Eisai (ESALY) and Merck (MRK) announced that the European Commission has granted a marketing authorization for the oral receptor tyrosine kinase inhibitor LENVIMA as a single agent for the first-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma who have received no prior systemic therapy. Treatment options for this type of liver cancer are limited, and the prognosis is poor. LENVIMA is the first new, first-line treatment for advanced or unresectable HCC in a decade to show an overall survival treatment effect by statistical confirmation of non-inferiority against standard of care.
Thursday, August 23, 2018
Bluebird Bio and Gritstone Oncology partner to develop cancer cell therapies
bluebird bio and Gritstone Oncology will collaborate to research, develop and commercialize products for the treatment of cancer using cell therapy. Gritstone Oncology will leverage its proprietary Edge artificial intelligence platform to analyze specific tumor types to identify tumor-specific targets and natural T-cell receptors directed to those targets for use in bluebird bio’s established cell therapy platforms. bluebird bio will conduct all development, manufacturing and commercial activities. Gritstone Oncology will utilize its proprietary technology platform to enable patient selection for clinical development of such therapies. Gritstone Oncology will receive $20M in an upfront payment and an additional $10M in the form of a Series C preferred equity investment. In addition, Gritstone Oncology is eligible for significant development, regulatory and commercial milestones on any therapies, and tiered royalties on certain approved therapies.
Zogenix initiated at Ladenburg
Zogenix initiated with a Buy at Ladenburg. Ladenburg Thalmann analyst Michael Higgins started Zogenix with a Buy rating and $71 price target. The analyst believes the company will capitalize on ZX008’s “superior” epilepsy data.
Bristol-Myers’ lung cancer application granted Priority Review by FDA
Bristol-Myers (BMY) announced that the FDA accepted its supplemental Biologics License Application for Empliciti – elotuzumab – in combination with pomalidomide and low-dose dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The FDA granted the application priority review with an action date of December 27. The application is based on data from ELOQUENT-3, a randomized Phase 2 study evaluating the addition of Empliciti to pomalidomide and low-dose dexamethasone in patients with RRMM. Bristol-Myers Squibb and AbbVie (ABBV) are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.
What Can be Done About Rising ‘Deaths of Despair?’
“Deaths of despair” — lives lost to suicide, alcohol, or drug use — have risen in the U.S., and have contributed to the nation’s lower life expectancy, according to data discussed at a Wednesday briefing by the Alliance for Health Policy and the Commonwealth Fund.
Life expectancy in the U.S. dipped in 2016 to 78.6 years from 78.7 years in 2015, according to the CDC National Center for Health Statistics (NCHS). The trend signals the first year-over-year decline in life expectancy at birth since the 1960s.
If these trends continue, as early mortality data from the CDC suggests they may, average life expectancy will have fallen for 3 years consecutively for the first time since the 1918 “Spanish flu” epidemic, noted David Radley, PhD, MPH, a senior scientist at the Commonwealth Fund, and senior study director at Westat, a research agency.
The term “deaths of despair “was coined by Princeton University economists, and such causes of death have risen 51% nationally from 2005 to 2016, explained Radley, who co-authored The 2018 Scorecard on State Health System Performance.
Drug overdoses, including but not limited to deaths from opioids, are seen as the primary driver of such deaths, he stated.
Radley also noted striking variations in these deaths across the country. In 2016, West Virginia had the highest rate of deaths from drugs, alcohol, or suicide at about 83 per 100,000 people. Nebraska showed the lowest increase in rates of death in these categories with about 29 deaths per 100,000.
While heart disease and cancer are responsible for far more deaths than suicide, alcohol, or drug use, “what’s unique about these deaths of despair is that it’s the only leading cause of death that’s actually increasing,” he said, and increases are seen in every state.
At the county level, Marvin Figueroa, deputy secretary of health and human resources for the Commonwealth of Virginia noted that certain social determinants of health factor into the markedly higher rates of drug drug overdoses in some pockets of the country. For example, the Southwestern and Eastern corners of Virginia have higher rates of poverty and unemployment, and lower rates of high school graduation, than other areas of the state.
To address the opioids epidemic, Radley suggested increasing access to naloxone, curbing the opioid prescription rate, and expanding access to care delivery models that integrate behavioral health care into primary care.
Figueroa noted the progress Virginia has seen since implementing the Addiction and Recovery Treatment Services (ARTS) program in April 2017.
Treatment rates for Medicaid enrollees with substance use disorders increased 64%; the number of enrollees given pharmacotherapy for opioid use disorders rose 34%; and the number of practitioners offering outpatient psychotherapy or counseling more than doubled, he stated.
Briefing panelists also discussed the challenge of expanding access to buprenorphine. Anand Parekh, MD, chief medical advisor for the Bipartisan Policy Center, questioned the rationale behind requiring physicians to take an 8-hour training, and for non-physicians (physician assistants and nurse practitioners) a 20-hour training before being allowed to prescribe buprenorphine.
Richard McKeon, PhD, chief of the Suicide Prevention Branch for the the Substance Abuse and Mental Health Services Administration (SAMHSA), highlighted worrisome trends in suicide rates. From 1999 to 2016, in half of all U.S. states, suicide rates have risen 30%, he said. An estimated 45,000 people died from suicide in 2016.
Suicide is now the second leading cause of death for people, ages 10-30, according to the CDC National Vital Statistics System, he noted.
Sometimes, it can be hard to distinguish between an accidental overdose death and an intentional suicide, McKeon pointed out. Anecdotally, he said he has spoken with clinicians who have saved patients with naloxone, and then been told by those patients “I wish you hadn’t brought me back.” Still, there has not been significant research in this area, McKeon noted.
One of the most challenging aspects of suicide prevention is ensuring that people who’ve attempted suicide aren’t lost in a transition, for example from the emergency department to an outpatient program. Research has shown this is a period of heightened risk, McKeon told MedPage Today after the briefing.
“Suicide risk is not on or off, it’s on a continuum … which means that rapid treatment is important,” he said, adding that one way to address this problem is with telephone-based follow-up.
The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) and SAFE VET evaluation programs have shown reduced suicidal behavior among suicidal people, after discharge using this telephonic approach. A similar study at the Department of Defense used text messaging.
McKeon also highlighted the“Perfect Depression Care” initiative at the Henry Ford Health System. Core pillars of the program include increasing access to care and preventing access to lethal means of suicide. The program also employs “drop-in group visits, same-day evaluations by a psychiatrist, and department-wide certification in cognitive behavior therapy,” according to a case study in NEJM Catalyst.
This “zero suicides” strategy has gained attention following an endorsement in the 2012 Surgeon General’s National Strategy for Suicide Prevention report.
Cantor Fitzgerald Starts Reata Pharmaceuticals (RETA) at Overweight
Cantor Fitzgerald analyst Charles Duncan initiates coverage on Reata Pharmaceuticals.
Wednesday, August 22, 2018
A Glimpse into the Pancreatic Cancer Pipeline
The passing of singing great Aretha Franklin has focused attention on pancreatic cancer. Franklin, 76, succumbed to a neuroendocrine tumor of the pancreas. According to the National Cancer Institute (NCI), pancreatic cancer is relatively rare, with about 55,440 cases diagnosed annually, representing about 3.2 percent of new cancer cases. But each year, 44,330 Americans die from the disease, or about 7.3 percent of cancer deaths. And it’s a tough cancer to beat, with only 8.5 percent surviving for five years.
One problem is, like cancer itself, pancreatic cancer is not a single disease. Anirban Maitra,scientific director of the Sheikh Ahmed Pancreatic Cancer Research Center at theUniversity of Texas MD Anderson Cancer Center, told Forbes, “The first thing to do if somebody gets a diagnosis of pancreatic cancer is to know what they are dealing with. Because everything they deal with will change dramatically based on that.”
Forbes points out that neuroendocrine tumors, the type that Aretha Franklin had, as did Applefounder Steve Jobs, are the rarer type of pancreatic cancer. Forbes writes, “Afinitor, a drug made by Novartis, has been shown to help patients whose neuroendocrine tumors have spread outside the pancreas, increasing the time before their tumors grow by six months, to 11.5 months. In a clinical trial, patients who got Afinitor did not live longer than those who received placebo; this may be because the study allowed patients in the placebo group to get the drug once their tumors start to grow.”
For patients with the more common form of pancreatic cancer, adenocarcinoma, the prognosis is worse. Famous people who died from adenocarcinoma include Dirty Dancing actor Patrick Swayze and opera singer Luciano Pavarotti. For these types, there are typically two chemotherapy regimens, one a combination of Gemzar and Abraxane, and the other a mixture of drugs called FOLFIRINOX. They extend survival from about four months to nine months in the average patient.
Maitra points out that surgical removal when the tumor is small gives the best odds of survival.
If one problem is the type of cancer, early detection is another. Pancreatic cancer is one of those types of cancer that is typically diagnosed from symptoms—abdominal pain, jaundice, weight loss, for example, in many cases. And by that time, the cancer has often spread, and surgery is not an option. Diagnosis is performed using a CT scan or an invasive procedure, such as a needle biopsy and invasive ultrasound.
In March 2018, OncLive discussed pancreatic cancer drugs currently in the pipeline with Tanios Bekaii-Saab, professor of medicine at Mayo Clinic. He noted, “Over the last few years, we have developed new strategies to extend survival for our patients. Half of the patients are crossing the one-year survival line, with 25 percent crossing the two-year survival line. We have patients who survive, three, four, and five years, but it is less than 5 percent of patients. However, this would be unheard of five or six years ago, so we are doing better. We are on the right path to ultimately bring pancreatic cancer into the mainstream.”
He notes there are two primary pathways for treating pancreatic cancer. The first is gemcitabine and Abraxane (nab-paclitaxel). When that fails, they receive 5-fluorouracil (5-FU) and MM-398 (irinotecan liposomem injection; Onivyde) based on the NAPOLI-1 trial. For the third-line setting, they try a platinum-based approach, such as FOLFOX or cisplatin.
Bekaii-Saab notes that genetic understanding of the disease is improving, and along with that understanding, some successes with new therapies have been seen. “For patients with microsatellite instability-high (MSI-H) tumors, immunotherapy works best. That subgroup was included in the study that led to the approval of pembrolizumab (Keytruda) in MSI-H cancers. There were a few patients with pancreatic cancer who had incredible responses. One patient continues to be in a complete remission from that treatment.”
That’s a rare subset of pancreatic cancers. Another group has BRCA1/2 and PALB2 mutations and homologous recombination deficiency (HRD). Bekaii-Saab says that platinum-based treatment and PARP inhibitors are showing promise for treating these subgroups. “The three PARP inhibitors that have been studied the most are veliparib, olaparib, and rucaparib. Veliparib appears to be the least potent. There are rare reports of any single-agent activity of this drug in pancreatic cancer…. The other two PARP inhibitors, olaparib and rucaparib, have shown single-agent activity in refractory patients. I don’t believe that single-agent PARP inhibitors are going to be the answer for an aggressive disease like pancreatic cancer, but they would be optimally combined for maintenance phases.”
He believes that combining these drugs with irinotecan-based compounds and then a liposomal irinotecan or platinum-based drug might be a good approach.
There are also at least two other approaches and drugs that show promise, Bekaii-Saab says. “The first is PEGPH20, which is an agent that targets the stroma and hyaluronan (HA). It breaks down that stroma to allow chemotherapy into the tumor to maximize the kill. It is a great concept and looks very promising.” PEGPH20 is being developed by Halozyme Therapeutics.
And finally, Bekaii-Saab brings up napabucasin (BBI-608), a stem cell inhibitor under development by Boston Biomedical. “Napabucasin seems to inhibit and facilitate killing lowering the chemosensitizing capacity against these pancreatic cancer cells. If you give it with chemotherapy and gemcitabine, nab-paclitaxel, or paclitaxel, you seem to kill those cancer cells more efficiently and prevent them from reverting to the stemless phenotype.”
As frustratingly slow as treatments for this rare cancer may be, there are signs of progress.
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