Seema Verma, Administrator of the Centers for Medicare & Medicaid Services, or CMS, said in a memo that insurers and pharmacy benefit managers can assume drug-pricing rebates in Medicare Part D will still exist as they design their 2020 plans, reported Axios’ Bob Herman. The Trump administration has proposed eliminating such Medicare rebates beginning in 2020, the report noted. Pharmacy benefit managers include Express Scripts (ESRX), CVS Health (CVS) and UnitedHealth (UNH). Drug distributors include AmerisourceBergen (ABC), Cardinal Health (CAH) and McKesson (MCK). Publicly traded drugmakers include AstraZeneca (AZN), Bristol-Myers (BMY), Eli Lilly (LLY), GlaxoSmithKline (GSK), Johnson & Johnson (JNJ), Merck (MRK), Novartis (NVS), Pfizer (PFE), Roche (RHHBY) and Sanofi (SNY). Publicly traded health insurers include Anthem (ANTM), Centene (CNC), Cigna (CI), Health Net (HNT), Humana (HUM), Molina Healthcare (MOH), UnitedHealth (UNH) and WellCare (WCG).
Friday, April 5, 2019
LivaNova pullback on disappointing Q1 results overdone, says Piper Jaffray
Piper Jaffray analyst Matt O’Brien noted that LivaNova (LIVN) shares are trading down over 25% after the company preannounced disappointing Q1 revenues, which he views as overdone. At current levels, the stock reflects a “modest multiple” for the core business and “essentially nothing” to LivaNova’s pipeline, said O’Brien, who thinks the company’s pipeline opportunity in Treatment-Resistant Depression, or TRD, is significant. The company blamed its neuromodulation sales miss to the launch of a competitive drug product from GW Pharma (GWPH), but O’Brien believes this business should stabilize by the end of the year, he added. He maintains an Overweight rating on LivaNova shares with a price target of $120.
https://thefly.com/landingPageNews.php?id=2889297
https://thefly.com/landingPageNews.php?id=2889297
Stephens Reiterates Overweight Rating on Myriad Genetics
Stephens analyst Drew Jones reiterated an Overweight rating and $52 target price.
Janney: Amicus Has Significant Upside From Gene Therapy Pipeline
Amicus Therapeutics, Inc. FOLD 3.16% has an extensive portfolio of novel therapies for rare diseases with a focus on lysosomal storage disorders, according to Janney Montgomery Scott.
The Analyst
Janney’s Yun Zhong initiated coverage of Amicus Therapeutics with a Buy rating and $20 fair value estimate.
The Thesis
Galafold, a next-gen enzyme replacement therapy, is well-positioned to gain significant share of the expanding Fabry disease market, Zhong said in the Friday initiation note.
While global ERT sales reached nearly $1.5 billion in 2018, a large number of patients are not receiving treatment — mainly due to the requirement of biweekly IV infusions, the analyst said. Against this backdrop, Galafold offers a highly favorable alternative treatment, as it offers oral dosing with comparable efficacy, he said.
A large number of undiagnosed or misdiagnosed Fabry patients carry mutations, Zhong said, adding that such patients will be more amenable to Galafold treatment.
Expressing optimism regarding the therapy’s rapid penetration due to increased disease awareness and improved diagnostics, Zhong said that Amicus’ $500-million estimate could prove highly conservative.
With the Celenex acquisition, Amicus gained access to one the broadest gene therapy pipelines in the industry, the analyst said. The acquisition, along with the UPenn collaboration and the company’s expertise, could help Amicus build a platform that will support its exponential growth in the coming years, he said.
The company has another ERT in pivotal Phase III clinical development for Pompe disease. Given the strong Galafold launch trend and encouraging Pompe data to date, there seems to be limited downside risk for Amicus, according to Janney.
23andMe Breast, Ovarian Risk Test Misses Nearly 90% of BRCA Mutation Carriers
A study led by researchers at Invitae has found that 23andMe’s direct-to-consumer BRCA test, which tests for three common variants in the BRCA1 and BRCA2 genes and is authorized by the US Food and Drug Administration, misses almost 90 percent of BRCA mutation carriers, both in those with and those without a personal or family history of cancer.
In addition, it misses almost 20 percent of BRCA mutations in those of self-reported Ashkenazi Jewish descent because it doesn’t test for them.
The results of the study, which looked at data from almost 125,000 de-identified individivuals who had been referred to Invitae for diagnostic testing with one of the firm’s cancer risk tests, was presented yesterday at the American College of Medical Genetics and Genomics annual meeting by Edward Esplin, a clinical geneticist at Invitae.
Esplin told GenomeWeb that the study, which did not mention 23andMe by name, was meant to criticize a screening strategy with an FDA-authorized DTC test that appears to have limited clinical utility rather than to criticize 23andMe for offering the test.
In his presentation, he pointed out that the FDA’s authorization for the test last year “sounds more like a warning than an approval.” FDA cautioned that the test, which examines three founder mutations in the BRCA genes that are common in the Ashkenazi Jewish population, does not assess more than 1,000 other known BRCA mutations, so a negative result does not rule out someone is a mutation carrier. It also advises that positive test results should not be used to determine any treatments without confirmatory testing and genetic counseling.
23andMe has been widely criticized for offering the test, and many experts have said that customers receiving a negative result may falsely assume they do not have an elevated breast or ovarian cancer genetic risk. The company has countered that it believes its customers do understand the limitations of the test and that many who receive a positive result may not have learned about it otherwise.
However, Esplin said, up until now, there has been no data available on the implications of a DTC strategy for breast and ovarian cancer risk testing that is limited to only three mutations.
For their ongoing study, which involves clinical collaborators from the Dana-Farber Cancer Institute, Yale University, and Georgetown University, the researchers are planning to analyze data from more than 200,000 de-identified individuals tested by Invitae and to include clinical vignettes of patients they have seen. Yesterday, Esplin presented preliminary results from three cohorts totaling almost 125,000 de-identified persons who had undergone diagnostic cancer risk testing at Invitae for different reasons.
Of these, 119,300 were referred for diagnostic hereditary breast and ovarian cancer genetic testing because of a personal or family history of cancer. The company offers a variety of cancer risk panels of different sizes that include the BRCA genes, and Esplin did not specify which of these panels were used in testing patients.
Another 5,200 patients had undergone Invitae testing without a reported personal or family history of cancer because they had sought genetic testing to inform their own health. These included patients who had taken one of Invitae’s proactive health genetic tests, such as the Cancer Screen or the Genetic Health Screen.
A third cohort consisted of 100 patients who were referred to Invitae for confirmatory testing after receiving a positive result on a DTC test from 23andMe and others.
In the indication-based cohort, Invitae found that 11 percent had a pathogenic or likely pathogenic mutation in a hereditary cancer syndrome-associated gene, while 89 percent had a negative result.
Of the more than 4,700 patients in whom Invitae found a pathogenic or likely pathogenic mutation in BRCA1 or BRCA2, only 12 percent had one of the three Ashkenazi Jewish founder mutations, while 88 percent had a different mutation. Those patients would not have obtained a positive result had they taken the limited 23andMe test, which is “clearly very concerning,” Esplin said.
Within the BRCA-positive group, 94 percent of those who said they were not of Ashkenazi Jewish descent had a mutation that was not included in the 23andMe test.
Even within some self-reported Ashkenazi Jewish individuals with a BRCA mutation, 23andMe would have delivered a negative result: 19 percent of them had a mutation other than the three founder mutations.
Among the 5,000 or so “healthy” patients who underwent Invitae testing without a reported family or personal history of cancer – a group that might be more representative of the type of person seeking out 23andMe’s BRCA test because they would not be covered by current screening guidelines – the results were no different: only 12 percent of those who were found to have a mutation in BRCA1 or BRCA2 had one of the three mutations tested by 23andMe, and 88 percent had a different mutation.
Finally, Invitae was only able to confirm a positive DTC result – many of them in BRCA1 or BRCA2 – for half of the 100 individuals who were referred to it for confirmatory testing. Esplin said this result is consistent with other data published last year and points to the potential for false-positive results from a DTC screening strategy. Not all of the 100 had their DTC test from 23andMe, he said, and about a third had obtained their positive result not directly from the test provider but by submitting their raw data to a third party for analysis.
Overall, Esplin said, the data confirms the caveats contained in the FDA’s authorization of 23andMe’s BRCA test and suggests that confirmatory testing is needed for those with a positive result as well as those with a negative result from limited DTC testing. “Both of these types of individuals should receive clinical genetic testing,” he said.
This, Esplin and his colleagues wrote in their conference abstract, “begs the question of what role, if any, does DTC testing for these three mutations really play in the healthcare of individuals who either have an indication for testing or are seeking to know their risks.”
Soliton Initiated Clinical Trials for Treatment of Cellulite in Humans
Soliton, Inc., (NASDAQ: SOLY) (“Soliton” or the “Company”), a medical device company with a novel and proprietary platform technology licensed from The University of Texas on behalf of the MD Anderson Cancer Center (“MD Anderson”), today summarized its efforts to conduct a proof of concept clinical trial for the treatment of cellulite based on Institutional Review Board (“IRB”) approval of the study. The study was initiated after positive results in animal studies indicated the potential for a higher-energy version of its acoustic shockwave technology to affect the factors contributing to the formation of cellulite.
The study treated each thigh of five patients (n=10) with a higher-energy version of Soliton’s acoustic shockwave device with the intent to evaluate safety and efficacy in the treatment of cellulite. The study is designed to evaluate results at both the 12-week and 26-week timepoints from initial treatment in order to assess both near-term and long-term effects.
“Our preclinical data led us to believe we could have a significant impact on the reduction of cellulite,” commented Dr. Chris Capelli, Soliton’s President and CEO. “This is especially significant since our technology should represent a non-invasive, pain free treatment that requires no anesthesia and involves no bruising, discomfort or downtime. If we are right, we believe this could be a major breakthrough in the treatment of cellulite.”
Soliton, Inc. is a medical device company with a novel and proprietary platform technology licensed from MD Anderson. The Company’s first planned commercial product is designed to use rapid pulses of designed acoustic shockwaves in conjunction with existing lasers to accelerate the removal of unwanted tattoos (RAP device). In addition, higher energy versions of acoustic pulse devices are in early stages of development for potential stand-alone treatment of cellulite and other indications. Both products are investigational and are not available for sale in the United States.
Clues to what causes immuno-oncology drug resistance
Checkpoint-inhibiting drugs have revolutionized the treatment of melanoma and other cancers by freeing up the immune system to attack tumors. But the medicines don’t work for as many as half of patients, even when they’re combined with other cancer treatments.
Now, two separate research groups have uncovered different mechanisms of immuno-oncology drug resistance. One involves the gut microbiome, while the other is related to vesicles that are produced by cancer cells.
First, a worldwide consortium of 40 scientists led by Sanford Burnham Prebys released a study demonstrating that the gut microbiome orchestrates the immune system’s response to cancer. They published their observations in the journal Nature Communications.
The Sanford Burnham Prebys-led team made the discovery by working with mice engineered to lack RING finger protein 5 (RNF5), a gene that normally works to clear damaged proteins from cells. These mice mounted a strong immune response to melanoma, so the researchers used bioinformatics technology to identify 11 bacterial strains that were plentiful in the animals’ guts. They then transferred the bacteria to normal mice and found it also induced a strong immune response to melanoma in those animals.
The researchers mapped out the immune components that were active in the gut, and they discovered that a signaling pathway called the unfolded protein response (UPR) was reduced when immune cells were activated. Then they studied tumor samples from people who had received checkpoint inhibitors, and they found reduced UPR expression correlated with a good response to treatment.
The findings “identify a collection of bacterial strains that could turn on anti-tumor immunity and biomarkers that could be used to stratify people with melanoma for treatment with select checkpoint inhibitors,” said senior author and Sanford Burnham Prebys professor Ze’ev Ronai, Ph.D., in a statement.
The second study, from a team at the University of California, San Francisco (UCSF), focused on the protein PD-L1, the target of some checkpoint-inhibiting drugs. Normally, checkpoint inhibitors work by recognizing PD-L1 on the surface of cancer cells and then interfering either with it or the related protein PD-1. The UCSF researchers discovered that in some patients, PD-L1 travels throughout the body, inhibiting immune cells before they can reach the cancer.
In those patients, the PD-L1 ends up in exosomes, which are vesicles that come from cancer cells and travel in the bloodstream to the lymph nodes, the UCSF team discovered. While there, they “disarm” the immune cells, so they’re unable to launch an attack against the cancer. They published their findings in the journal Cell.
The prevailing view of why patients sometimes don’t respond to PD-L1 inhibitors is that their cancers are not making enough of the protein. But the UCSF researchers showed “the protein was in fact being made at some point, and that it wasn’t being degraded,” senior author Robert Blelloch, M.D,. Ph.D., professor of urology at UCSF, said in a statement. “That’s when we looked at exosomes and found the missing PD-L1.”
In a second experiment, the UCSF team used the gene-editing technology CRISPR to delete two genes necessary for exosome production from cancer cells. Mice that received those cells had more activated immune cells in their lymph nodes than did animals that got unedited cancer cells.
They then treated a mouse model of colorectal cancer with a combination of a PD-L1 inhibitor and a drug that prevents exosomes from forming. Those mice survived longer than animals treated with either drug alone did.
Blelloch’s team plans to conduct further studies, with the ultimate goal of developing a “tumor cell vaccine” to help patients who don’t currently respond to checkpoint inhibitors.
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