Pick Your Battles

Lifted from Fierce-BIO Gilead has posted subpar data from two Phase III trials of JAK inhibitor momelotinib in patients with the bone marrow disorder myelofibrosis, continuing its struggles in the clinic. The data raise doubts about momelotinib’s ability to hold its own against Incyte’s Jakafi, let alone unseat the blockbuster incumbent. One of the Phase III trials pitted momelotinib against Jakafi in previously-untreated myelofibrosis patients. That study met its primary endpoint of noninferiority to Jakafi in terms of splenic response rates, defined as a reduction in spleen volume of 35% or more. Such declines were achieved by 26.5% of subjects in the momelotinib arm, compared to 29% in the Jakafi cohort. Momelotinib fared worse against a key secondary endpoint that looked at symptom scores for the myeloproliferative neoplasms that affect myelofibrosis patients. Failure to match Jakafi in symptom scores prompted Gilead to scrap plans to formally analyze three anemia-related secondary endpoints, despite a glance at the data suggesting momelotinib bested its rival against these measures. When Gilead acquired momelotinib in its $510 million takeover of YM Biosciences, the potential for the JAK inhibitor to control anemia was seen as giving it an edge over Jakafi, the effect of which is limited to reductions in spleen size. The second trial gave momelotinib or best alternative treatment (BAT) to myelofibrosis patients who had previously received Jakafi. Gilead was hoping to show momelotinib triggered greater splenic response rates than BAT, but the JAK inhibitor failed to deliver. Momelotinib appears to compare favorably to BAT in terms of symptom scores and the anemia-related endpoints, but having missed the primary goal Gilead again opted against performing formal sequential statistical testing. Gilead plans to discuss the data with regulators before deciding how to proceed. But, even if the noninferiority result is enough to get momelotinib approved, the top-line data are bereft of reasons to think the JAK inhibitor can steal market share from Jakafi. If momelotinib is ultimately chalked up as a failure, it will join a fast-growing list of clinical setbacks for Gilead. In 2016, Gilead has delivered weak data from trials of cardiovascular candidate eleclazine, ulcerative colitis hopeful GS-5745 and repeat-failure simtuzumab. The string of failures has ratcheted up pressure on Gilead to wheel and deal its way to a stronger pipeline. Or, as Barclays Analyst Geoff Meacham understatedly put it: “Given that the internal pipeline is struggling to produce candidates that could provide a significant offset to the projected decline in HCV sales, we think external deployment of capital in a deal will be favorably received by investors.” Read more

The Upside is that At least there is a Theory

n Alzheimer’s disease, the interaction between the buildup of tau proteins inside brain nerve cells and the accumulation of beta-amyloid outside these cells has been unclear. Using mouse models, Johns Hopkins scientists have shed light on this relationship, which could pave the way to more effective therapies. Previous studies of early-onset Alzheimer’s have suggested the aggregation of beta-amyloid outside the cells is responsible for the clumping of tau proteins inside them, which causes brain cell degeneration and dementia. Instead, the new study shows that beta-amyloid buildup “is insufficient” to cause tau to “convert” from a normal state into an abnormal state in which it accumulates. Instead, it indirectly affects tau buildup by bringing about a “chain of chemical signaling events” that leads to its “conversion” into its clumping state. “For the first time, we think we understand that the accumulation of amyloid plaque alone can damage the brain, but that’s actually not sufficient to drive the loss of nerve cells or behavioral and cognitive changes,” Wong said in a statement. “What appears to be needed is a second insult--the conversion of tau--as well.” The team crossbred two groups of genetically modified mice to create a model that reflected more accurately the development of dementia in humans. The first group was engineered to accumulate beta-amyloid, while the second was engineered to accumulate tau protein in response to a tau fragment. They found in brain dissections that while beta-amyloid plaques weren’t able to directly “convert” tau to an abnormal state, their presence in the brain was still needed for tau to start clumping. This could be why some drugs intended to treat Alzheimer’s after the “conversion” of tau have failed, Wong said in the statement. “If you were to intervene in the time period before the conversion of tau, you might have a good chance of ameliorating the deficits, brain cell loss and ensuing consequence of the disease,” he said. And the results also suggest that a combination therapy to combat the buildup of beta-amyloid and the clumping of tau could be successful. - here's the statement

PD1

I do not have the time to review the information inundation that I get , so I picked 2 periodicals that reflect change from just today fiece Tech's submission from 3 am dealt with aMr. Sean Parker -former President of Napster, and facebook who is funding rewearch into DNA editing. Of the things edited PD1 receptor is high on the list Here is an article about the inhibitor of this receptor from Google Schoar Please take a look at it at your leisure and call for any questions

PD1

I do not have the time to review the information inundation that I get , so I picked 2 periodicals that reflect change from just today fiece Tech's submission from 3 am dealt with aMr. Sean Parker -former President of Napster, and facebook who is funding rewearch into DNA editing. Of the things edited PD1 receptor is high on the list Here is an article about the inhibitor of this receptor from Google Schoar Please take a look at it at your leisure and call for any questions