazil, to develop vaccines against dengue virus disease. Merck and Instituto Butantan have licensed specific rights from the U.S. National Institutes of Health (NIH)’s National Institute of Allergy and Infectious Diseases (NIAID), related to the development of live attenuated tetravalent vaccines (LATV).

The Instituto Butantan also has a dengue vaccine candidate, TV003, which is in an ongoing Phase III clinical trial in Brazil. The trial expects to enroll almost 17,000 healthy individuals between the ages of 2 and 59 years in 15 cities. All patients in the trial will be monitored for five years by way of in-person visits to the health clinic and telephone or text communications.

https://www.biospace.com/article/takeda-s-phase-iii-dengue-results-bring-them-one-step-closer-to-stopping-tropical-disease/

Pfizer, Eli Lilly: Tanezumab 5mg met all 3 co-primary endpoints in Phase 3 study

Pfizer (PFE) and Eli Lilly and Company (LLY) announced top-line results from a Phase 3 study evaluating tanezumab 2.5 mg or 5 mg in patients with moderate-to-severe osteoarthritis pain. The tanezumab 5 mg treatment arm met all three co-primary endpoints at 24 weeks, demonstrating a statistically significant improvement in pain, physical function and the patients’ overall assessment of their OA compared to those receiving placebo. The tanezumab 2.5 mg treatment arm met two of the three protocol-defined co-primary efficacy endpoints compared to placebo, demonstrating a statistically significant improvement in pain and physical function, while patients’ overall assessment of their OA was not statistically different than placebo. Tanezumab is a humanized monoclonal antibody that is part of an investigational class of non-opioid pain medications known as nerve growth factor inhibitors. In this study, subcutaneous administration of tanezumab 2.5 mg or 5 mg was evaluated every eight weeks, for a total of 24 weeks, in patients with moderate-to-severe OA pain. Patients enrolled in the study had experienced inadequate pain relief from or intolerance to at least three different classes of analgesics, and on average had OA for more than six years. They also reported significant impact of their pain on their ability to function in everyday life. Preliminary safety data showed that tanezumab was generally well tolerated during the 24-week treatment period, with similarly low rates of treatment discontinuations due to adverse events observed among patients taking tanezumab and placebo. The trial also included a 24-week safety follow-up period, for a total of 48 weeks of observation.

https://thefly.com/landingPageNews.php?id=2854909