Search This Blog

Thursday, July 22, 2021

Illumina deal for Grail could hurt innovation, EU warns

 

U.S. life sciences company Illumina Inc's proposed acquisition of cancer test maker Grail Inc could curb innovation and competition, EU antitrust regulators warned on Thursday as they opened a full-scale investigation.

The European Commission's announcement confirmed a Reuters story last week.

Illumina announced the $8 billion cash-and-stock deal for startup Grail last September, buying out investors including Amazon founder Jeff Bezos, to regain control of a company it spun out five years ago.

Grail makes a non-invasive, early detection biopsy test to screen for many kinds of cancers using DNA sequencing.

The EU executive, which acts as the competition enforcer for the 27-country blc, said its preliminary investigation showed that Illumina could have an economic incentive to block Grail's cancer detection rivals.

"It is very important to preserve market conditions, allowing the best solutions to emerge for the tests to ultimately reach the market at affordable prices for the benefit of patients," Commission Executive Vice-President Margrethe Vestager said in a statement.

The EU watchdog will decide by Nov. 29 whether to clear or block the deal.

Sources have told Reuters that Illumina will need to offer hefty concessions to secure EU approval for the deal.

While seeking EU approval for the deal, Illumina is also challenging in court the EU decision to examine it even though it does not meet the revenue criteria.

https://www.marketscreener.com/news/latest/Illumina-deal-for-Grail-could-hurt-innovation-EU-warns--35924749/

INmune acquires LUMICKS Analyzer to accelerate NK cell platform for cancer treatments

 LUMICKS, a leading next generation life science tools company renowned for its innovative platforms for Dynamic Single-Molecule and Cell Avidity analysis, has installed its ground-breaking z-Movi® Cell Avidity Analyzer at INmune Bio (NASDAQ: INMB).

INmune Bio is a clinical stage biotechnology company developing new therapies that modulate the innate immune system to treat cancer and neurodegenerative diseases, such as Alzheimer's. Its Natural Killer Cell Priming Platform, INKmune® is a "pseudokine" which drives a patient's own natural killer (NK) cells to memory-type NK cells which kill persistent tumors that survive initial treatments.

INmune Bio is employing the z-Movi cell avidity analysis platform to demonstrate that the mechanism of action of the tumor-priming is the increase in NK cell:tumor cell avidity. Early data acquired by the z-Movi support their hypothesis that increased cell avidity enhances NK cell killing of tumor cells. This allows screening of batches of INKmune for potency and provides a potential biomarker of in vivo activity by measuring the tumor avidity of NK cells isolated from patients before and after INKmune treatment.

https://finance.yahoo.com/news/inmune-bio-acquires-lumicks-z-155300234.html

COVID Vaccine Janssen: EMA finds possible link to very rare cases of unusual blood clots

 

EMA confirms overall benefit-risk remains positive

At its meeting of 20 April 2021, EMA’s safety committee (PRAC) concluded that a warning about unusual blood clots with low blood platelets should be added to the product information for COVID-19 Vaccine Janssen. PRAC also concluded that these events should be listed as very rare side effects of the vaccine.

In reaching its conclusion, the Committee took into consideration all currently available evidence including eight reports from the United States of serious cases of unusual blood clots associated with low levels of blood platelets, one of which had a fatal outcome. As of 13 April 2021, over 7 million people had received Janssen’s vaccine in the United States.

All cases occurred in people under 60 years of age within three weeks after vaccination, the majority in women. Based on the currently available evidence, specific risk factors have not been confirmed.

PRAC noted that the blood clots occurred mostly at unusual sites such as in veins in the brain (cerebral venous sinus thrombosis, CVST) and the abdomen (splanchnic vein thrombosis) and in arteries, together with low levels of blood platelets and sometimes bleeding. The cases reviewed were very similar to the cases that occurred with the COVID-19 vaccine developed by AstraZeneca, Vaxzevria.

Healthcare professionals and people who will receive the vaccine should be aware of the possibility of very rare cases of blood clots combined with low levels of blood platelets occurring within three weeks of vaccination.

COVID-19 is associated with a risk of hospitalisation and death. The reported combination of blood clots and low blood platelets is very rare, and the overall benefits of COVID-19 Vaccine Janssen in preventing COVID-19 outweigh the risks of side effects.

EMA’s scientific assessment underpins the safe and effective use of COVID-19 vaccines. Use of the vaccine during vaccination campaigns at national level will take into account the pandemic situation and vaccine availability in individual Member States.

One plausible explanation for the combination of blood clots and low blood platelets is an immune response, leading to a condition similar to one seen sometimes in patients treated with heparin called heparin induced thrombocytopenia, HIT.

PRAC emphasises the importance of prompt specialist medical treatment. By recognising the signs of bloods clots and low blood platelets and treating them early, healthcare professionals can help those affected in their recovery and avoid complications. Thrombosis in combination with thrombocytopenia requires specialised clinical management. Healthcare professionals should consult applicable guidance and/or consult specialists (e.g., haematologists, specialists in coagulation) to diagnose and treat this condition.

As for all vaccines, EMA will continue to monitor the vaccine’s safety and effectiveness and provide the public with the latest information.

similar signal evaluation was recently finalised for another COVID-19 vaccine, Vaxzevria (previously COVID-19 Vaccine AstraZeneca).

Information for the public

  • Cases of unusual blood clots with low platelets have occurred in people who received Janssen’s COVID-19 vaccine in the United States.
  • The risk of having this side effect is very low, but people who will receive the vaccine should still be aware of symptoms so they can get prompt medical treatment to help recovery and avoid complications.
  • Individuals must seek urgent medical attention if they have any of the following symptoms in the three weeks after being vaccinated with COVID-19 Vaccine Janssen:
    • shortness of breath
    • chest pain
    • leg swelling
    • persistent abdominal (belly) pain
    • neurological symptoms, such as severe and persistent headaches or blurred vision
    • tiny blood spots under the skin beyond the site of the injection.
  • Speak to your healthcare professional or contact your relevant national health authorities if you have any questions about your vaccination.

Alexion: ICER Releases Draft Evidence Report on Therapies for Myasthenia Gravis

 Executive Summary 

Myasthenia Gravis (MG) is an autoimmune disease that affects the neuromuscular junction. The prevalence in the United States is estimated to be between 14 and 20 per 100,000 people1,2 and the annual incidence is approximately 2.2 per 100,000.3 The characteristic finding of MG is muscle weakness that worsens with repeated use (“fatigable weakness”).4 With progressive disease, treatment typically includes high-dose corticosteroids combined with or followed by “steroid-sparing” immunosuppressive drugs (most commonly azathioprine and mycophenolate mofetil [MMF]). The goal of therapy is to maintain the patient with minimal manifestations (MM) of disease (no symptoms or functional limitations from MG despite minimal weakness on examination) or better.5 Currently, about 20,000 patients with generalized MG are intolerant or have an inadequate response to conventional treatment options.6

 In this Report, ICER reviews eculizumab, a monoclonal antibody, and efgartigimod, an immunoglobulin fragment that targets the neonatal Fc receptor. Eculizumab received US Food and Drug Administration (FDA) approval in October 2017 for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-AChR antibody positive, 7 and an FDA decision on efgartigimod is expected on December 17, 2021.8 We identified one Phase III trial each for eculizumab (REGAIN) and efgartigimod (ADAPT) but found insufficient data to compare these drugs to maintenance intravenous immunoglobulin IVIG and rituximab (RTX). In the Phase III REGAIN trial, patients with anti-AChR antibody positive, treatmentresistant gMG who received eculizumab had significantly better improvement in the myasthenia gravis activities of daily living (MG-ADL) and quantitative myasthenia gravis (QMG) scores than those on placebo at four weeks and eight weeks (Table ES1), and the improvements were sustained at 26 weeks. In addition, at week 26, the proportion of patients with minimal symptom expression (MG-ADL score of 0 or 1) was much greater in the eculizumab group (21.4% vs. 1.7%, p=0.0007).9 In the open label extension through 130 weeks of follow up, the benefits were maintained, and may have increased compared with 26 weeks.10 There were no excess adverse events (AEs) in the trials, although more patients in the eculizumab group stopped treatment due to AEs, and it carries a black box warning for meningococcal infections. 

The Phase III ADAPT trial was conducted in gMG patients with or without anti-AChR-antibody; however, the primary outcome was in the subgroup of anti-AChR antibody positive patients. The proportion of patients with clinically meaningful improvement (≥2-point MG-ADL improvement sustained for ≥4 weeks) was much greater in the efgartigimod group compared to the placebo group. Anti-AChR antibody positive gMG patients who received efgartigimod did significantly better on MG-ADL and QMG than those who received placebo (Table ES1). However, the improvements were greater at four weeks than at eight weeks, reflecting the unusual dosing schedule in the trial.

Patients received their second treatment cycle only when they no longer had a clinically meaningful improvement on the MG-ADL. Thus, many patients were back near baseline at eight weeks. The anti-AChR antibody negative patients randomized to efgartigimod were only slightly more likely to respond based on the MG-ADL (68% vs. 63% in placebo group, p=NR). AEs did not appear to be more common with efgartigimod, but there are long term concerns about infections with lowering of IgG levels. 

One important area of uncertainty is that it is not clear if or when to stop either of the drugs in patients who are responding to them. For efgartigimod, the primary uncertainty is the appropriate dosing regimen. In the ADAPT trial, subsequent cycles were started once patients lost clinical benefits. It seems likely that in routine practice, patients and clinicians will not want to wait until the benefits have receded before starting another round of therapy. Also, despite their use in clinical practice, there is a lack of comparative efficacy data for both rituximab and IVIG used as maintenance therapy for gMG. Taking into consideration the above information on the benefits and AEs of eculizumab, we believe there is moderate certainty of a small or substantial net health benefit with high certainty of at least a small benefit for eculizumab added to conventional therapy (B+) in adults with gMG positive for anti-AChR antibodies “refractory” to conventional therapy. For efgartigimod, given the uncertainties about dosing and consistent long-term benefits of therapy, we concluded that there is moderate certainty of a comparable, small, or substantial net health benefit of efgartigimod added to conventional therapy with high certainty of at least comparable net health benefit (C++) in adults with gMG positive for anti-AChR antibodies. While there is evidence for efgartigimod in adults with gMG negative for anti-AChR antibodies, it is sparse and of uncertain clinical and statistical significance. Thus, we concluded that the evidence was insufficient (I) to distinguish the net health benefit of efgartigimod added to conventional therapy from conventional therapy alone in patients who test negative for anti-AChR antibodies. In addition, the evidence is insufficient (I) to distinguish the net health benefits of rituximab and IVIG from placebo, eculizumab, and efgartigimod. In economic modeling, we evaluated the cost-effectiveness of (1) eculizumab plus conventional therapy versus conventional therapy alone in patients with refractory anti-AChR antibody positive gMG as defined in the REGAIN trial and (2) efgartigimod plus conventional therapy versus  conventional therapy alone in the patients with gMG including those with or without anti-AChRantibody. 

The analyses were conducted over a two-year time horizon, taking a health system perspective. Based on an annual cost of $470,200, the incremental cost/QALY and incremental cost/evLYG for eculizumab were estimated to be $3,746,000. For efgartigimod, using a placeholder price of $286,100, the incremental cost/QALY and incremental cost/evLYG were estimated to be $1,426,000. The model was sensitive to several inputs, including the utility values assigned to improved and unimproved MG and the proportion of patients achieving at least a 3-point reduction in the QMG for efgartigimod or its comparator, or eculizumab and its comparator. However, despite the large impact of changing these inputs on the results, the incremental cost-effectiveness ratio was never less than $2.5 million per QALY gained for eculizumab and $1.14 million per QALY gained for efgartigimod. In addition, the results of the probabilistic sensitivity analysis and scenario analyses had similar cost/QALY estimates. There are other potential benefits and important contextual considerations not fully captured in the economic model. For example, MG is a serious, lifelong disease with life-threatening manifestations, and most patients do not achieve treatment goals with conventional therapy. Additionally, there is potential to improve childbearing and career opportunities for women who are often diagnosed early in their lives. This is particularly relevant for Black women who typically present at younger ages and may have a more severe disease course than other patient groups. In conclusion, both eculizumab and efgartigimod significantly improve function and quality of life for patients with gMG. However, at the current price for eculizumab the estimated costeffectiveness is well above typical thresholds; the cost-effectiveness of efgartigimod will depend on its actual price.

https://icer.org/wp-content/uploads/2021/03/ICER_Myasthenia-Gravis_Draft-Evidence-Report_072221.pdf

Humanigen S. Korea partner gets safety OK for Phase 1 covid trial

 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), today announced its development and commercialization partners for South Korea and the Philippines, Telcon RF Pharmaceutical, Inc. ("Telcon") and KPM Tech Co., Ltd. ("KPM Tech"), have received approval from South Korea’s MFDS (the South Korean equivalent of the U.S. FDA) to conduct a Phase 1 clinical study of lenzilumab, which may support potential use in the treatment of hospitalized COVID-19 patients.

The study, to be conducted by Telcon and KPM Tech at the Seoul National University Hospital, is a randomized, placebo-controlled, double-blind, single-dose, dose escalation of lenzilumab in 20 healthy Korean adults. The primary endpoints of the study are the safety, tolerability, and pharmacokinetics of lenzilumab. If FDA grants emergency use authorization for lenzilumab in the treatment of hospitalized COVID-19 patients in the United States, Telcon and KPM Tech plan to apply to MFDS for conditional approval for importation of lenzilumab for use in Korea. Support for conditional approval would be based on data from this phase 1 study and the existing data from Humanigen’s Phase 3 LIVE-AIR study. Additional clinical trials are not expected to be necessary in this situation.

https://finance.yahoo.com/news/humanigen-partner-south-korea-receives-135900702.html

Answer to medical misinformation on social media might be more information

 When the surgeon general of the United States speaks, people tend to listen. So Vivek Murthy’s recent 22-page report proclaiming that the spread of misinformation through social media has become an “urgent threat to public health,” and that more needs to be done to combat the issue, is bound to get some attention.

He has a point: Social media is at the heart of misinformation.

But social media also has the power to drive public health discussion, a point that runs through the report but is never highlighted. That’s why we believe that solving the misinformation epidemic will require that medical trainees like us along with members of the broader public health community not only keep a sharp eye out for misinformation campaigns but that also actively engage friends, families, and loved ones with evidenced-based conversations on these same platforms.

As physicians in training and social media users, we have seen firsthand evidence of this positive side of social media. On Twitter, for example, adding the hashtag #medtwitter to a tweet makes it visible to countless individuals interested in the latest updates in medicine. Social media also offers opportunities for various stakeholders such as politicians, venture capitalists, academics, and others to share their insights and find solutions for the most challenging issues of our time.

As the U.S. engages in a campaign to increase vaccination rates and combat the rising outbreaks of the Delta variant, much of the conversation has centered on issues related to vaccine distribution, future health care transformations, and worsening health inequities. Moving beyond the pandemic, we believe this kind of cross-talk should be leveraged to create networks of professionals that share credible health information and ultimately chart a pathway for improved long-term public health.

Social media platforms serve as great ways for stakeholders to communicate primarily because these platforms have millions of users across multiple areas of expertise and are already optimized to facilitate interaction about shared interests. Since the emergence of the coronavirus pandemic in 2020, the hashtag #Covid19 on Twitter has created a feed that doctors, public health officials, politicians, economists, and others have used to share their work.

The general public also benefits because this joint feed facilitates cross-disciplinary virtual panels that have helped educate and disseminate credible updates about the pandemic. Even though Covid-19 is biological in nature, addressing its societal implications require collaborations to devise innovative solutions, and social media has facilitated that cross-talk faster than ever before. What would have taken multiple phone calls and emails can now take a single retweet, message, or comment.

For example, one of us (P.J.) recently messaged multiple physicians over Twitter who were sharing novel insights into the pandemic. Upon connecting, the physicians expressed interest in creating a joint feed to share the most up-to-date news in health. What emerged was a Twitter account titled: “Health News Around the World,” which now is used by multiple physicians to share the most recent up-to-date health news occurring on a daily basis.

That is just one of the ways we have leveraged the power of retweets to share stories of what moving to a Covid-19 free world would look like. In fact, we recently took part in the #thisisourshot movement to help foster collaborations with national student medical groups such as the Student National Medical Association, the Latino Medical Student Association, and the American Medical Women’s Association to highlight issues of vaccine hesitancy in different communities. More importantly the This Is Our Shot movement also aims to support the broader efforts of more than 25,000 health care workers who are working to get our population out of this pandemic.

One of the most inspiring aspects of this campaign has been the opportunity to use social media for people to share stories about the communities they love. Ultimately, this campaign has promoted vaccinations as individuals not only feel heard but are getting information from sources they relate to.

Another example of social media facilitating cross-disciplinary collaboration comes from the release of Clubhouse, an audio-based social media app that allows people across the globe to join virtual rooms and talk about topics of interest, including Covid-19, vaccine distribution, vaccine hesitancy, and more. Since its release in April 2020, the app has skyrocketed in popularity and now has more than 10 million weekly active users.

Clubhouse is much like Twitter, but its competitive advantage comes from the fact that Clubhouse allows individuals to talk to one another through an audio interface. As medical students, we were interested in using Clubhouse to battle misinformation about the Covid-19 pandemic. We invited faculty members at Yale, where we are both students, who were actively researching Covid-19 and created multiple rooms in the All Things Covid club, which was started by a group of physicians to help answer questions about the evolving Covid-19 pandemic. These rooms attracted thousands of listeners and helped fight misinformation through voice-to-voice interactions that would have otherwise never occurred. Today, this club has nearly 45,000 members and continues to hold weekly town hall meetings, each of which promotes cross-talk across people of all backgrounds and helps set the stage for innovative solutions.

Instead of reining in the use of social media, we believe that the medical community should go on the offensive and fight misinformation on social media domains by coordinating networks of reputable individuals who can serve as sources of credible information on these domains. This will allow students, attending physicians, epidemiologists, health care entrepreneurs, and many others to engage with family and friends within and outside of medicine to help spread truthful information in the same way leaders with large platforms can engage their spheres of influence. Most importantly, social media will allow anyone in medicine and health care more broadly to promote inclusive discussions that get at the heart of individual concerns.

Whether it is by hosting interactive Clubhouse discussions that allow individuals to openly voice their concerns or creating trending movements like #thisisourshot, social media has the potential to engage and resonate with local communities. One of us (V.A.) recently had an in-person discussion with a staff member at the VA Ann Arbor Healthcare System who was reluctant to get vaccinated because of concerns that extremely rare side effects, like Guillain-Barré syndrome that might be associated with the Johnson & Johnson vaccine, would be a greater danger than the virus. Upon further discussion, these concerns appeared to arise from online rumors. These concerns stemmed from what the staff member had read online. Although the conversation ended with the staff member feeling confident that he would not get vaccinated, given that he has already had Covid-19 and felt that Covid-19 was being sensationalized in media, it offered a glimpse into the need for the medical community to more actively engage in the social media arena.

Well-meaning discussions like that one that connect trainees, the academics who train them, researchers, and members of the public is what intentional social media engagement can foster. For doctors and doctors-in-training like us, the moment has always been right to prioritize science and public health. But it’s important that this be done by first taking into account the diversity of perspectives, experiences, and cultures that exist within the medical community itself and the broader society. Only by intentionally engaging in cross-disciplinary conversation can the medical community create the durable coalitions and political willpower necessary to improve public health in the face of current and future pandemics.

Victor Agbafe is a candidate for dual M.D. and J.D. degrees at the University of Michigan Medical School and Yale Law School. Prerak Juthani is a candidate for dual M.D. and M.B.A. degrees at Yale School of Medicine and Yale School of Management.

https://www.statnews.com/2021/07/22/answer-medical-misinformation-social-media-more-information/

ISTH 2021 – Biomarin’s valrox fades again

 Biomarin’s haemophilia A gene therapy valoctocogene roxaparvovec (valrox) was already under scrutiny over fading factor VIII levels. An update yesterday from its phase 1/2 trial, presented at the ISTH meeting, will have done nothing to allay those fears. At five years FVIII levels among seven patients treated with the highest dose, 6x1013vg/kg, had dropped to a median of just 8%. Biomarin will no doubt point to the fact that among six of these patients the mean annualised bleeding rate fell by 95% over this period and that, even at five years, 86% of patients had no bleeds. But it is still unclear how long valrox’s effect might last – not ideal for a supposedly once-and-done therapy that cannot be redosed. Valrox is already in a pivotal trial, Gener8-1, and an early look also suggested fading FVIII levels at two years. Two-year results on all participants in Gener8-1 are expected in early 2022. Biomarin might then be able finally to refile valrox, which was rejected by the FDA last year. However, even if it is approved, patients might choose to hang on for something better. Evaluate Pharma sellside consensus puts valrox’s 2026 sales at $695m, down from $1.8bn in April 2020.

FVIII levels with 6e13 vg/kg dose of valrox over time: phase 1/2 results (NCT02576795)
YearMeanMedian
164.3%60.3%
236.4%26.2%
332.7%19.9%
424.2%16.4%
511.6%8.2%
Results all with chromogenic substrate assay. Source: company releases.

https://www.evaluate.com/vantage/articles/news/snippets/isth-2021-biomarins-valrox-fades-again