A system that allows intracoronary delivery of blood “supersaturated” with oxygen after coronary stenting has received market approval from the US Food and Drug Administration (FDA), the developer, Therox, announced today.
The SuperSaturated Oxygen (SSO₂) therapy system, indicated for use immediately after stenting for acute ST-segment elevation myocardial infarction (STEMI) in the left-anterior-descending (LAD) coronary artery, aims to limit the extent of acute myocardial ischemia and therefore final infarct size.
The system combines oxygen-supersaturated saline with autologous blood, which is delivered over 60 minutes starting immediately after stenting opens the artery. “The superoxygenated blood helps reduce capillary swelling to restore blood flow to surrounding tissue and decrease infarct size,” according to the company.
The FDA approval marks 10 years since an FDA advisory committeerecommended against the system’s approval, in part to await further safety and efficacy data after clinical end-point concerns in the AMIHOT 2 study, which had been presented in 2007.
A combined analysis of that trial and the preceding AMIHOT trial, as previously reported here, suggested a significant reduction in infarct size by Tc-99m sestamibi single-photon-emission computed tomography (SPECT) 2 weeks after the procedure using SSO₂, compared with a control group, in the patients with large anterior STEMI.
But in AMIHOT 2, there was also a trend toward more major adverse cardiac events (MACE) in the group that received the supersaturated blood treatment.
More recently, the 2018 Intracoronary Hyperoxemic Oxygen Therapy in Anterior Acute Myocardial Infarction (IC-HOT) study provided more safety data. It suggested the SSO₂ therapy was safe in 100 patients with STEMI and left-main coronary culprit arteries, finding no elevated risk for a primary end point of death, reinfarction, clinically driven target-vessel revascularization, stent thrombosis, severe heart failure, or TIMI major or minor bleeding.
A federal judge on Friday said he wants to hear in court from witnesses who object to the Justice Department’s decision last year to approve CVS Health Corp.’s nearly $70 billion acquisition of Aetna Inc.—a highly unusual move that threatens to shake up the already-consummated deal.
U.S. District Judge Richard Leon in Washington, D.C., is reviewing a department settlement last fall that allowed the merger after the companies agreed to sell off assets related to Medicare drug coverage.
“This is a matter of great consequence to a lot of people,” Judge Leon said during a brief court hearing. Health care “is a high priority issue for tens of millions of families,” he added. The judge, a George W. Bush appointee, last December said he was concerned the department hadn’t adequately addressed broader potential competitive harms raised by the merger.
At the time, he didn’t halt CVS’s CVS, +1.24% integration of the Aetna assets but made clear he wanted to spend additional time considering the settlement. CVS had volunteered to Judge Leon that it would keep parts of its Aetna operations separate until he did so.
A federal law called the Tunney Act requires the government to have proposed merger settlements approved by a federal court, which determines whether the deal is in the public interest.
The University of Texas Health Science Center at San Antonio is starting an internal accelerator program for inventors who work at the institution, with the goal of picking a first group of five to eight prospective entrepreneurs around May.
The accelerator, which UT Health is calling TechNovum, will run its first program from June through October and will conclude with two days of presentations for the researchers to pitch the products they’ve developed. The program will include training on market validation, developing a business plan, and mentoring on making a pitch to investors, among other training.
TechNovum is going to be operated as a part of UT Health’s office of technology commercialization, which will take applications from inventors whose products have already gone through the office’s standard validation process. When a UT Health faculty member alerts the office of an invention that has potential to be commercialized, the office runs the product through 12 weeks of analysis—both product and market validation called a technology management report—to help the inventor and university determine if they might want to license the invention or maybe develop a startup out of it.
Inventors who get a favorable report will be eligible for the accelerator, said John Gebhard, the assistant vice president for the commercialization office. John Fritz and Sean Thompson, who both work out of the commercialization office with a focus on bringing inventions to market, will be co-directors of the accelerator. The program is an effort to formalize business, marketing, and entrepreneurial training that the office previously did on an ad-hoc basis, Fritz said during an interview yesterday at the university.
“Doing this is more efficient than what we’ve had to do, which was more one-on-one, individual mentoring,” Fritz said.
Because most of the inventions are so early stage, the accelerator may focus on different subjects than other accelerators for more advanced companies, such as Houston’s TMCx for health IT and medical devices, Techstars on the tech side of the startup world, or incubators like JLabs. San Antonio has other accelerator and startup programs, including a couple run by VelocityTX, which operates a “pre-accelerator” and another accelerator for international companies considering a move to the US, neither of which are solely focused on life sciences.
TechNovum will use a curriculum developed by business coach Wendy Kennedy (VelocityTX uses the same curriculum), which aims to help potential entrepreneurs figure out things like market fit and competitive edge. Fritz said the TechNovum will offer additional mentorship on issues specific to UT Health researchers who are developing products related to life sciences, such as manufacturing and quality control, regulatory matters, reimbursement, and partnering a product.
UT Health also plans to bring in outside mentors from the business community to talk to the group of researchers whose products are picked for the accelerator. Thompson, the other co-director, said the accelerator is an effort to make practical use out of research done by faculty at the university.
“There’s some people who might get bothered about this focus on commercialization,” Thompson said during the interview at the commercialization office. “Basic research is absolutely necessary, but research by itself, alone, has never saved anyone’s life. It’s the use of what you learn from that basic research and the application of that that is really most important.”
More than half of older patients with untreated acute myeloid leukemia (AML) had rapid attainment of complete remission with the combination of venetoclax (Venclexta) and low-dose cytarabine, data from a single-arm clinical trial showed.
The regimen led to complete remission with or without blood-count recovery in 44 of 82 patients, with a median time to first response of 1.4 months. The cohort had a median response duration of 8.1 months and median overall survival (OS) of 10.1 months.
Patients without prior exposure to hypomethylating agents (HMAs) had a higher response rate, longer response duration, and better survival, Andrew H. Wei, MD, PhD, of the Alfred Hospital in Melbourne, Australia, and co-authors reported online in the Journal of Clinical Oncology.
“The high remission rate, low early mortality, rapid induction of remission, and durable length of remission make the combination with venetoclax an attractive and novel treatment option for older adults not suitable for intensive chemotherapy,” the authors concluded.
The results added to preliminary findings reported at the 2017 American Society of Hematology meeting. Last last year, the FDA approved the venetoclax-cytarabine combination for older patients with AML. Supporting data for the application included the study conducted by Wei and colleagues.
“Some of these patients can have durable responses that can be extended for a long period of time,” said co-author Stephen A. Strickland Jr., MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. “This is something we haven’t seen a whole lot of in this patient population.”
Patients with newly diagnosed AML have a median age of 68 and often are ineligible for intensive chemotherapy, leaving them with few effective less-intensive options. Partly because of limited expectations for treatment success, many older patients with AML do not receive leukemia treatment, the authors noted.
Members of the B-cell leukemia/lymphoma-2 (BCL-2) family promote cell survival in cancer cells, and BCL-2 mediates chemoresistance and enhances leukemic blast and progenitor cells, Wei and co-authors continued.
Venetoclax, a selective oral BCL-2 inhibitor, achieved an objective response rate of 19% as single-agent therapy for patients with heavily pretreated AML. Resistance to the drug may be mediated by pro-survival proteins, such as MCL1, which is downregulated by HMAs and cytarabine, both of which worked synergistically with venetoclax against AML in preclinical studies. A preliminary clinical trial of venetoclax combined with an HMA showed a 61% complete response rate in older patients with untreated AML.
For the current study, Wei and colleagues reported findings from a prospective phase Ib/II clinical trial involving patients ≥60 with untreated AML. The treatment regimen consisted of venetoclax 600 mg/day and subcutaneous low-dose cytarabine (20 mg/m2 on days 1 and 10 of 28-day cycles). Outcomes of interest included safety, tolerability, response rate, duration of response, and overall survival.
The study population had a median age of 74, 49% had secondary AML, 71% had prior HMA treatment, and 32% had poor cytogenetics. During the dose-escalation phase of the trial, no dose-limiting toxicities occurred at the phase II dose of 600 mg/day.
The most commonly reported grade ≥3 adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and decreased white blood cell count (34%). The most common nonhematologic adverse events (all grades) were nausea (70%), diarrhea (49%), hypokalemia (48%), and fatigue (43%).
The authors reported that 45 patients had venetoclax dose interruptions related to adverse events, most often between 28-day cycles because of delayed neutrophil and platelet recovery. Six patients required venetoclax dose reductions, primarily because of thrombocytopenia.
The 54% rate of complete remission included remission with incomplete hematologic recovery in 28%. The highest rates of complete response occurred in patients with de novo AML, with intermediate-risk cytogenetics, and with no prior HMA exposure (71%, 63%, 62%, respectively). Patients with no prior HMA exposure had a median response duration of 14.8 months and median overall survival of 13.5 months.
Patients who achieved a complete response with or without complete hematologic recovery had an estimated 12-month survival of 73%, as compared with 5% for patients who had no response. The 12-month OS was 100% for patients who had complete response with hematologic recovery and 49% for those who had complete response with incomplete recovery. Most patients who achieved remission became transfusion independent.
Strickland said the “impressive” results compare favorably with reported outcomes achieved with intensive chemotherapy.
“The results with this regimen and with venetoclax and hypomethylating agents look just as good or maybe even better than some intensive approaches,” said Strickland. “The question we’re now having to ask … is should we be changing the paradigm of treatment and looking for lower-intensity therapy first.”
“That’s obviously very controversial and we don’t have head-to-head studies of the less-intensive route versus more intensive treatment options. I think the next step is to try and figure out whether we can do just as well with a low-intensity approach or what is the role or best-identified population for less-intensive therapy.”
AbbVie and Genentech provided financial support and participated in the design, study conduct, and interpretation of data, as well as writing, review, and approval of the manuscript.
Wei disclosed relationships with Amgen, Servier, Novartis, Celgene, AbbVie, Roche/Genentech, Pfizer, and Janssen. Multiple co-authors disclosed relationships with the pharmaceutical industry and other commercial interests.
After attesting to its use in ovarian, breast and pancreatic cancers, the trio of AstraZeneca, Merck & Co. and Myriad Genetics is now bringing the latters companion diagnostic to bear on metastatic castration-resistant prostate cancer.
In a phase 3 study, the BRACAnalysis CDx precision medicine test will be used to hunt for germline BRCA mutations in men eligible for the Big Pharmas PARP-inhibiting Lynparza therapy.
The clinical trial, estimated to wrap up in early 2021, could form the basis of an expanded premarket approval for the BRACAnalysis test in the population, according to Myriad.
AstraZeneca first began working with Myriad on Lynparza in 2007, and has since helped garner U.S. and Japanese approvals for the in vitro diagnostic in ovarian and breast cancersstarting in December 2014, when BRACAnalysis CDx became the first laboratory-developed test approved by the FDA.
Most recently, Japans Ministry of Health, Labour and Welfare approved the blood test in February as a companion diagnostic for first-line Lynparza maintenance therapy in advanced ovarian cancer. The FDA approved BRACAnalysis CDx in a similar indication last December in patients showing a complete or partial response to treatment with platinum-based chemotherapy.
But while the collaboration has led to advances in ovarian and breast cancer, there is a significant unmet medical need in men with metastatic castration-resistant prostate cancer and BRCA1/2 mutations, which is an area where the utility of PARP inhibitors is being explored,” Nicole Lambert, president of Myriad Genetics, said in a statement.
Another area is metastatic pancreatic cancer, where Lynparza and the BRACAnalysis test recently demonstrated positive results in a phase 3 study of patients with germline BRCA mutations following platinum-based chemotherapy.
While Lynparza was beating placebo in progression-free survivaland as the drug moves closer to becoming the first PARP inhibitor approved in pancreatic diseaseMyriads diagnostic showed it could successfully identify patients that would benefit from the treatment, and the company said it plans to file a supplementary approval application with the FDA.
Pfizers Vizimpro, a drug that could challenge AstraZenecas fast-growing Tagrisso in lung cancer, has been approved for marketing by the European Commission.
Vizimpro (dacomitinib) has been approved in the EU as a first-line, single-agent therapy for locally advanced or metastatic EGFR-positive non-small cell lung cancer (NSCLC), a similar indication to that cleared by the FDA last September.
Dacomitinib has been held up on its way to market significantly, mainly because two phase 3 trials of the drug reported in 2014, which assessed the drug as a second- or third-line treatment option in NSCLC, failed to hit the mark.
Undeterred, Pfizer ran a third trial called ARCHER 1050 that showed Vizimpro was able to extend progression-free survival (PFS) compared to AZs first-generation EGFR inhibitor Iressa (gefitinib), although it was associated with greater toxicity, including skin reactions and diarrhoea.
Now, with approval on both sides of the Atlantic, the drug can mount a stronger challenge against Tagrisso (osimertinib), Iressa, and other EGFR-targeted drugs including Roche/Astellas first-generation drug Tarceva (erlotinib) and Boehringer Ingelheims second-generation Giotrif (afatinib) in the market.
Tagrisso billed as a third-generation drug is already dominating the second-line EGFR-positive NSCLC market, with sales almost doubling to $1.86bn last year and the brand looking likely to become AZs biggest seller in 2019. AZ has been working hard to push Tagrisso into the first-line setting however, based on the results of its FLAURA trial, and seems to be making progress on that front.
Pfizers global president of oncology, Andy Schmeltz, told the Cowen & Co conference last month that there is still plenty of unmet medical need in the EGFR-positive NSCLC category, as the five-year survival rate is still only about 12%.
He acknowledged that the market is very competitive, but suggested Pfizer would be able to position Vizimpro as a first-line option that could then be followed by other EGFR-targeted drugs.
There is one factor that could make that slightly tricky though. The ARCHER 1050 trial design excluded patients with brain metastases, which is a common feature of this patient population, and AZ makes much of Tagrissos ability to cross the blood-brain barrier.
Meanwhile, the hope had been that one of the pivotal trials of Tagrisso and Vizimpro in first-line NSCLC would show a significant impact on overall survival (OS), a secondary endpoint, to help select a preferred option. As it has turned out, neither drug has been able to show a statistically significant on that measure so far.
There is however still some debate about the best order to deliver these drugs, as all EGFR inhibitors eventually succumb to resistance and lose their efficacy over time, and some oncologists have argued Tagrisso should be held in reserve rather than given first-line.
For Pfizer, the Vizimpro approval is another pillar in its bid to rebuild its oncology franchise that has been hit hard by competition to Xalkori (crizotinib) for ALK-positive NSCLC from Roches Alecensa (alectinib), Novartis Zykadia (ceritinib), and Takedas Alunbrig (brigatinib).
Last November, the drugmaker claimed FDA approval for Xalkori follow-up Lorbrena (lorlatinib) in second-line ALK-positive NSCLC and SMO inhibitor Daurismo (glasdegib) for acute myeloid leukaemia, while in October it got a green light for PARP inhibitor Talzenna (talazoparib) for advanced breast cancer.
