Lilly CEO Expresses Confidence for the Company in the New Year

Days after acquiring Loxo Oncology, Eli Lilly Chief Executive Officer David Ricks outlined projections for the new year and said that he, and other executive leaders, feel confident about the position that the company now finds itself.

During a fireside chat at the annual J.P. Morgan Healthcare Conference in San Francisco, Ricks said that about 45 percent of the coming year’s revenue will be generated by medications launched in 2015. Those drugs include Trulicity, Taltz and Verzenio, Ricks said. Additionally, he said Indianapolis-based Eli Lilly anticipates the launch of two new molecular entities this year — nasal glucagons, a rescue medicine for hyperglycemia, as well as Lasmiditan a rescue medicine for migraine headaches.

In addition to the drug launches, Ricks said the company will invest an additional $400 million in R&D in 2019. The investments will be made, in part, to support three important Phase III programs, he said, according to a transcript. The late-stage programs are Tirzepatide, the dual GIP/GLP agonist for diabetes and other indications, Mirikizumab in both ulcerative colitis and psoriasis. That one could also have applications for Crohn’s, he noted. The third program Ricks pointed to is Pegilodecakin, which is being studied in both lung cancer and pancreatic cancer.

“As we step back, I think we’re feeling very good about where the company is for several reasons. First, we’ve got very broad base of growth drivers, potentially eight blockbuster of products that have already launched in the last five years and we have potentially 10 more launches in the next five. We’re optimistic about our ability to grow the company based on volume across a broad range of therapy areas and a broad set of brands,” Ricks said, according to a transcript of the fireside chat.

Ricks added that the company has a strong pipeline that is backed by a research team “working on the right targets.” He said the company is focused on five therapy areas and is increasing its business development to support those areas. Part of that work includes some of the assets acquired in the Loxo deal, which was announced this week. He pointed to Loxo’s recently approved TRK inhibitor, which will be launching soon. Also, Ricks noted that Loxo has a developmental pipeline that includes LOXO-195, which “seeks to overcome what would be the predicted resistance to buy TRKV.” But, Ricks noted that the asset Eli Lilly was most keen for was the RET inhibitor LOXO-292. He said the medication addresses RET mutations the same way TRKV does for TRK mutations.

“Finally, they’ve got a little engine of scientists that continue to work on these precision medicine strategies and we’d be excited to have them keep doing it,” Ricks said of the Loxo team.

The Loxo deal reaffirms Eli Lilly’s dedication to one of its core strengths in oncology. Ricks said this will likely remain an area where the company expects to be “busy.”

Ricks pointed to a number of other programs that will likely be strong drivers for the company, including immunology and diabetes.

“We have a good position in all the markets we play in and as we look toward the next wave of growth driven by pain and potentially other neuroscience assets, we find the company in a very good place,” he said.

As the fireside chat came to a close, Ricks addressed some of the challenges faced with out-of-pocket expenses for medications. He criticized the payment structures set in place by insurance companies that force many patients to pay a higher cost. He said there could be several measures to address this, including sharing rebates at the point of sale for pharmaceuticals, something he said already occurs for many medical procedures. Ricks also pointed to potential platforms from insurance companies that would allow consumers to select low-rebate or high-rebate medications. Lastly, Ricks said that there is a potential rule change being developed by the White House that could change the rebate model completely. One pricing measure the company is taking to is to include a link to a website, lillypricinginfo.com, in all its advertisements that provides information about the costs of the medication.

https://www.biospace.com/article/eli-lilly-ceo-expresses-confidence-for-the-company-in-the-new-year/

Schizophrenia linked with abnormal immune response to Epstein-Barr virus

New research from Johns Hopkins Medicine and Sheppard Pratt Health System shows that people in the study with schizophrenia also have higher levels of antibodies against the Epstein-Barr virus (EBV), a herpes virus that causes infectious mononucleosis, so-called mono.

Researchers proposed two explanations for the association of heightened immune responses in patients with schizophreniaand EBV infection: schizophrenia might alter the immune systems of these patients and make them more susceptible to EBV, or EBV infection might increase the risk of schizophrenia.

The article was published online Nov. 20 in Schizophrenia Bulletin.

“We are interested in the role of infectious agents such as Epstein-Barr virus in schizophrenia and other serious psychiatric disorders, so we did this study to look at the associations,” said Robert Yolken, M.D., the Theodore and Vada Stanley Distinguished Professor of Neurovirology in pediatrics at Johns Hopkins Children’s Center and senior author of the study. Yolken cautioned that the study wasn’t designed to determine cause and effect.

Schizophrenia is a mental disorder where patients have distorted thinking, perception, emotions, language, sense of self and behavior. According to the World Health Organization, schizophrenia affects more than 21 million people worldwide.

While schizophrenia has some genetic associations, genes that have been found to date explain only a portion of the disease risk. Environmental exposures, including to some infectious agents, have also been identified in previous studies as increasing the risk for schizophrenia.

EBV initially causes fever and swollen lymph nodes, and is commonly transmitted through oral contact such as kissing. In severe cases, it can spread to the central nervous system and cause persistent infection. Researchers wanted to see the relationship between this EBV infection and schizophrenia.

The researchers conducted a study among 743 people—432 with a schizophrenia diagnosis and 311 without a history of a psychiatric disorder to serve as a control group. Around 55 percent of the participants were men.

The researchers first measured levels of antibodies against components of EBV by comparing antibody levels in healthy people with those of people who have schizophrenia. They looked at the odds of having these antibodies in the 50th, 75th and 90th percentiles and found that people with schizophrenia were 1.7 to 2.3 times more likely to have increased levels of some EBV antibodies compared with people without schizophrenia.

Then they measured the antibodies to other related viruses such as varicella/chicken pox or herpes simplex type 1/cold sore virus, and didn’t find an increase of antibodies against these viruses in people with schizophrenia. These findings suggest that only EBV was associated with increased risk of schizophrenia.

After that, the researchers sequenced a portion of the participants’ DNA to determine their genetic risk for schizophrenia. Results from the analysis showed that people who had both evidence of increased genetic risk for schizophrenia and increased antibody levels to EBV had a more than eight times higher chance of being in the schizophrenia group as compared with controls. Approximately 10 percent of the individuals with schizophrenia had increased levels of both antibodies and genetic risk as compared with slightly more than 1 percent of the controls.

“We found that individuals with schizophrenia had an unusual response to Epstein-Barr virus,” said Yolken. “This indicated that the prevention and treatment of Epstein-Barr virus might represent an approach for the prevention and treatment of serious psychiatric disorders such as schizophrenia.”

Currently, there are no treatments available for EBV approved by the Food and Drug Administration, but a number of compounds that may prevent or treat replication of the virus are under investigation. The researchers considered the development of these approaches a high priority so that people with schizophrenia or other disorders associated with susceptibility to EBV could use them. In the meantime, researchers recommend preventing EBV transmission through good hygienic practices such as hand-washing and avoiding oral contact, such as kissing, with infected people.

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More information: Faith Dickerson et al. Schizophrenia is Associated With an Aberrant Immune Response to Epstein–Barr Virus, Schizophrenia Bulletin (2018). DOI: 10.1093/schbul/sby164

https://medicalxpress.com/news/2019-01-schizophrenia-linked-abnormal-immune-response.html

Cancer Immunotherapy ‘Explosion’ to Continue in 2019

As 2019 progresses, cancer immunotherapy with checkpoint inhibitors will continue its evolution with multiple combination strategies that “will greatly improve responses,” a leading authority in the field predicted.

Two strategies will lead the way: combinations of different types of checkpoint inhibitors and combinations pairing a checkpoint inhibitor with chemotherapy, radiation therapy, and molecularly targeted agents. Combination therapy will build on the transformative foundation that immunotherapy established over the past few years in oncology.

“The field of immunotherapy is exploding,” 2018 Nobel Laureate James P. Allison, PhD said in Cancer Research Catalyst, the official blog of the American Association for Cancer Research (AACR). “For the first time, we have several potentially curative treatments for cancer, with some patients remaining cancer-free a decade or more after treatment.”

Development of checkpoint inhibitor-based combinations has to proceed in an evidence-based manner, added Allison, of the MD Anderson Cancer Center in Houston. That requires careful evaluation of tissue samples from cancer patients to guide drug selection and choose the right drugs, given at the right time, to optimize effectiveness.

“That’s going to be the biggest thing this year,” said Allison.

Allison was one of three cancer scientists who contributed to the blog. AACR president-elect Elaine Mardis, PhD, of Nationwide Children’s Hospital in Columbus, Ohio, and Brian Rivers, PhD, of Morehouse School of Medicine in Atlanta, also offered predictions for precision medicine and for cancer prevention and health disparities, respectively.

Currently, about a third of cancers respond to immune checkpoint inhibitors. Additionally, many patients who initially respond to the agents eventually develop resistance. Another area of emphasis in cancer immunotherapy will focus on strategies to overcome resistance.

Some patients have innate resistance. Combining a checkpoint inhibitor with chemotherapy, radiation therapy, or targeted therapy may overcome that type of resistance, said Allison. In other patients, resistance occurs as a result of acquired defects that lead to loss of response to lytic events or loss of antigen presentation mechanisms. CD4-targeted agents, particularly vaccines, may be effective in that setting.

Refinements in chimeric antigen receptor (CAR) T-cell therapy could lead to more effective treatment in 2019, Allison continued. Many laboratories already are evaluating methods to eliminate genes that inhibit T-cells or to introduce genes that code for specific cytokines or chemokine receptors. More research involving CAR T-cell therapy for solid tumors will come to the forefront, although hematologic malignancies will remain the principal focus.

Precision Medicine

Advances emerging from large-scale genomics-based studies of tumors will continue to drive developments in precision medicine, said Mardis. Much work remains to unravel the therapeutic implications of certain germline defects, such as the BRCA alterations that led to use of PARP inhibitors and the observation that high microsatellite instability may be a marker for sensitivity to immune checkpoint inhibitors.

“The biggest challenge of next-generation sequencing approaches that identify cancer genomic variants is that much of what we identify cannot be interpreted in terms of impact on function,” said Mardis, citing BRCA variants of uncertain significance (VUS) as an example. “The challenge created by this situation today can potentially be addressed using newer genome editing technologies for high-throughput functional studies that characterize VUS in a medical context.”

The coming year also should yield more systematic studies of liquid biopsy-guided treatment monitoring for drug resistance. Mardis said she also expects 2019 to be a big year for advances in the use of artificial intelligence in “understanding cancer as a system.” Additionally, the recent trend toward more emphasis on “the hardest targets” will continue, as basic and clinical scientists seek more effective treatment for some of the most difficult-to-treat cancers, such as glioblastoma multiforme and pancreatic cancer.

Prevention and Disparities

Rivers predicted an increased emphasis on “implementation science” in cancer prevention and health disparities, which he defined as “the systematic study of methods to promote the adoption and integration of evidence-based practice interventions and policies related to public health, clinical practice, and community settings.”

“Implementation science seeks to understand the behavior of healthcare professionals and other stakeholders as a key variable in the sustainable uptake adoption, and implementation of evidence-based interventions and practices” he said.

Implementation science has great potential in identifying and understanding factors that lead to health disparities, such as gaps in cancer screening in minority and underrepresented populations. Broader and deeper engagement of communities will play a major role in helping to understand and address disparities. Rivers predicted that health disparities will receive more attention at the health policy level in 2019.

Diversification of large databases will increase in the coming year, he added. Investigators already have implemented strategies in recruitment in tumor sample collection in diverse patient populations for cancer genomics studies and eventually molecular profiling.

The AACR has taken a lead role in developing a first-ever cancer disparities progress report, which will provide information and guidance in identifying health disparities and promoting health equity. In late 2018, AACR convened a Cancer Health Disparities think tank to identify next steps in addressing cancer health disparities.

“These initiatives are critical to conducting implementation science research, engaging the community, and ultimately advocating Congress on behavior of cancer research and making progress for cancer patients,” said Rivers.

• Primary Source

  AACR Cancer Research Catalyst

  Source Reference: Ravoori S “Experts forecase cancer research and treatment advances in 2019” AACR Cancer Research Catalyst 2019.

https://www.medpagetoday.com/hematologyoncology/othercancers/77330

Could a computer-designed Interleukin-2 be a safer cancer treatment?

Interleukin-2 (IL-2) has been prescribed to treat metastatic renal cell carcinoma and melanoma, but high toxicities have limited its use. Scientists have been working on various strategies to improve it, and now a team at the University of Washington has used computer programs to design a new protein that looks like IL-2 but doesn’t trigger dangerous side effects.

The new protein, dubbed Neo-2/15, resembles both IL-2 and IL-15, which is also being studied as an anticancer therapy. In tests on animal models, the synthetic drug activated cancer-fighting T cells just as the naturally occurring IL-2 does, and it slowed tumor growth, but it didn’t cause toxic side effects, the team reported in the journal Nature.

“Neo-2/15 has therapeutic properties that are at least as good as or better than naturally occurring IL-2, but it was computationally designed to be much less toxic,” said the study’s co-lead author, Umut Ulge, in a statement.

IL-2 is an effective treatment for some cancer patients that have exhausted other options. However, despite being on the market for decades, it has never really gained popularity, partially due to its precarious safety profile. Because IL-2 has a short serum half-life, it is often given at a high dose to achieve optimal cancer-killing effect, and that only increases the likelihood of severe complications, including death.

So the pharma industry has been pulling back from the IL-2 class in recent years. Novartis soldProleukin rights in the U.S. to Prometheus Laboratories in 2010 and ex-U.S. rights to Clinigen in 2018.

Natural IL-2 binds to three receptors: alpha, beta and gamma. While T-cell activation via beta and gamma receptors leads to therapeutic antitumor activity, IL-2’s binding to alpha receptor-expressing cells is believed to cause disastrous side effects as well as immunosuppression, the UW team explained in a statement.

To design their own protein, the researchers used a computer program called Rosetta that was developed in the lab of biochemist David Baker, the study’s leader. Using Rosetta, the team came up with Neo-2/15, which has surfaces that bind to IL-2 receptors beta and gamma but not the alpha receptor.

“This is the first example of a completely de novo designed protein which has very clear therapeutic anticancer potential. So this could be a first of many new drugs that have better properties than previous drugs,” said Baker in a recorded video interview.

Attempts to update IL-2 have seen their fair share of failures lately. Nektar Therapeutics’ long-acting IL-2 candidate NKTR-214, for example, had previously failed as a monotherapy. And top-line data from a phase 1/2 trial combining it with Bristol-Myers Squibb’s Opdivo also showed a reduced overall response rate from an earlier readout, prompting a bearish report from Plainview LLC.

Others are still pushing ahead with their IL-2 candidates. Alkermes is testing its ALKS 4230 in the monotherapy setting, and in September 2018 it expanded its ongoing phase 1 study to evaluate it in combination with Merck & Co.’s PD-1 inhibitor Keytruda. California biotech Synthorx recently got $131 million in an upsized IPO, and it’s looking to use the money to advance its lead molecule, Synthorin IL-2, into clinical trials this year.

There’s still a long way to go for Neo-2/15, but the UW team appears to be confident in its future.

“Neo-2/15 is very small and very stable. Because we designed it from scratch, we understand all its parts, and we can continue to improve it making it even more stable and active,” said the study’s co-lead author, Daniel-Adriano Silva, in a statement.

The next item on the team’s agenda is to enlarge the molecule to optimize it for use in people, said Baker. After further safety tests, a drug could be ready to enter clinical trials in a few years, the researchers reported.

https://www.fiercebiotech.com/research/could-a-computer-designed-il-2-be-a-safer-cancer-treatment

Piper remains buyer of Intuitive Surgical shares on ‘undeniable’ momentum

Piper Jaffray analyst JP McKim says this morning’s preliminary Q4 results and 2019 procedure guidance from Intuitive Surgical were both better than expected. The “strong” 13%-17% procedure guidance for 2019 far exceeded expectations and the “strong” system placements is a great leading indicator for future procedure growth, McKim tells investors in a research note titled “Undeniable Strong Momentum In The Business; Remain Buyers Here.” He believes Intuitive’s momentum is “very strong” and remains a buyer of the shares. This “high quality franchise” needs to be owned in portfolios as surgeries shift from open to robotic, McKim contends. He keeps an Overweight rating on Intuitive Surgical with a $625 price target. The stock in midday trading is up 6%, or $30.89, to $513.88.

https://thefly.com/landingPageNews.php?id=2846370

Genmab Achieves $75M Milestone in Collaboration with Janssen

Genmab to receive milestone payment of USD 75 million in DARZALEX collaboration

Milestone triggered by sales of DARZALEX reaching USD 2 billion in a calendar year

Genmab A/S (Nasdaq Copenhagen: GEN) announced today that it has achieved a USD 75 million sales volume milestone in its DARZALEX (daratumumab) collaboration with Janssen Biotech, Inc. The milestone was triggered by confirmation by Janssen that sales of DARZALEX reached USD 2 billion in the calendar year of 2018. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize DARZALEX.

We are very pleased that as the launch continues, DARZALEX has become available to so many more multiple myeloma patients in need, which is reflected in the achievement of this sales milestone. With the potential for further indications to be approved in the future, we look forward to even greater growth in the coming years, said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The milestone payment was included in the financial guidance issued by Genmaboriginally on February 21, 2018 and then reiterated in subsequent quarterly financial reports, most recently on November 14, 2018, and as such there is no change to the companys financial guidance for 2018.

https://www.marketscreener.com/GENMAB-1412914/news/Genmab-Achieves-USD-75-Million-Sales-Milestone-in-DARZALEX-daratumumab-Collaboration-with-Jansse-27844232/

HHS Secretary Azar says ‘need to see more’ drug price ‘good behavior’

Secretary of the U.S. Department of Health & Human Services Alex Azar tweeted: “We’ve seen some good behavior from companies such as Merck, Gilead, and Amgen, who announced lower prices for their drugs. We need to see more. @POTUS and I won’t stop until American patients see the lower prices they deserve.” Azar called out Merck (MRK), Gilead (GILD) and Amgen (AMGN) by name in his tweet. Other publicly traded large-cap drugmakers include AstraZeneca (AZN), Bristol-Myers (BMY), Eli Lilly (LLY), GlaxoSmithKline (GSK), Johnson & Johnson (JNJ), Novartis (NVS), Pfizer (PFE), Roche (RHHBY) and Sanofi (SNY)
https://thefly.com/landingPageNews.php?id=2846307