Alector, AbbVie Initiate Phase 1 for Treatment of Patients with Alzheimer’s

Alector, Inc. (Nasdaq:ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, a novel therapeutic approach for the treatment of neurodegeneration, today announced the initiation of the first-in-human Phase 1 trial for AL003, called the INTERCEPT study. The study is initially investigating the safety profile, pharmacodynamics and target engagement of AL003 in healthy volunteers. AL003 is the company’s second product candidate being developed for the treatment of patients with Alzheimer’s disease in collaboration with its partner AbbVie.

Alector is focused on identifying and functionally repairing genetic mutations that cause dysfunction of the brain immune system leading to neurodegeneration. Genetic mutations in the SIGLEC 3 receptor, which is expressed on the brain’s microglia cells, were shown to increase the risk of developing Alzheimer’s disease by inhibiting the beneficial activity of the brain’s immune system.

“We designed AL003 to functionally counteract the SIGLEC 3 risk allele,” said Arnon Rosenthal, Ph.D., co-founder and chief executive officer of Alector. “AL003, which blocks the function of SIGLEC 3, an inhibitory receptor on the microglia, conceptually acts in a similar manner to PD1 inhibitors in oncology, which block the function of an inhibitory receptor on T cells. Blocking SIGLEC 3 will enable a more robust brain immune system that can better address multiple disease-causing pathologies. and we expect this will lead to slowing or stopping of disease progression in patients with Alzheimer’s disease.”

https://www.nasdaq.com/press-release/alector-initiates-phase-1-trial-of-al003-for-the-treatment-of-patients–with-alzheimers-disease-20190401-01196

Aveo, Biodesix report ‘positive’ results from ficlatuzumab-cytarabine trial

AVEO Oncology and Biodesix, Inc. announced results from an investigator-sponsored Phase Ib expansion cohort of ficlatuzumab, AVEO’s potent hepatocyte growth factor inhibitory antibody product candidate, in combination with cytarabine in patients with relapsed and refractory acute myeloid leukemia. The results were presented in a poster session at the American Association for Cancer Research 2019 Annual Meeting. The presentation, titled, “CyFi: Results from a phase Ib expansion cohort of ficlatuzumab combined with high-dose cytarabine in patients with high risk relapsed or refractory acute myeloid leukemia” is available in the Publications & Presentations section of AVEO’s website. Elevated serum HGF level is an adverse prognostic factor associated with worse survival in AML and other cancers. Pre-clinical models have shown that myeloid blasts produce HGF and that blocking the HGF/c-Met pathway sensitizes blasts to cell death. The Phase Ib trial, which was funded by Gateway for Cancer Research and is being conducted at the UCSF Medical Center under the direction of Charalambos Andreadis, M.D., Associate Professor of Clinical Medicine, Director, Clinical Research Support Office, UCSF Helen Diller Family Comprehensive Cancer Center, was designed to assess the safety, tolerability and preliminary efficacy of ficlatuzumab with cytarabine in AML patients who are refractory to first line therapy or have relapsed within one year of induction, a population known to have poor outcomes. The maximally tolerated dose was 20 mg/kg of ficlatuzumab on day 1 followed by 2 g/m2 cytarabine daily on days 2-7. Of 12 patients who received ficlatuzumab and cytarabine at the maximally tolerated dose, one of whom was non-evaluable, 6 achieved a complete response. Of 18 patients enrolled in the study, 17 were evaluable and 9 achieved a CR. The most frequent grade 3/4 treatment emergent adverse events observed were febrile neutropenia, LFT abnormalities, and electrolyte disturbance. There was one death from sepsis and multi-organ failure that was determined to be disease related, and one patient withdrew from the study due to grade 4 gastrointestinal bleed, determined to be likely ficlatuzumab related. scRNA sequencing identified a TNF alpha and IFN gamma inflammatory signature that correlated with response to ficlatuzumab at count recovery.
https://thefly.com/landingPageNews.php?id=2886987

Apyx pulls application for premarket notification 510k submission to FDA

Apyx Medical Corporation announced it has voluntarily withdrawn its application for premarket notification 510k regulatory clearance of J-Plasma/Renuvion for use in dermal resurfacing procedures. The company will continue to work with the U.S. Food and Drug Administration relative to the development of a new 510k submission. At the present time, the company cannot provide a timeline for resubmission but intends to do so after further discussions with the Agency.
https://thefly.com/landingPageNews.php?id=2886991

RA Pharma: Phase 2 zilucoplan trial data selected for presentation

Ra Pharmaceuticals, Inc. announced that data from its Phase 2 clinical trial of zilucoplan for the treatment of generalized myasthenia gravis have been selected for an Emerging Science dual oral and poster presentation at the 2019 American Academy of Neurology Annual Meeting in Philadelphia, PA, from May 4 to 10, 2019. The presentation will feature data from the Phase 2, randomized, double-blind, placebo-controlled clinical trial, as well as data from the open-label, long-term extension study.

https://thefly.com/landingPageNews.php?id=2886994

BeiGene presents Phase 1 tislelizumab data at AACR

BeiGene announced the presentation of long-term Phase 1 data and results of structural and binding mechanistic analyses on its investigational anti-PD1 inhibitor, tislelizumab, in posters at the American Association for Cancer Research, or AACR. The multi-center, open-label Phase 1 trial of tislelizumab as monotherapy in advanced solid tumors is being conducted in Australia, New Zealand, the United States, Taiwan, and South Korea and consists of dose escalation, schedule expansion, fixed dose expansion and indication expansion. This first-in-human, or FIH, trial is fully enrolled with over 450 patients. As of October 27, 2018, 65 patients received tislelizumab for more than 12 months and were included in this long-term exposure, or LTE, analysis. These 65 patients were from both the dose-escalation and dose-expansion phases. Most patients with LTE received tislelizumab at 5 mg/kg Q3W, while additional patients received 2 mg/kg Q3W, 2 mg/kg Q2W, 5 mg/kg Q2W and 200 mg Q3W. The most common tumor types were non-small cell lung cancer, hepatocellular cancer and bladder and ovarian cancers. With a median follow-up of 27.2 months, the objective response rate, or ORR, among patients with LTE was 68%. Four patients achieved complete response, including patients with cutaneous squamous cell carcinoma, endometrial, bladder and esophageal cancers. All four patients were PD-L1 positive. Partial responses and stable disease were observed in both PD-L1 positive and PD-L1 negative tumors. The median duration of response was 21.1 months in those with LTE. LTE to tislelizumab was generally well-tolerated when given for more than 12 months. As of the data cutoff, 52 of 65 patients experienced one or more treatment-related adverse event, or TRAE, most of which were mild to moderate in severity. Rash was the only TRAE reported in more than 15% of patients, and no rash event of grade 3 or higher occurred. Serious TRAEs occurred in three patients, including pyrexia and arthritis and all resolved. Three patients experienced AEs that eventually led to discontinuation. There were no fatal AEs.

https://thefly.com/landingPageNews.php?id=2886995

Pharma spends big as Massachusetts lawmakers review drug-pricing bills

State legislators in Massachusetts are preparing to review a slew of bills aimed at state-level drug pricing, and the pharmaceutical industry is opening its checkbook to fight back.

The state’s Joint Committee on Health Care Financing on April 11 will examine 21 bills targeting price transparency and affordability for patients. State Sen. Cindy Friedman, the committee chair, told the Boston Herald that lawmakers will take a hard look at measures to open up drugmakers’ pricing secrets and lower sticker prices for patients.

“Drugs are a huge contributor to health care costs, and it’s becoming, as many other parts of health care, more and more of a crisis in terms of people’s ability to pay for their health care,” Friedman said.

But pharmaceutical companies aren’t taking that challenge sitting down.

In 2018, drugmakers spent more than $4 million lobbying the Massachusetts statehouse, the Herald reported. One of the biggest players in the lobbying effort, the Pharmaceutical Research Manufacturers of America (PhRMA), told FiercePharma that the state’s push to cap prices would keep patients from getting the drugs they need.

“We oppose government price-setting proposals in the states,” spokeswoman Priscilla VanderVeer said. “Government price controls limit access to medicines for patients and they stifle new innovation.”

PhRMA itself spent $292,836 lobbying Massachusetts lawmakers in 2018, the Herald said. VanderVeer declined to comment on the group’s lobbying strategy.

The push by Beacon Hill lawmakers is not the first attempt to give Massachusetts more control over drug pricing, just as states such as Nevada and California have done.

In 2017, Massachusetts pushed for power to use formulary negotiations to manage its drug costs, but was rebuffed by Tim Hill, then-acting director of the Center for Medicaid and CHIP Services. The state wanted to adopt tactics similar to those used by private insurers and pharmacy benefits managers, but Hill said the plan did not meet CMS requirements that prevent Medicaid programs from managing coverage.

State legislators also pushed for a pricing transparency bill in early 2016 that Jonathan Fleming, general partner of biotech investment firm Oxford Bioscience Partners, called “a nightmare” in a committee hearing. The bill later fizzled out in early 2017.

The state’s drug pricing battle comes as President Donald J. Trump and the pharmaceutical industry continue their impasse at the federal level.

Last May, Trump outlined a plan that would push companies to lower prices by stepping up negotiations and competition, and providing incentives to lower list prices and cut out-of-pocket costs for patients. Pharma responded with widespread price hikes in January, upping the cost of more than 250 drugs, Reuters said.

Despite that setback, federal lawmakers are pushing ahead with measures in both houses of Congress. Most recently, Sen. Rick Scott, R-Fla., announced a Transparent Drug Pricing Act that would cap U.S. prescription drugs at the same list price as other developed nations, among other measures.

https://www.fiercepharma.com/pharma/pharma-spends-big-as-massachusetts-lawmakers-review-drug-pricing-bills

Piper Jaffray sees Endologix’s updates as ‘positive’

Piper Jaffray analyst Matt O’Brien maintained a Neutral rating on Endologix, saying he wanted to see “more evidence of execution in the coming quarters.” The analyst added that the updates the company released this morning, including an equity raise, an exchange of convertible debt, a number of updates with the Deerfield agreement, and a reaffirmation of its FY19 revenue guidance, were a “positive,” as it showed the company has “increased financial flexibility lower debt load risk, and easier covenants.”

https://thefly.com/landingPageNews.php?id=2886887