Supreme Court rejects HHS’ Medicare DSH changes

The U.S. Supreme Court on Monday ruled that HHS improperly changed its Medicare disproportionate-share hospital payments when it made billions of dollars in cuts.

In a 7-1 decision, the justices said HHS needed a notice-and-comment period for the Medicare DSH calculation change. Justice Neil Gorsuch wrote in the decision that HHS’ position for not following the procedure was “ambiguous at best.”

“Because affected members of the public received no advance warning and no chance to comment first, and because the government has not identified a lawful excuse for neglecting its statutory notice-and-comment obligations, we agree with the court of appeals that the new policy cannot stand,” Gorsuch wrote.

The case was highly technical, and hinged on dueling interpretations of agency activity on what constitutes a “substantive legal standard” in a payment policy change to Medicare.

Under the new Medicare DSH formula, the CMS began to lump Medicare Advantage enrollees in with traditional Medicare enrollees to calculate a hospital’s DSH payment.

But Medicare spending is about $700 billion per year, and the program covers nearly one-fifth of Americans. 
“Not only has the government failed to document any draconian costs associated with notice and comment, it also has neglected to acknowledge the potential countervailing benefits,” Gorsuch wrote. “Notice and comment gives affected parties fair warning of potential changes in the law and an opportunity to be heard on those changes—and it affords the agency a chance to avoid errors and make a more informed decision.”

The majority opinion also emphasized the size and scope of Medicare, noting that “even seemingly modest modifications to the program can affect the lives of millions.”
“As Medicare has grown, so has Congress’s interest in ensuring that the public has a chance to be heard before changes are made to its administration,” Gorsuch wrote.

During oral arguments in the case in January, Gorsuch and Justice Sonia Sotomayor doubled down on the economic magnitude of the change, which HHS estimated to be $3 billion to $4 billion between fiscal 2005 and 2013.

Justice Stephen Breyer dissented from the majority, and Justice Brett Kavanaugh recused himself because he participated in the U.S. Court of Appeals for the District of Columbia Circuit ruling that the Supreme Court upheld.

Breyer wrote he believed the government had the legal grounds to skip the public comment period in this policy.
“The statutory language, at minimum, permits this interpretation, and the statute’s history and the practical consequences provide further evidence that Congress had only substantive rules in mind,” he wrote. “Importantly, this interpretation of the statute, unlike the court’s, provides a familiar and readily administrable way for the agency to distinguish the actions that require notice and comment from the actions that do not.”

https://www.modernhealthcare.com/legal/supreme-court-rejects-hhs-medicare-dsh-changes

A bright future for CNS and Alzheimer’s?

Swiss biotech Asceneuron is developing what could be the first treatment for progressive supranuclear palsy (PSP), a rare CNS condition that can impair balance, movement, vision, and speech. We spoke to CEO and founder Dirk Beher to get his views on the remaining challenges of tackling diseases like PSP and Alzheimer’s.

Tell us about ASN120290. Why are you targeting PSP?

ASN120290 is a small molecule inhibitor of the O-GlcNAcase enzyme. In preclinical models inhibiting this enzyme can essentially prevent toxic tau tangles from forming.

We are now preparing to move the molecule into progressive supranuclear palsy (PSP). PSP is a small enough indication that we could look at efficacy with a patient population that is relatively well defined. Also, PSP is one of the very few CNS diseases which is exclusively driven by tau. At the level of pathology, it is so to speak a “cleaner” disease compared to Alzheimer’s disease.

Needless to say, PSP is terrible disease. When you talk to people who are looking after loved ones with PSP you see that it’s a very disheartening disease for them to watch.

What barriers have prevented there from being other treatments available for PSP in the past?

Historically, there haven’t been an awful lot of trials compared to a large indication such as Alzheimer’s because it’s an orphan disease. It’s also only recently that patients have become more organised, that diagnostic criteria have become fully established and that knowledge and awareness have generally increased. I think this is why PSP was neglected beforehand. Also, it’s fair to say that with the more recent interest of the industry in tau that more drugs are worth exploring in this indication.

What kind of trial results have you seen so far?

In phase 1 studies we have seen substantial drug exposure in the central nervous system, in the range that predicts target engagement required for efficacy. We are also currently wrapping up a PET tracer study for target engagement. We expect to present the results at the Alzheimer’s International Conference in Los Angeles in July.

Asceneuron is focused on tau. Many companies have been dropping Alzheimer’s drugs related to beta-amyloid build-up. Do you see that trend continuing, and do you think tau is going to be the priority for researchers over the next few years?

Yes. I’ve worked on a number of beta-amyloid programmes and I think people have been attracted to this by the strong genetics underlying beta amyloid. There is a clear link to disease, but we still have to work out what exactly it is at the end of the day.

We have seen a couple of antibodies fail in the clinic targeting soluble entities which do not remove plaques. Unfortunately, antibodies that remove plaques did not fare better either. Hence, we like to spread our bets broader these days. I think tau is certainly one of the key areas here.

One of the reasons why people are really excited about tau is because we now have a greater understanding of how it is closely linked to disease progression. Essentially, there are imaging agents (PET tracers) which specifically bind to the neurofibrillary tangles, the tau aggregates in the brains. The amount of tau tracer binding and the increase over time is closely linked to the clinical stage and progression in Alzheimer’s disease. Then you can also ask the question of where is the tau deposition happening. We now know how to look at both the quantity of tau and where it happens. It is worth pointing out that this seems to work well for Alzheimer’s disease whereas for PSP and other tauopathies it appears that novel tau tracers will need to be developed.

There are quite a few companies out there that are deprioritising CNS, and the burden of it is falling on smaller companies like yourself. Do you think it will become a priority again for bigger companies, or will it remain something that is perhaps better served by smaller companies?

I think we need the larger companies to be engaged in the CNS space given the unmet need and interdependencies. Even for smaller companies, when we do our fundraising, if it’s only us it’s very difficult to build excitement if we’re kind of the lone wolf. It’s always useful to point to bigger companies that are doing studies, that have a network and could become a future partner.

Hopefully the area will evolve similarly to immuno-oncology. As soon as someone has positive data, even with a small effect size, the pendulum might swing around again. We have seen some very big companies going out, but given the competitive nature of areas like immuno-oncology, people may want to get back to CNS when they see that there is something there.

Are there any other areas in CNS that you feel are underserved at the moment?

There are still quite a number of underserved diseases out there. Neuropsychiatric indications such as schizophrenia are one example. Overall, when you think about unmet need, CNS scores pretty high in my view.

Were there any other more general challenges of working in the area that still need addressing?

One is finding and treating the patients early enough. We need more early diagnostics criteria and tools. The challenge is that when people become symptomatic, they have already lost a large number of the functionality in the brain. Parkinson’s disease is a good example. Patients have already lost over half of their dopaminergic neurons by the time they become symptomatic.

Are you hopeful for the future of CNS and Alzheimer’s?

I’m hopeful that by diversifying, we may find therapies that show some kind of efficacy. Then the area can develop in a similar way to immuno-oncology. My hope is that we can take some of those drugs and can combine these things to really get to a meaningful treatment.

About the interviewee

Dirk Beher is the chief executive officer, a founder and a member of the Board of Directors of Asceneuron. Dirk has more than 25 years of experience in the field of Alzheimer’s disease/neurodegeneration and spent over 19 years in pharmaceutical drug discovery including senior research positions around the globe at Merck Sharp & Dohme, Amgen and Merck KGaA.

A bright future for CNS and Alzheimer’s?

Relax criteria to increase sign-ups to cancer trials, says ASCO

Only 3% of patients with cancer in the US enrol on a clinical trial – and the American Society of Clinical Oncology (ASCO) is concerned that outdated and restrictive eligibility criteria could be hindering research.

The organisation has used its annual meeting in Chicago to call for some of these outmoded eligibility criteria to be dropped after a study showed that relaxing three rules used to screen patients almost doubled the number of patients on a dummy lung cancer trial.

The research looked at the health records of 10,500 patients from 2011 to 2018 with advanced non-small cell lung cancer on ASCO’s cancer database.

Researchers looked at the number of patients eligible for trials using traditional criteria, and using new proposed criteria from ASCO and Friends Of Cancer Research.

These allow for brain metastases, previous or current cancer diagnoses, and creatine clearance levels as low as 30 millilitres per minute, which can indicate kidney damage or impaired function.

Traditional criteria do not allow for these conditions and exclude patients with creatine clearance levels less than 60 millilitres per minute

Using expanded criteria would nearly double the percentage of patients eligible to sign up, from 52.3% to 98.5%.

The criteria would allow for patients with brain metastases, previous or concurrent cancers, and limited kidney function to sign up, and would also result in a higher percentage of older patients joining.

In the broadened trial 22% of patients were older than 75, compared with 16% using the traditional criteria.

There were more women on the trial, rising from 40% to 44%, more Stage IV diagnosis, increasing from 55% to 60%.

Non-squamous types of lung cancer increased from 45% to 47% and there were more never smokers, raising the rate from 13% to 16%.

Lead study author Donald Harvey, director of the Winship Cancer Institute of Emory University’s Phase 1 Clinical Trials Section, noted that eligibility criteria are based on “antiquated safety concerns” that are no longer valid because of developments in supportive care.

The message from Harvey in a presentation of findings at an ASCO press conference was clear, with a clarion-call to use the more relaxed screening criteria. “We urge all clinical trial sponsors to adopt these criteria,” he said.

Relax criteria to increase sign-ups to cancer trials, says ASCO

Argus: Aptorum Group Ltd

Aptorum Group Ltd., a Hong Kong-based pharmaceutical company, develops and commercializes therapeutic and diagnostic technologies to treat unmet medical needs. The company also focuses on the development of surgical robotics and medical devices and operates outpatient clinics.

COMPANY HIGHLIGHTS
* APM: Addressing Orphan Indications and Unmet Needs
* In our view, Aptorum has compiled an impressive pipeline of early-stage assets that we
expect to drive significant value, both from internal development and external collaborations.
* In mid-2018, Aptorum launched a medical clinic in Hong Kong. Over time, we expect
revenue from this business to help mitigate the company’s R&D cash burn.
* In December 2018, Aptorum raised approximately $11 million from an initial public offering. The Company ended 2018 with $27.1 million in cash/restricted cash and marketable securities, which should be sufficient to advance at least one of its lead clinical programs to Phase I trials.
* Based on our sum-of-the-parts NPV valuation for the company’s lead programs and IP and technology assets, we arrive at a fair value estimate of $24 per share, well above current levels.
INVESTMENT THESIS
Aptorum Group Ltd., based in Hong Kong, is developing a range of therapeutic and diagnostic technologies to treat unmet medical needs. Its primary focus areas include infectious diseases, neurology, gastroenterology, and oncology. Aptorum is also developing product candidates in surgical robotics and medical devices. In mid-2018, the company launched an outpatient clinic in Hong Kong to treat chronic diseases resulting from modern sedentary lifestyles and an aging population.

https://www.argusresearch.com/PDFDownloader3.aspx?id=MDAwMDAwNzEwNA==aAB0AHQAcAA6AC8ALwByAGUAcwBvAHUAcgBjAGUAcwAuAGEAcgBnAHUAcwByAGUAcwBlAGEAcgBjAGgALgBjAG8AbQAvAHIAZQBwAG8AcgB0AHMALwAwADAALwAwADAALwAzADYALwAzADMALwAzADMALQA2ADAANABCADEAMAAxAEYALQBFADAAMgA0AC0ANAA4AEEARgAtAEIAOQBDADEALQBBADcAOAA2ADgAMAAyAEIARgBBADEAOAAuAHAAZABmAA==

‘CRISPR baby mutation’ seen significantly increasing mortality

A genetic mutation that a Chinese scientist attempted to create in twin babies born last year, ostensibly to help them fend off HIV infection, is also associated with a 21% increase in mortality in later life, according to an analysis by University of California, Berkeley, scientists.

The researchers scanned more than 400,000 genomes and associated health records contained in a British database, UK Biobank, and found that people who had two mutated copies of the gene had a significantly higher death rate between ages 41 and 78 than those with one or no copies.

Previous studies have associated two mutated copies of the gene, CCR5, with a fourfold increase in the death rate after influenza infection, and the higher overall mortality rate may reflect this greater susceptibility to death from the flu. But the researchers say there could be any number of explanations, since the protein that CCR5 codes for, and which no longer works in those having the mutation in both copies of the gene, is involved in many body functions.

“Beyond the many ethical issues involved with the CRISPR babies, the fact is that, right now, with current knowledge, it is still very dangerous to try to introduce mutations without knowing the full effect of what those mutations do,” said Rasmus Nielsen, a UC Berkeley professor of integrative biology. “In this case, it is probably not a mutation that most people would want to have. You are actually, on average, worse off having it.”

“Because one gene could affect multiple traits, and because, depending on the environment, the effects of a mutation could be quite different, I think there can be many uncertainties and unknown effects in any germline editing,” said postdoctoral fellow Xinzhu “April” Wei.

Wei is first author and Nielsen is senior author of a paper describing the research that will appear online on Monday, June 3, in the journal Nature Medicine.

Mutation prevents HIV infection

The gene CCR5 codes for a protein that, among other things, sits on the surface of immune cells and helps some strains of HIV, including the most common ones, to enter and infect them. Jiankui He, the Chinese scientist who last November shocked the world by announcing he had experimented with CCR5 on at least two babies, said he wanted to introduce a mutation in the gene that would prevent this. Naturally-occurring mutations that disable the protein are rare in Asians, but a mutation found in about 11% of Northern Europeans protects them against HIV infection.

The genetic mutation, ∆32 (Delta 32), refers to a missing 32-base-pair segment in the CCR5 gene. This mutation interferes with the localization on the cell surface of the protein for which CCR5 codes, thwarting HIV binding and infection. He was unable to duplicate the natural mutation, but appears to have generated a similar deletion that would also inactivate the protein. One of the twin babies reportedly had one copy of CCR5 modified by CRISPR-Cas9 gene editing, while the other baby had both copies edited.

But inactivating a protein found in all humans and most animals is likely to have negative effects, Nielsen said, especially when done to both copies of the gene — a so-called homozygous mutation.

“Here is a functional protein that we know has an effect in the organism, and it is well-conserved among many different species, so it is likely that a mutation that destroys the protein is, on average, not good for you,” he said. “Otherwise, evolutionary mechanisms would have destroyed that protein a long time ago.”

After He’s experiment became public, Nielsen and Wei, who study current genetic variation to understand the origin of human, animal and plant traits, decided to investigate the effect of the CCR5-∆32 mutation using data from UK Biobank. The database houses genomic information on a half million U.K. citizens that is linked to their medical records. The genomic information is much like that acquired by Ancestry.com and 23andMe: details on nearly a million individual variations in the genetic sequence, so-called single nucleotide polymorphisms (SNPs).

Two independent measures indicated a higher mortality rate for those with two mutated genes. Fewer people than expected with two mutations enrolled in the database, indicating that they had died at a higher rate than the general population. And fewer than expected survived from ages 40 to 78.

“Both the proportions before enrollment and the survivorship after enrollment tell the same story, which is that you have lower survivability or higher mortality if you have two copies of the mutation,” Nielsen said. “There is simply a deficiency of individuals with two copies.”

Because the ∆32 mutation is relatively common in Northern Europeans, it must have been favored by natural selection at some point, Nielsen said, though probably not to protect against HIV, since the virus has circulated among humans only since the 1980s.

Wei said that some evidence links the mutation to increased survival after stroke and protection against smallpox and flaviviruses, a group that includes the dengue, Zika and West Nile viruses.

Despite these possible benefits, the potential unintended effects of creating genetic mutations, in both adult somatic cells and in embryonic, germline cells, argue for caution, the researchers said.

“I think there are a lot of things that are unknown at the current stage about genes’ functions,” Wei said. “The CRISPR technology is far too dangerous to use right now for germline editing.”

###

This work was supported by the National Institutes of Health (R01GM116044).

https://www.eurekalert.org/pub_releases/2019-06/uoc–cbm052919.php

American Pain Society Seeks OK to Call It Quits

The American Pain Society may soon vote itself out of existence, blaming soaring legal costs to fight litigation that alleges the organization, along with medical associations, acted as “front groups” for opioid drugmakers that gave them financial support.

“It is with heavy hearts that we write to inform you that it is the recommendation of the Board of Directors that [[the] American Pain Society (APS) cease its business operations,” said an email the board sent to the society’s membership Wednesday.

“APS has been named as a defendant in numerous spurious lawsuits and is subject to numerous subpoenas … (and) was unsuccessful in its attempts to resolve these lawsuits without the need for what will no doubt be lengthy and expensive litigation,” the May 22 message to members said.

With an 11 to 1 vote, the APS board voted to recommend that its members approve the filing of a Chapter 7 bankruptcy petition, under which the group would dissolve with an independent trustee disposing of its assets.

The email said at least 10% of its 1,173 eligible members must vote, with a majority of those approving the bankruptcy filing by 11:55 p.m. CDT Wednesday, May 29, for it to go through.

APS spokesman Chuck Weber said that if members vote for the board’s recommendation, the organization’s monthly Journal of Pain, numerous research grants, a young investors fund, and the group’s annual scientific meeting would disappear or be taken over by other organizations. The 2020 annual meeting had already been cancelled; the group’s president recently reported that membership had declined by nearly half since 2014, and meeting attendance had fallen off markedly as well.

In shock

“I’m in shock,” said Steven Stanos, DO, a past president of the American Academy of Pain Medicine, and medical director of pain services at Swedish Health System in Seattle, when told about the board email Wednesday. “This is a great association that’s done a lot of great work for patients and pain research.”

The AAPM and the American Geriatric Society are also named as co-defendants in at least one lawsuit that filed against numerous drug manufacturers and distributors by the Illinois Public Risk Fund, the state’s worker compensation pool.

APS officials would not speak on the record about the specific reasons why professional pain organizations are being named as defendants in these lawsuits that primarily target opioid manufacturers such as Purdue Pharma, Endo Pharmaceuticals, and Johnson & Johnson.

But Robert Twillman, PhD, executive director of the now defunct Academy of Integrative Pain Management, said that trade organizations such as the APS are being named because opioid company money supported them, including his own, for years. And some outsiders believe the trade groups “were a front for their [opioid manufacturers’] marketing activities.”

“People outside the organization — some of them — had that concern but those inside the organization who saw what we were actually doing with the money didn’t have that concern. We advocated for the appropriate access for patients in need, but we also advocated for access to acupuncture and massage therapy and chiropractic and all the other things we have as treatments,” he said.

Pharma money dried up

With national public attention now focused on opioid overprescribing and the now-vilified guidelines that contributed to it, those sources of funding have dried up — either because the trade organizations now refuse it or because drugmakers stopped doling it out. That, along with declining membership, is what happened to the AIPM in January.

“Medical organizations were supported to some degree by pharmaceutical funding,” Twillman said. “And in the pain space, unfortunately, the vast majority of that money comes from opioid manufacturers. So when they started being sued, and part of the allegation was that they were supporting organizations like ours as a front for their marketing activities, a logical thing for them to do was withdraw their support.” In the case of his group, the AIPM, about $1 million, nearly half of its budget, came from pharma, he said.

One official familiar with the APS board deliberations, who declined to be named for this story, said this:

“Organizations like APS and the AAPM and others are being named in these complaints because they’re being accused of writing recommendations and guidelines favorable to the use of opioids and some claim those guidelines were supported financially by the pharma companies.”

But, he added, “any guidelines that were published were published on the basis of the evidence that was known at the time. Medical science changes, and something that was published in 2009 might not be as germane in 2019, given what’s known about these drugs 10 years later.”

Litigation purgatory

In a letter posted recently on the APS website, its president, William Maixner, DDS, PhD, noted the group has been named in several lawsuits against opioid manufacturers filed in Illinois and in California, now transferred to an Ohio Multi-District litigation court.

“Monetary damages are not the goal for the vast majority of these legal claims, and plaintiffs are currently NOT prosecuting claims against [the] APS, which means we’re in ‘litigation purgatory,'” Maixner wrote. “We are being kept on the sidelines while they fight other parties.”

However, the APS has had to respond to “several subpoenas or demands for information … [that] are draining resources — both time and money. It impacts our ability to secure adequate insurance coverage and diminishes our risk tolerance. Our communication and advocacy efforts have been thwarted because of our inability to speak freely,” he said.

What the APS may have genuinely contributed to harmful and fatal overprescribing is up for debate and judicial consideration. Some investigations, however, have concluded that the APS and like organizations share in the blame.

On May 22, in fact, the APS was specifically named in a report by U.S. Rep. Katherine Clark (D-Mass.) and U.S. Rep. Hal Rogers (R-Ky.), entitled “Corrupting Influence: Purdue & the WHO.”

“The American Pain Society and its global arm, the International Association for the Study of Pain (IASP), promote opioid use, especially for chronic, noncancer pain [and it] is an organization with longstanding ties to Purdue that were the subject of a Senate investigation in 2017,” the House members’ report said. “The investigation revealed that multiple organizations that claimed to be independent patient advocacy groups, including the American Pain Society, received significant payments from opioid manufacturers.” The report also charged that the APS was “affiliated with multiple prominent individuals with connections to the opioid industry.”

A past APS president, Dennis Turk, received “personal fees from opioid manufacturers,” the report said. Another past president and former APS board chairman, James Campbell, is “credited with first saying pain should be treated as ‘the fifth vital sign,’ which became a key component of opioid manufacturer-funded promotional materials encouraging higher prescribing rates.”

Another Congressional report, issued by the U.S. Senate Committee on Homeland Security & Governmental Affairs, “Fueling an Epidemic,” said that from 2012 through 2017, the American Pain Society received $962,724, with more than half of that from Purdue. It was one of 14 specialty groups that received nearly $9 million from five opioid manufacturers, including Janssen, Depomed, Insys, and Mylan.

A legal shotgun

Robert Wailes, MD, chairman of the California Medical Association’s board of trustees and a San Diego-area pain specialist, lamented the lawsuits, calling them “a shotgun approach to include as many defendants as possible.”

Practically speaking, he continued, they are merely after deep pockets of pharma, with no blame for most physicians or their organizations, and said the lawsuits are abusing the legal system.

“It is very, very costly to have attorneys represent you and be present long enough to get you dropped from any individual case. If you multiply this by scores of lawsuits in different venues the costs are really enormous.”

Wailes, who also is the AAPM’s representative to the American Medical Association, stressed that he was speaking only for himself rather than any organization he represents.

Others emphasized that if the APS does dissolve, it will be a shame.

“It would be a tremendous loss nationally for pain education and pain research,” said Rollin ‘Mac’ Gallagher, MD, editor of the journal Pain Medicine, the official journal of the AAPM, and the recently retired national director for pain management for the Department of Veterans Affairs. Gallagher blamed the opioid epidemic not on the APS or other specialty provider groups’ guideline advocacy, but rather that practitioners “were not trained to take care of pain appropriately.”

Added Beth Darnall, PhD, pain researcher associate professor of anesthesiology at Stanford University’s Pain Management Center, “It would be a tremendous loss for pain education and pain research. They’ve really been a go-to place for researchers, and clinicians.”

https://www.medpagetoday.com/painmanagement/painmanagement/80054

Amgen: 1st Data on Investigational KRASG12C Inhibitor AMG 510 At ASCO

Amgen (NASDAQ: AMGN) today announced the first clinical results from a Phase 1 study evaluating investigational AMG 510, the first KRAS^G12C inhibitor to reach the clinical stage. In the trial, there were no dose-limiting toxicities at tested dose levels. AMG 510 showed anti-tumor activity when administered as a monotherapy in patients with locally-advanced or metastatic KRAS^G12C mutant solid tumors. These data are being presented during an oral session at the 55^th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“KRAS has been a target of active exploration in cancer research since it was identified as one of the first oncogenes more than 30 years ago, but it remained undruggable due to a lack of traditional small molecule binding pockets on the protein. AMG 510 seeks to crack the KRAS code by exploiting a previously hidden groove on the protein surface,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “By irreversibly binding to cysteine 12 on the mutated KRAS protein, AMG 510 is designed to lock it into an inactive state. With high selectivity for KRAS^G12C, we believe investigational AMG 510 has high potential as both a monotherapy and in combination with other targeted and immune therapies.”

The Phase 1, first-in-human, open-label multicenter study enrolled 35 patients with various tumor types (14 non-small cell lung cancer [NSCLC], 19 colorectal cancer [CRC] and two other). Eligible patients were heavily pretreated with at least two or more prior lines of treatment, consistent with their tumor type and stage of disease. The primary endpoint is safety, and key secondary endpoints include pharmacokinetics, objective response rate (assessed every six weeks), duration of response and progression-free survival. Patients were enrolled in four dose cohorts – 180 mg, 360 mg, 720 mg and 960 mg, taken orally once a day.

Five out of 10 evaluable patients with NSCLC experienced a partial response (PR), and another four had stable disease (SD), for a disease control rate (DCR) of 90 percent (9/10).¹ All five patients with response to therapy had a treatment duration of 7.3-27.4 weeks at data cutoff and remain active on treatment. One patient with PR improved further to a complete response of the target lesions at week 18, post data cutoff.

In addition, 13 of 18 evaluable patients with CRC achieved SD, with the majority of CRC patients treated at the first two dose levels. Twenty-six patients remain on study and nine have discontinued.

Treatment-related adverse events (AEs) were primarily grade 1 events (approximately 68 percent). Two grade 3 treatment-related AEs were reported (anemia and diarrhea). No grade 4 treatment-related AEs and no serious treatment-related AEs were reported. Enrollment into dose expansion is underway.

“While there’s been significant progress in treating solid tumor cancers overall with targeted therapies, patients with the KRAS^G12C mutation have not benefited from these advances,” said Marwan G. Fakih, M.D., clinical study investigator and co-director of the Gastrointestinal Cancer Program, City of Hope, Duarte, Calif. “In this early Phase 1 trial, investigational AMG 510 showed encouraging anti-tumor activity. We look forward to further investigating AMG 510 with the goal of closing the treatment gap for patients with this type of mutation.”

Amgen Webcast Investor Meeting
Amgen will host a webcast investor meeting at ASCO 2019 on Monday, June 3 at 6:30 p.m. CT. David M. Reese, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen’s clinical development team and clinical investigators, will participate at the investor meeting to discuss Amgen’s oncology program and data presented at ASCO 2019. Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given at certain investor and medical conferences, can be accessed on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

https://www.biospace.com/article/releases/amgen-announces-first-clinical-data-evaluating-novel-investigational-krasg12c-inhibitor-amg-510-at-asco-2019/