EUSA Pharma, Inc.

Children with narcolepsy cannot choose when to wake or sleep. Image credit: Shutterstock/Roman Samborskyi. Paediatric patients with narcolepsy will now have access to Avadel’s Lumryz (sodium oxybate) after the US Food and Drug Administration (FDA) approved a supplemental new drug application. The expanded approval for the oral suspension is for the treatment of sudden muscle weakness, called cataplexy, or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy, as per a 17 October press release. Lumryz, which was approved in adults in the US in May last year, was also granted seven years of orphan drug exclusivity. This means the FDA will not approve another marketing application for a competing product until October 2031. Narcolepsy is a chronic neurological disorder that impacts the brain’s ability to regulate sleep and wake cycles, meaning people cannot choose when to wake or sleep. EDS and cataplexy are common symptoms in those with the disorder, with the latter occurring in 70% of patients. Whilst narcolepsy itself does not cause serious health problems; it has a significant impact on day-to-day life. It is thought Lumryz works by binding to gamma-aminobutyric acid B receptors in noradrenergic and dopaminergic neurons, increasing the time a person spends in deeper sleep. The treatment has a boxed warning as a central nervous system depressant, and for its potential for abuse and misuse. See Also: FDA approves AbbVie’s VYALEV for advanced Parkinson’s treatment Glaukos eyes FDA approval for ocular therapy after Phase III win The widened use of Lumryz intensifies the competition with Jazz Pharmaceutical’s rival compounds Xyrem (sodium oxybate) and blockbuster Xywav, a mixture of calcium, magnesium, potassium, and sodium oxybates. Unlike Lumryz, Jazz’s twice-nightly drugs require patients to wake up in the middle of sleep to take the second dose. The FDA highlighted this when granting the exclusive market period to Lumryz, ruling it was superior to Xyrem and Xywav due to the dosing regimen, according to Avadel. Avadel’s CEO Greg Divis said the approval is important for younger narcolepsy patients and their caregivers who “face significant challenges associated with waking up in the middle of the night to complete treatment regimens”. “With this label expansion, paediatric patients seven years and older living with narcolepsy now have the same option that adult patients with narcolepsy have – to choose a once-nightly treatment option that does not disrupt sleep for a middle of the night dose,” he added. Xyrem saw peak sales in 2020, bringing in annual revenue of $1.7bn. Xyrem sales decreased after the approval of Xywav, with the latter having more flexible dosing. Xywav passed the $1bn revenue mark last year and is forecast to generate more than $1.8bn by 2030, according to GlobalData’s Pharma Intelligence Centre. Lumryz is forecast to make $639m in the same year. GlobalData is the parent company of Pharmaceutical Technology . Jazz Pharmaceuticals has initiated multidistrict patent infringement lawsuits against Avadel over the past few years to block Lumryz’s entry to market, in addition to suing the FDA itself. A jury from the United States District Court for the District of Delaware gave its verdict in March this year, siding with Avadel for one patent whilst ruling against the company in relation to another. Avadel said it would appeal the decision and added legal proceedings would not impact the ongoing commercial launch of Lumryz, as per a statement at the time. Jazz was in court another time this year relating to a separate matter of misleading promotion relating to Xyrem. The company agreed to pay $20m in civil and criminal penalties over a period of five years.

Early results from a small study have convinced Centessa Pharmaceuticals to rapidly advance an experimental drug it believes could be a useful treatment for diseases hallmarked by excessive sleepiness.The study enrolled healthy volunteers who hadnt gotten enough sleep for a short period of time. It then assessed three doses of Centessas drug, one of which was only evaluated for safety.According to Centessa, the two tested doses significantly increased the amount of time it took for participants to go from fully awake to asleep, compared to placebo.The London-based biotechnology company now intends to start, before the end of the year, mid-stage studies that will evaluate its drug against the two main types of narcolepsy as well as an uncommon sleep disorder known as idiopathic hypersomnia.The smaller study set a high bar for the drug, and the data generated thus far has exceeded our expectations, giving us the confidence to accelerate the program into the next stage of clinical development earlier than anticipated, said Saurabh Saha, Centessas CEO, in a statement.Centessas share price was up 8% at markets open Tuesday. It rose higher, to a gain of more than 15%, before sliding back down in late morning trading.David Risinger, an analyst at the investment firm Leerink Partners, called the data highly compelling and the best so far from a new class of drugs aimed at sleepiness. The class targets orexin proteins, which regulate sleep and wakefulness, and has gotten buy-in from a growing list of developers that includes Takeda Pharmaceutical, Johnson & Johnson, Jazz Pharmaceutical and Alkermes.Early this year, Takeda said it would quickly begin late-stage testing of its orexin drug after scoring positive results from a clinical trial focused on Type 1 narcolepsy a condition that, in addition to sleep problems, also involves a sudden loss of muscle control.To Risinger, the data released Tuesday suggest that Centessas drug could ultimately be given as a 1 milligram, once-daily treatment, which would compare favorably to Takedas candidate. That drug has been evaluated at once- and twice-daily doses, up to 7 milligrams a day. Centessas results also imply that its drug is absorbed by the body faster than Takedas, according to Risinger.Centessas derived its data from Maintenance of Wakefulness Tests, a long-running tool used in sleep studies. The tests have participants sit in a dark, quiet room, on a bed with their back and neck supported by pillows. Sensors are attached to the head and face of the participant, who is then asked to look straight ahead and try not to fall asleep. One round of the test lasts no longer than 40 minutes, and is repeated approximately every two hours for several sessions.In Centessas study, dosing occurred at 11 p.m. and four total sessions were conducted. In the lowest, 1 mg arm, the average time it took to fall asleep was 18 minutes for drug-treated participants and 10 minutes for those on placebo. In the highest, 2.5 mg arm, the times were 32 minutes and 17 minutes, respectively which, Centessa said, shows that the dose restored normative wakefulness.The company also classified the safety and tolerability of its drug as favorable. All adverse events related to treatment were mild and transient, and none led to any participant dropping out of the study. Researchers also havent observed adverse events associated with other orexin drugs that work like Centessas, such as frequent urination or needing to urinate, insomnia, blood pressure increases or increased saliva production. '

Sanofi's flu vaccine manufacturing hiccup in China, DualityBio's proposed Hong Kong IPO and UCB's $680 million sale of some Chinese assets made our news this week. Sanofi has suspended distribution of its two flu vaccines in China out of concern of waning potency. BioNTech's antibody-drug conjugate partner, DualityBio, has filed for a Hong Kong IPO. UCB will offload some Chinese assets for $680 million. And more.1. Sanofi halts flu vaccine distribution in China over fear of declining potencySanofi has temporarily stopped selling its two flu vaccines, Vaxigrip and VaxigripTetra, in China after a routine quality follow-up test flagged a decline in the vaccines’ potency in doses that were not yet distributed. The company attributed the problem to “unexpected circumstances” at the company’s production line in Shenzhen, China, which supplies doses only for the Chinese market.2. Duality plans Hong Kong IPO to fund trials of BioNTech-partnered ADCs and beyondChina’s Duality Biotherapeutics has filed for a Hong Kong IPO. The antibody-drug conjugate specialist set up shop in 2019 and has attracted deals with BioNTech, BeiGene and Adcendo that could be worth more than $4 billion combined. Duality named BioNTech-partnered ADCs targeting HER2 and B7-H3 as its “core products,” with the HER2 program nearing a potential application for accelerated approval in 2025.3. UCB sells off production plant and a clutch of older meds in China for $680MAnother foreign company is trimming its business in China. UCB is selling off its mature neurology and allergy brands in mainland China, plus a manufacturing site in the Chinese city of Zhuhai, to investment shops CBC Group and Mubadala for $680 million. The Belgian company will instead explore the launch of novel medicines in immunology, neurology and rare diseases in China, UCB CEO Jean-Christophe Tellier said.4. FDA weighs limiting PD-1 drugs in stomach cancer, calls on experts to discuss Merck, BMS and BeiGene medsThe FDA will hold an advisory committee meeting to discuss whether approvals for PD-1 inhibitors in advanced gastric and gastroesophageal junction adenocarcinoma and esophageal squamous cell carcinoma should be restricted based on tumors’ PD-L1 expression. BeiGene’s two open applications for Tevimbra, plus existing approvals for Merck’s Keytruda and Bristol Myers Squibb’s Opdivo, will be examined closely.5. As sales climb, Jazz's Epidiolex falls short in Japanese study in treatment-resistant epilepsiesA phase 3 Japanese study of Jazz Pharma’s cannabinoid drug Epidiolex has failed on the primary endpoint measuring seizure frequency in certain patients with treatment-resistant epilepsies. Still, the company pointed to numeric improvements across primary and secondary endpoints, as well as the drug’s overall global data, saying it plans to speak with Japanese authorities about a potential filing.6. Ipsen sues CSPC Pharma to block rival to cancer drug Onivyde (Bloomberg Law)Ipsen has filed a patent infringement lawsuit against China’s CSPC Pharma. The lawsuit centers on Ipsen’s Onivyde, a liposome formulation of the chemotherapy irinotecan, and CSPC’s irinotecan liposome candidate, which was filed with the FDA in late 2023 for previously treated pancreatic cancer. Ipsen alleges that CSPC steps on its new patent, which was issued Aug. 13, according to the complaint (PDF).Other News of Note:7. Bora's expansion tear continues as CDMO takes up stake in Tanvex, gains manufacturing capabilities8. With new focus, Kyowa Kirin pulls decades-old breast cancer drug Fareston from US market9. Bharat Biotech to launch oral cholera vaccine developed in partnership with Hilleman Labs (release)10. Tech company Fujitsu partners with Paradigm Health to boost clinical trials in Japan11. YolTech sells China rights to cholesterol gene editing therapy to Salubris for $29M12. API maker Global Calcium stung with Form 483 filing after FDA inspection of Indian plant