The Biden administration last week appealed a 2023 jury decision , which found that Gilead did not infringe on key government patents in its HIV prevention regimen consisting of the drugs Truvada (emtricitabine/tenofovir disoproxil fumarate) and Descovy (emtricitabine/tenofovir alafenamide).
In May 2023, a Delaware jury overwhelmingly took Gilead’s side, noting that the U.S. government did not have enough evidence to establish that using the HIV drugs violated three key patents.
The jury also unanimously agreed with the pharma that these patents were invalid in the first place, in part because the technologies they protect were obvious to professionals knowledgeable in the space.
In March 2024, a Delaware court gave the government some breathing room when it granted the state’s motion to “upset the jury’s findings” of direct infringement and the invalidity of these patents. In particular, the court ruled against the jury’s verdict that the patents were not infringed but upheld the view that the patents were invalid.
The government’s appeal last week—filed by the Department of Justice for the Department of Health and Human Services—seeks to reverse the previous rulings on the invalidity of their patent claims over Truvada and Descovy.
First approved in 2004 for the treatment of HIV, Truvada is a combination of two drugs—emtricitabine, a nucleoside reverse transcriptase inhibitor, and a prodrug of tenofovir, which is a nucleotide reverse transcriptase inhibitor. Both of its active ingredients allow Truvada to prevent the HIV virus from infecting a cell and embedding its genetic material into the host’s DNA.
In July 2012, the FDA signed off on the preventative use of Truvada, allowing its administration to reduce the risk of sexually acquired HIV.
Descovy is a newer generation drug that the FDA approved for HIV prevention in October 2019. It also uses emtricitabine, but combines it with tenofovir alafenamide, another tenofovir prodrug.
In November 2019, the Trump administration sued Gilead over the use of Truvada and Descovy, alleging that the combination regimen was first invented by scientists at the Centers for Disease Control and Prevnetion in the early 2000s.
“To date, the government has spent hundreds of millions of dollars on clinical studies of these treatment regimens,” the Justice Department wrote in its announcement at the time, adding that Gilead “has repeatedly refused to obtain a license for use of the patented drug regimens, while continuing to profit from hundreds of millions of dollars of publicly funded research.”
Eli Lilly’s Mounjaro (tirzepatide) is able to elicit greater weight loss in overweight or obese patients than Novo Nordisk’s Ozempic (semaglutide), according to the results of a new observational study.
The findings, published Monday in JAMA Internal Medicine, showed that patients on Mounjaro lost 2.4% more body weight at three months, compared with those taking Ozempic. Lilly’s GLP-1 treatment widened its lead through six and 12 months of treatment, leading to 4.3% and 6.9% greater weight loss than Ozempic, respectively.
According to researchers, patients treated with Mounjaro also had significantly better chances of seeing meaningful weight loss than those on Ozempic. In the study, those taking Lilly’s obesity drug were 76% more likely to achieve weight loss of at least 5% and more than three times as likely to drop 15% of their body weight or more.
Both therapies had similar safety profiles with no significant differences in the risk of gastrointestinal adverse events between those receiving tirzepatide and semaglutide, according to the study. However, discontinuations in the study were common with more than 50% of patients taking either drug stopping treatment. It is not clear whether the discontinuations were due to side effects or other reasons.
“To our knowledge, this study represents the first clinical comparative effectiveness study of tirzepatide and semaglutide in adults with overweight or obesity,” the researchers wrote, noting that the while findings demonstrate weight loss of 5% or greater with both therapies, “the benefit was greater with tirzepatide.”
Monday’s results mirror the findings of a prior real-world analysis from healthcare data and analytics firm Truveta, which showed that Mounjaro was three times as likely to elicit 15% weight loss than Ozempic.
Still, the researchers cautioned that their findings have limitations, chief of which is the observational design of the study.
Rather than pitting Mounjaro and Ozempic against each other in a controlled, head-to-head clinical trial, Monday’s study drew from electronic health records of patients who had received either drug. This approach could have introduced unmeasured bias and uncertainties into the analysis, according to the researchers. Additional studies are needed to better understand the comparative efficacies of these GLP-1 therapies, they contend.
Lilly and Novo, currently the leaders in the obesity market, are running their own head-to-head studies. In April 2023, Lilly launched its Phase IIIb SURMOUNT-5 trial, which will directly compare the efficacy of tirzepatide to semaglutide in overweight or obese adults without type 2 diabetes. The results of the study are expected in November 2024.
In November 2023, Novo kicked off its own head-to-head study, targeting Lilly’s Zepbound (tirzepatide) with its next-generation investigational weight-loss therapy CagriSema. This study is expected to wrap up in the latter half of 2025.
About a third of people with Parkinson's disease reported cognitive symptoms early in the disease course, a large cross-sectional study showed.
Of 25,000 Fox Insight study participants who had a Parkinson's diagnosis for a median of 3 years, 32% reported at least one cognitive symptom at baseline, reported Jennifer Purks, MD, of the University of Rochester in New York, and co-authors.
The most commonly reported cognitive symptoms involved memory (13%), language or word finding (12%), and concentration or attention (9%), Purks and colleagues wrote in Neurology Clinical Practice.
Cognitive symptoms were reported by 29% of patients in the first year after diagnosis, by 32% in the next few years, and by 35% of patients within 8 to 9 years of diagnosis. These symptoms were predicted by depression (adjusted OR 1.5), worse motor activity scores (OR 1.4 per 10-point increment on a 52-point scale), and higher education (OR 1.2 per year).
In the online Fox Insight study, Parkinson's patients were asked to report their most bothersome problems in their own words by answering open-ended questions in the Parkinson Disease Patient Report of Problems (PD-PROP). The researchers used human curation, natural language processing, and machine learning to develop an algorithm to convert verbatim responses to classified symptoms.
Subjective cognitive concerns are common in Parkinson's disease. They don't always align with objective findings, although a recent Fox Insight study suggested that an estimated 45% of Parkinson's patients with self-reported cognitive concerns developed new-onset cognition-related functional impairment over 3 years.
"Subjective cognitive complaints may be an early indicator of future decline in cognitive abilities and functional impairment, even when there is currently no evidence of cognitive decline on formal cognitive testing," observed co-author Daniel Weintraub, MD, of the University of Pennsylvania School of Medicine in Philadelphia.
"Overall, there is alignment between self-reported cognitive decline and objective cognitive assessments, but given how cognitive test norming is done, some high-functioning patients may notice cognitive changes in themselves but test normally," Weintraub told MedPage Today.
The large sample size of the Fox Insight study, combined with unconstrained free text reporting, allowed the identification of a broader spectrum of bothersome cognitive problems in Parkinson's than was previously possible, Purks and co-authors pointed out.
"The cognitive concerns begin early after diagnosis and have a parallel association with motor functional impairment and depression," they noted. "The association of depression with reporting cognitive problems as a most bothersome problem for all domains except visual spatial symptoms demonstrates the importance of mood screening and treatment strategies targeted to the underlying source of the subjective cognitive concerns."
Purks and colleagues studied data from 25,192 participants in the ongoing Fox Insight study who had a median age of 67. Every 3 months, Parkinson's patients were asked to respond to the PD-PROP. For people with more than one PD-PROP, only the first report was used.
The researchers also evaluated age, sex, years since diagnosis, and scores on the Movement Disorder Society Unified Parkinson Disease Rating Scale Part II (MDS-UPDRS Part II) and the Geriatric Depression Scale-15 (GDS-15) using Fox Insight data.
The MDS-UPDRS Part II measures motor experiences of daily living; scores range from 0 to 52, with increasing scores indicating greater disability. The maximum interval between PD-PROP data and MDS-UPDRS scores was 90 days. The GDS-15 ranges from 0 to 15, with higher scores indicating more depressive symptoms. Depression was defined by GDS-15 scores of 5 or greater.
A total of 8,001 people reported any cognitive symptom at baseline. Depression was significantly associated with cognitive problems in all domains except visuospatial abilities.
Among Parkinson's patients with at least one cognitive symptom, 17% reported posterior cortical-related symptoms (visuospatial, memory, or language), 7% reported frontostriatal-related symptoms (executive abilities, concentration, or attention), and 14.3% reported both. The odds of posterior cortical symptoms versus frontostriatal symptoms increased with age and MDS-UPDRS part II scores, but not with depression.
The study had several limitations, the researchers acknowledged. Some patient reports were ambiguous, and misinterpretation or misclassification was possible. Some cognitive categories were broad; more granular classification may have provided additional insights, such as distinguishing language comprehension and expression problems. The online nature of the study also may have led to potential volunteer bias.
Disclosures
This study was supported by the Michael J. Fox Foundation.
Purks reported no disclosures. Several co-authors are employees of Grey Matter Technologies.
Primary Source
Neurology Clinical Practice
Source Reference: Purks JL, et al "Cognitive symptoms in cross-sectional Parkinson disease cohort evaluated by human-in-the-loop machine learning and natural language processing" Neurol Clin Pract 2024; DOI: 10.1212/CPJ.0000000000200334.
https://www.medpagetoday.com/neurology/parkinsonsdisease/111001
The ranibizumab ocular implant (Susvimo) for neovascular (wet) age-related macular degeneration (nAMD) will return to the U.S. market "in the coming weeks," Genentech announced.
The return follows a nearly 2-year hiatus resulting from a voluntary recall initiated after test results showed that "some implants did not perform to Genentech's standards." Specifically, the performance issue involved septum dislodgement, which according to the device's prescribing information, would interfere with normal functioning.
In announcing FDA approval of the reintroduction, company officials said updates to the device and refill syringe, as well as improvements in the manufacturing process, restored the device's function to expected standards.
"We are pleased to reintroduce Susvimo, a unique therapeutic approach shown to provide an effective alternative to regular eye injections by preserving vision with two refills per year in phase III study of patients with wet AMD," said Levi Garraway, MD, PhD, Genentech's chief medical officer, in a company statement. "Susvimo's return to the retina community reflects our unwavering commitment to provide innovative retinal treatments, and lays the groundwork for future advancements."
Prior to the recall, clinical trials showed similar vision outcomes between the ranibizumab implant, with refills every 6 months, and monthly intravitreal injections of the anti-VEGF agent. Assessment of patient-reported outcomes showed that patients overwhelmingly preferred the device and its reduced treatment burden over conventional injections. Studies ongoing at the time of the recall showed similar long-term outcomes compared with monthly intravitreal anti-VEGF injections.
The FDA approved the device in late 2021, about a year before the voluntary recall.
https://www.medpagetoday.com/ophthalmology/generalophthalmology/111004
Extended-release 7-day injectable buprenorphine was safe and tolerable for most patients who had minimal-to-mild opioid withdrawal, a nonrandomized trial found.
Among 100 adult patients with minimal-to-mild opioid withdrawal scores who were given a 24-mg dose of extended-release buprenorphine, only 10 people (10%, 95% CI 4.9%-17.6%) saw a 5-point or greater jump in withdrawal symptoms within 4 hours of injection, reported Gail D'Onofrio, MD, of the Yale School of Medicine in New Haven, Connecticut, and colleagues.
Scores were determined using the Clinical Opiate Withdrawal Scale (COWS), an 11-item questionnaire that assesses opioid withdrawal levels based on resting pulse rate, sweating, gastrointestinal upset, and other symptoms. A higher score indicates a greater degree of withdrawal. A COWS score of 0 to 7 represents minimal-to-mild withdrawal. Patients who saw benefit with the extended-release agent had COWS scores 4 to 7.
The researchers also reported in JAMA Network Open that of those 10 patients, 7% (95% CI 2.9%-13.9%) saw symptoms escalate to moderate or greater withdrawal within 4 hours, while 2% (95% CI 0.2%-7.0%) experienced "precipitated withdrawal" within 1 hour of injection. Precipitated withdrawal is akin to the experience of receiving naloxone (Narcan) and can involve vomiting, diarrhea, and other unpleasant side effects, D'Onofrio explained to MedPage Today.
Overall, seven patients (7%, 95% CI 2.9%-13.9%) went through precipitated withdrawal within 4 hours of injection, including two of 63 participants (3.2%) with a COWS score of 4 to 7 and five of 37 participants (13.5%) with a COWS score of 0 to 3.
The study examined whether patients with untreated opioid use disorder (OUD) and minimal-to-mild withdrawal could tolerate a 7-day dose of buprenorphine. Patients with OUD typically aren't treated with medication until they are in significant withdrawal, due to fear of precipitated withdrawal. For that reason, "[n]o one has ever even attempted to give buprenorphine in that [0 to 7] range," D'Onofrio said.
Few people with a COWS score of 4 or more experienced precipitated withdrawal in the study, suggesting "it would be very reasonable and safe to use our 7-day injectable" in that population, she noted.
"And it's 7 days," D'Onofrio said, "so that's even better [than sublingual buprenorphine] because you have 7 days to make people feel better and not have to internally decide 'Am I going to take my medicine today or not?'"
However, the roughly 13% incidence of precipitated withdrawal in the 0 to 3 COWS group indicated those patients are not candidates for extended-release buprenorphine, she clarified.
Still, "this is a real game-changer for emergency physicians and clinicians, even in the clinic, who would be able to induce people on buprenorphine much earlier than they previously could have," D'Onofrio said.
The trial was conducted in four emergency departments. Mean patient age was 36.5 years, and most were male. About half of study participants were white (51%); 35% were Black or African American, and 13% were Hispanic or Latino.
Just under half (48%) reported unstable housing in the last 12 months and 36% currently had unstable housing. Most patients had public insurance and tested positive for fentanyl.
Outcomes were measured daily for 7 days using telephone surveys and in person on day 7. Recruitment took place from 2020 to 2023.
Participants were given gift cards as compensation with a maximum value of $200. They were referred to community-based programs or clinicians for ongoing OUD treatment.
Site pain scores were low immediately after injection and after 4 hours. On any of the 7 days, between 33% and 43% of patients who responded to surveys reported no cravings, and between 78% and 85% reported no use of opioids. Overall, 60% of patients reported no days of opioid use. Most patients (73%) were still engaged in treatment on day 7.
With traditional sublingual buprenorphine, "it takes days to get a steady state and people are still going to crave, and when they're craving, they're going to use opioids," D'Onofrio said. In contrast, the extended-release formulation takes several hours to reach "a good point ... and it will stay up for a long time ... so you're not getting peaks and troughs," she stated.
Five serious adverse events (AEs) occurred that required hospitalization; two were associated with treatment.
Limitations included a lack of a control group and the study's small size and strict eligibility criteria. The researchers had some discretion in selecting patients with COWS score of 0 to 3, which may have led to selection bias.
Disclosures
The study was supported by the Clinical Coordinating Center and the Data and Statistics Center of the Emmes Company-Department of Health and Human Services/National Institute on Drug Abuse (NIDA). Braeburn Pharmaceuticals provided CAM2038 free of charge for use in this trial via NIDA.
D'Onofrio disclosed support from the NIH-Helping to End Addiction Long-Term Initiative.
Co-authors disclosed support from, and/or relationships with, the NIH-Helping to End Addiction Long-Term Initiative, the Foundation for Opioid Response Efforts (FORE), the Emergency Medicine Foundation, NIDA, the NIH, Braeburn Pharmaceuticals, Berkshire Biomedical, Titan, Journey Colab, Opiant Pharmaceuticals, Cervel Therapeutics, Lundbeck, AstraZeneca, Pocket Naloxone, and Kinoxis. A co-author disclosed having a patent for Tradipitant with the University of Kentucky and Vanda Pharmaceuticals.
Primary Source
JAMA Network Open
Source Reference: D'Onofrio G, et al "Extended-release 7-day injectable buprenorphine for patients with minimal to mild opioid withdrawal" JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.20702.
https://www.medpagetoday.com/publichealthpolicy/opioids/111005
Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM) today announced that the European Commission has granted marketing authorization for LIVMARLI® (maralixibat) oral solution for the treatment of progressive familial intrahepatic cholestasis (PFIC) in patients three months of age and older. The approval follows a positive opinion by the CHMP which concluded that LIVMARLI in PFIC brings significant clinical benefit based on improved efficacy and a major contribution to patient care compared to the existing approved treatment for PFIC. Further, evaluation by COMP recommended maintenance of Orphan Drug Designation for LIVMARLI in PFIC.
