Grifols presents additional encouraging Alzheimer’s trial results at AAIC

New data shows positive impact of AMBAR treatment on efficacy endpoints combining cognition and function in all patients treated
The results are in line with the ones presented in CTAD in Barcelona and AD/PD in Lisbon

The Grifols Clinical Research team, led by Dr. Antonio Páez, today presented additional results of its AMBAR (Alzheimer Management by Albumin Replacement) clinical trial for the treatment of Alzheimer’s at the Alzheimer’s Association International Conference (AAIC) 2019 in Los Angeles (USA).

The first results were presented at the 11th Clinical Trials on Alzheimer’s Disease (CTAD) Conference in Barcelona (Spain) in October 2018 and at the 14th International Congress on Alzheimer’s and Parkinson’s (AD/PD) in Lisbon (Portugal) in March 2019.

These results showed a statistically significant reduction of 61% in disease progression in both primary efficacy endpoints, ADAS-Cog (Alzheimer’s Disease Assessment Scale – cognitive) and ADCS-ADL (Alzheimer’s Disease Cooperative Study – Activities of Daily Living) scales, in the cohort of moderate patients. Regarding specific cognitive aspects, the AMBAR treatment showed positive effects on memory in the moderate patients, and on language and processing speed in patients with the disease in a mild stage.

The additional results presented today at the AAIC point in the same direction in all treated groups across the different relevant endpoints that combine assessments of cognitive status and daily functioning: Clinical Dementia Rating – Sum of Boxes (CDR-Sb) and Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC).

In particular, the CDR-Sb scale — which assesses memory, orientation, judgment, community affairs, home and hobbies, and personal care — shows a statistically significant 71% less decline with respect to placebo in patients treated as a whole. This significance remains when analyzing the three study treatment arms separately, with less decline at 14 months that ranged 65-71%.

Analysis of mild and moderate cohorts displays a statistically significant less decline of 53% in moderate patients and a statistically significant improvement in mild ones, suggesting that for this endpoint the effect of the treatment might be higher in earlier phases of the disease.

For the ADCS-CGIC scale, which assesses several domains of cognition, daily functioning and behavior from both the patient and the caregiver perspective, the results are in line with those of the CDR-Sb scale: a statistically highly significant stabilization is observed in all treated patients with respect to placebo. This effect remains in all three treatment arms when analyzed separately.

As in the case of CDR-Sb scale, the positive and statistically significant effect is also observed for ADCS-CGIC in the moderate-patient cohort. Moreover, there’s a remarkable statistically significant improvement in the mild-patient cohort when compared with placebo at 14 months of treatment. All these effects are replicated when the three treatment arms are assessed against placebo.

At AAIC, Dr. Páez also shared that the plasma amyloid-beta saw-tooth mobilization pattern observed in earlier clinical trials is similar for both conventional and low-volume plasmapheresis performed in the AMBAR trial. This, reinforces the investigational use of smaller volumes of plasma protein replacement therapies.

These encouraging results strengthen Grifols’ commitment in the fight against Alzheimer’s disease. A further update with the complete clinical, biomarker and neuroimaging results will be presented at the CTAD in San Diego (USA) in December 2019.

https://www.biospace.com/article/releases/grifols-presents-additional-encouraging-alzheimer-s-trial-results-at-aaic/

VTv Therapeutics to present at Alzheimer's conference

VTv Therapeutics (NASDAQ:VTVT) has risen 8.8% postmarket after it says it will present at this week's Alzheimer's Association International Conference.

The oral presentation will cover data from its phase 3 STEADFAST study and the preceding phase 2B study of azeliragon to "further support the biological hypothesis for the potential beneficial effects of azeliragon on the ADAS-cog and CDR-sb in patients with mild Alzheimer’s disease and type 2 diabetes."

Azeliragon is an orally active small-molecule antagonist of the receptor for advanced glycation endproducts (RAGE). https://seekingalpha.com/news/3477913-vtv-therapeutics-present-alzheimers-conference-shares-plus-8_8-percent

FDA accepts file and accelerates review of Novartis sickle cell disease med

• FDA grants crizanlizumab Priority Review based on Phase II data showing prevention of vaso-occlusive crises (VOCs) in patients with sickle cell disease, shortening FDA review to six months from standard ten months
• Vaso-occlusive crises (also called sickle cell pain crises) are unpredictable and extremely painful events that can lead to serious life-threatening complications and death[1]

Novartis today announced the US Food and Drug Administration (FDA) accepted the company’s Biologics License Application (BLA) and has granted Priority Review for its investigational sickle cell medicine crizanlizumab (SEG101). If FDA-approved, crizanlizumab is expected to represent the first monoclonal antibody targeting the P-selectin mediated multi-cellular adhesion in sickle cell disease.

Novartis submitted the application for crizanlizumab for the prevention of vaso-occlusive crises (VOCs) in patients with sickle cell disease (SCD) and was granted Breakthrough Therapy designation in December 2018. VOCs are unpredictable and extremely painful events that can lead to serious acute and chronic life-threatening complications and death. VOCs also lead to significant health care utilization. They are the most common cause of emergency room visits and hospital admissions for SCD patients, with total medical costs exceeding $1.1 billion annually in the United States[2].

Priority Review is granted to therapies that the FDA determines have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The designation is intended to shorten the FDA review period to six months from the standard ten months.

https://www.marketscreener.com/NOVARTIS-9364983/news/Novartis-FDA-accepts-file-and-accelerates-review-of-Novartis-sickle-cell-disease-medicine-crizanli-28908527/

J&J Okla. trial winds up closing arguments

The state of Oklahoma and Johnson & Johnson agree on one thing: Oklahoma has an opioid crisis.

Where they strongly disagree is who created the problem and what should be done to fix it.

Attorneys for the two sides made that clear Monday during closing arguments in a case where the opioid maker has been accused of helping cause the crisis through false and deceptive marketing that understated the addictive and overdose risks of opioid painkillers while overstating there therapeutic benefits.

“What is truly unprecedented here is the conduct of these defendants in embarking on a cunning, cynical and deceitful scheme to create and feed the need for opioids,” Attorney General Mike Hunter said. “Why did they do this? … Greed.”

Hunter said the company’s actions included engineering a mutant poppy to amplify the need for opioids, and overstating the effectiveness and minimizing the risks of the drugs in marketing materials. Those actions also included oversupplying “these addictive drugs that have devastated Oklahoma communities and wrecked countless Oklahomafamilies,” he said.

“The only question is whether the Oklahoma taxpayer or the ‘kingpin’ of it all should be required to bear the cost,” Hunter said.

Speaking on behalf of Johnson & Johnson, Oklahoma City attorney Larry Ottaway said the situation is complicated. He argued that it would be wrong to blame Johnson & Johnson for the crisis.

Ottaway pointed to testimony by Oklahoma doctors who said they were keenly aware of the risks of opioids but continued to prescribe them because untreated pain also carries risks, including diminished quality of life, loss of function, depression and even suicide.

Those risks, including the risks of addiction and death, are clearly pointed out in federal Food and Drug Administration labeling instructions that are required to accompany every prescription, he noted.

Ottaway argued the solution to the problem would be to let Oklahoma doctors continue to make prescribing decisions.

“I trust them,” Ottaway said. “We trust them with our lives every day.”

The state wants Cleveland County District Judge Thad Balkman to declare that the actions of Johnson & Johnson and its subsidiaries created a public nuisance and to order them to pay more than $17.5 billion to abate the problem.

Judge Balkman indicated it will likely be the end of August or early September before he issues a verdict in the non-jury trial. Balkman said he will give attorneys until July 31 to file proposed findings of fact and conclusions of law in the case and then will take about another month before issuing his decision.

Oklahoma experienced more than 6,100 prescription opioid-related deaths from 2000-2017.

Attorneys used their closing arguments Monday to highlight what they consider to be key testimony in a trial that lasted more than a month and a half.

State attorneys once again ripped Johnson & Johnson for using sales representatives, self-funded studies, key opinion leaders and speakers at company-funded continuing education events to promote the message to doctors that opioids have a low addiction rate if prescribed properly to appropriate patients who are carefully monitored.

Using a game show type format that he called “Who wants to be a pain franchise billionaire?” state’s attorney Brad Beckworth ridiculed Johnson & Johnson for calling witnesses who cited reports that claimed opioids have a low addiction rate. Some reports claimed the addiction rate was a fraction of 1%.

Beckworth noted that one of the drug company’s expert witnesses, before he came to court, had made a presentation in which he stated the addiction rate was 25%. And another drug company witness, a doctor, testified the addiction rate was 100 percent if a patient stayed on the drug long enough, Beckworth said.

Johnson & Johnson’s corporate representative testified during the trial that the actual rate of opioid addiction is unknown.

Beckworth criticized Johnson & Johnson for having its sales representatives target high prescribers of opioids for additional sales calls and for tying their sales representatives’ pay to the amount of additional prescriptions that doctors wrote.

“When it comes to pushing narcotics, you should never pay people, incentivize them, to get more drugs prescribed,” Beckworth said. “That’s just not right.”

Ottaway, the attorney for Johnson & Johnson, used part of his closing argument to remind the judge that the company’s branded products had an extremely small portion of the market share in Oklahoma and weren’t among the most widely abused, because the company had taken steps to make them as tamper proof as possible.

State attorneys questioned whether Johnson & Johnson’s market share was relevant, reminding the judge of testimony that at the height of the opioid crisis, a Johnson & Johnson subsidiary was providing numerous other opioid manufacturers with the active pharmaceutical ingredient for their opioids.

Throughout the trial, the state’s attorneys referred to Johnson & Johnson as a “kingpin” in the opioid crisis, citing the role of the company’s then-subsidiary Noramco in supplying active ingredients to other opioid manufacturers.

“Johnson & Johnson knew opioid drugs are addictive and cause harm” but chose to market them for “everyday pain,” Beckworth said. “When you oversupply, people will die.”

Johnson & Johnson’s attorney pointed to testimony that the amounts of active ingredients Noramco was allowed to manufacture and that other companies were allowed to purchase were tightly regulated by the federal Drug Enforcement Administration. Johnson & Johnson divested itself of Noramco in 2016.

The Oklahoma opioid trial has been closely watched nationally because it is the first of hundreds of similar lawsuits filed nationally that has actually made it to trial. More than 1,700 of the other lawsuits have been consolidated in a major federal court action pending in Ohio.

Oklahoma’s lawsuit originally named two other groups of pharmaceutical companies as additional defendants, but they were dropped from the lawsuit after they approved settlement agreements with the state. A group headed by Purdue Pharma agreed to pay $270 million, while a group headed by Teva Pharmaceuticals USA Inc., agreed to pay $85 million.

https://www.marketscreener.com/JOHNSON-JOHNSON-4832/news/Johnson-Johnson-Attorneys-make-closing-arguments-in-state-case-against-opioid-manufacturer-28908254/

Boehringer buys up cancer vaccine player, eyes oncology combo strategy

German pharma Boehringer Ingelheim is putting a few hundred million euros on the table to snap up Swiss cancer biotech Amal Therapeutics.

BI gets access to Amal’s so-called KISIMA platform, which uses peptide/protein-based vaccination tech aimed at treating lung and gastrointestinal cancers.

The private biotech’s lead vaccine ATP128 is currently developed for late-stage colorectal cancer and is slated to begin first-in-human trials later this month.

Boehringer explained in a statement that it “plans to develop new therapies by combining assets from its cancer immunology portfolio with Amal’s proprietary KISIMA immunization platform.”

Details are a little thin, with no upfront amount made public, but all in all the buyout could cost BI €325 million, including an upfront payment as well as biobucks payouts, plus up to €100 million “if certain commercial milestones are hit,” the company added.

Amal will maintain its home on the campus of the University of Geneva in Switzerland, working as a subsidiary within Boehringer. The pair already has deep ties, and last November the German cancer company helped power Amal to a €21.2 million ($24 million) series B round.

Amal spun out of the University of Geneva in 2012 to advance technology with the potential to address limitations that held back earlier generations of cancer vaccines. The tech is based on a chimeric protein made up of three functional parts, including a cell-penetrating peptide the biotech thinks will promote the efficient cross presentation of epitopes to cytotoxic T cells.

“Acquiring Amal is part of Boehringer Ingelheim’s long-term strategy to enhance our existing position as an innovator of novel cancer therapies, including immuno-oncology treatments, which leverage cutting-edge scientific discoveries and their applications,” said Michel Pairet, a member of Boehringer’s board.

“We want to pioneer new paradigms of biology-based care for cancer patients, and the technologies and expertise developed at Amal are critical to our efforts.”

 “I am extremely proud of the hard work of Amal’s entire team, which is validated by this acquisition, and very excited to further develop the KISIMA technology platform within Boehringer Ingelheim,” said Madiha Derouazi, Ph.D., founder and CEO of Amal.

“Our new relationship with Boehringer Ingelheim will enable us to realize the full potential of our KISIMA platform to fight solid cancers while preserving Amal’s approach to biotechnology research and our scientific and academic networks. Moreover, sharing resources and capabilities in clinical development will greatly help us to move ATP128 and other assets forward.”

This builds on BI’s 2018 buyout of Vira Therapeutics and the in-licensing of OSE Immunotherapeutics’ SIRP-alpha targeting antibody as the company looks to expand beyond its approved lung cancer therapy afatinib and into immuno-oncology.

https://www.fiercebiotech.com/biotech/boehringer-buys-up-cancer-vaccine-player-eyeing-oncology-combo-strategy

Johnson & Johnson Q2 2019 Earnings Preview

Johnson & Johnson (NYSE:JNJ) is scheduled to announce Q2 earnings results on Tuesday, July 16th, before market open.

The consensus EPS Estimate is $2.44 (+16.2% Y/Y) and the consensus Revenue Estimate is $20.39B (-2.1% Y/Y).

Over the last 2 years, jnj has beaten EPS estimates 100% of the time and has beaten revenue estimates 88% of the time.

Over the last 3 months, EPS estimates have seen 12 upward revisions and 3 downward. Revenue estimates have seen 2 upward revisions and 9 downward.

https://seekingalpha.com/news/3477728-johnson-and-johnson-q2-2019-earnings-preview

Intuitive Surgical acquires Schölly Fiberoptic’s robotic endoscope business

Intuitive (Nasdaq: ISRG), the pioneer and a global leader in robotic-assisted, minimally invasive surgery and manufacturer of da Vinci surgical systems, today announced the acquisition of Schölly Fiberoptic’s robotic endoscope business.

Intuitive is acquiring the robotic endoscope portion of Schölly Fiberoptic’s business. This acquisition will integrate Schölly’s robotic endoscope manufacturing line, and two Schölly sites into Intuitive operations:  the robotic-related manufacturing line from Denzlingen, Germany; the manufacturing site in Biebertal, Germany; and the repair site in Worcester, Mass., USA. Intuitive will welcome and integrate into its team approximately 200 staff from these three sites over the next 18 months.

“Schölly has been an important and valued vendor for Intuitive since the very early days of the company,” said Brian Miller, Intuitive senior vice president for systems and vision.

“Leading visualization has been a core pillar of our company and we expect it to continue to be important going forward,” said Miller. “It makes sense to bring the teams together for both organizations.”

Schölly Fiberoptic is a leading player in the field of visualization systems for minimally invasive diagnostic and surgical applications, headquartered in Germany—and one of Intuitive’s strategic suppliers. The companies have worked together for more than 20 years, designing and manufacturing several generations of imaging systems for Intuitive’s da Vinci surgical systems.

https://www.marketscreener.com/INTUITIVE-SURGICAL-9740/news/Intuitive-Surgical-acquires-Scholly-Fiberoptic-s-robotic-endoscope-business-28906822/