Latest news with #MichaelHorowitz
The Age
4 days ago
- Health
- The Age
Ozempic in a pill? The next generation of weight-loss drugs emerges
'The development of GLP-1 and incretin-based drugs has revolutionised the space. It has carved out the biggest class of drugs ever. And it has the power to truly revolutionise our health-span,' said Associate Professor Garron Dodd, head of the Metabolic Neuroscience Research Laboratory at the University of Melbourne and founder of Gallant Bio, which is developing its own obesity drugs. 'It's a glorious dawn, but it's just the start.' Weight loss in a pill Much as our eyes and ears sense the world and send data to our brains, our digestive tracts need ways of sending back data on what they are eating, and how much. They do this, in part, by secreting various chemical signals – hormones. Glucagon-like peptide-1 is secreted by the intestines and triggers the pancreas to produce insulin. The first GLP-1 drugs took advantage of this to become powerful treatments for diabetes. But GLP-1 has much wider effects beyond blood-sugar control. Receptors for the hormone spread throughout the body, even in the brain, where they trigger a feeling of fullness and decrease appetite. A once-weekly dose of semaglutide, plus lifestyle changes, led volunteers in a phase 3 trial to lose 14.9 per cent of their body weight over 15 months. GLP-1 drugs like Wegovy essentially copy that human hormone. That makes them fragile. They need to be kept refrigerated, and injected subcutaneously rather than taken by mouth – as the stomach's acid would quickly break them down. An oral version of semaglutide has been developed, but only 1 per cent of the drug actually makes its way to the target receptors, and it appears less effective than the injectable version for weight loss. Loading Researchers at Japan's Chugai Pharmaceutical Co figured out a way around this problem. They designed a small molecule that can bind to the same receptor as GLP-1 and trigger it. It mimics the effect without mimicking the structure. 'It's a development I never would have thought feasible,' said Professor Michael Horowitz, a University of Adelaide researcher who authored a commentary on the drug in the Lancet. Chugai licensed the molecule to US-based Eli Lilly in 2018. Last week, the company reported participants on the highest dose in a clinical trial lost 7.9 per cent of their body weight over 40 weeks. The full details of the trial have not yet been reported, and whether the weight loss is maintained over the longer term is unclear. More than a quarter of patients reported diarrhoea, 16 per cent nausea and 14 per cent vomiting. The preliminary results are 'close enough to broadly call it similar' to semaglutide, said Professor Jonathan Shaw, who led the Australian arm of Lilly's trial at the Baker Heart and Diabetes Institute in Melbourne. 'I don't think we can confidently say it's better or worse. It's definitely in the same ballpark.' It's also not known if the drug will offer the range of other benefits that GLP-1 inhibitors provide in addition to weight loss, like reductions in cardiovascular disease and Alzheimer's risk (and maybe even addictive behaviours). Horowitz said the efficacy data was promising, but he wanted to see more information about adverse effects, which he said were understated generally across semaglutide trials because they relied on patients to report their own side effects. 'It hasn't served the interests of pharma to quantify how well this is tolerated.' Pfizer was developing a similar once-daily GLP-1 pill but cancelled the program in April after a patient in a clinical trial suffered liver damage. A pill should, theoretically, be cheaper and easier to make than an injector – Novo Nordisk, maker of Wegovy and its diabetes drug antecedent Ozempic, has struggled to keep up with demand for semaglutide – and dramatically easier to transport. At present, the drug must be kept refrigerated right from European factories to a patient's home. 'That all adds to the cost,' said Shaw. There could also be cost benefits from increased competition as more drugs are approved – possibly pushing the price down far enough for governments to consider subsidising it. Lilly expects to apply for regulatory approval for the drug later this year. While orforglipron has attracted the most excitement – Eli Lilly's shares have surged since they announced the trial results – it is just one of several new drugs in late-stage development. These drugs might be of particular value to 15 per cent or so of people whose bodies do not seem to respond to semaglutide. And people don't seem to stay on the injectable drugs – less than half are still using them a year later, per a study 2024 study – despite the fact weight rebound is likely if you stop using them. 'Is it the injection? Is it the cost? Or is it due to adverse effects? We don't know,' said Horowitz. The new drugs might also offer weight-loss benefits. Mounjaro, for example, mimics both GLP-1 and the gastric inhibitory polypeptide, which increases metabolism and appears to lead to better weight-loss results. The new drugs, like Lilly's retatrutide, target even more receptors, with the hope of even greater effects. It's all good news for Rochelle McDonald. She does not mind taking a weekly injection – 'the stabby-stab' – now she's found ways of coping with the side effects. But paying $240 a month for her current dose of the medicine is 'a commitment in itself'. 'I think a daily pill would be good,' she said. 'If it comes in at a good price point.'
Sydney Morning Herald
4 days ago
- Health
- Sydney Morning Herald
Ozempic in a pill? The next generation of weight-loss drugs emerges
'The development of GLP-1 and incretin-based drugs has revolutionised the space. It has carved out the biggest class of drugs ever. And it has the power to truly revolutionise our health-span,' said Associate Professor Garron Dodd, head of the Metabolic Neuroscience Research Laboratory at the University of Melbourne and founder of Gallant Bio, which is developing its own obesity drugs. 'It's a glorious dawn, but it's just the start.' Weight loss in a pill Much as our eyes and ears sense the world and send data to our brains, our digestive tracts need ways of sending back data on what they are eating, and how much. They do this, in part, by secreting various chemical signals – hormones. Glucagon-like peptide-1 is secreted by the intestines and triggers the pancreas to produce insulin. The first GLP-1 drugs took advantage of this to become powerful treatments for diabetes. But GLP-1 has much wider effects beyond blood-sugar control. Receptors for the hormone spread throughout the body, even in the brain, where they trigger a feeling of fullness and decrease appetite. A once-weekly dose of semaglutide, plus lifestyle changes, led volunteers in a phase 3 trial to lose 14.9 per cent of their body weight over 15 months. GLP-1 drugs like Wegovy essentially copy that human hormone. That makes them fragile. They need to be kept refrigerated, and injected subcutaneously rather than taken by mouth – as the stomach's acid would quickly break them down. An oral version of semaglutide has been developed, but only 1 per cent of the drug actually makes its way to the target receptors, and it appears less effective than the injectable version for weight loss. Loading Researchers at Japan's Chugai Pharmaceutical Co figured out a way around this problem. They designed a small molecule that can bind to the same receptor as GLP-1 and trigger it. It mimics the effect without mimicking the structure. 'It's a development I never would have thought feasible,' said Professor Michael Horowitz, a University of Adelaide researcher who authored a commentary on the drug in the Lancet. Chugai licensed the molecule to US-based Eli Lilly in 2018. Last week, the company reported participants on the highest dose in a clinical trial lost 7.9 per cent of their body weight over 40 weeks. The full details of the trial have not yet been reported, and whether the weight loss is maintained over the longer term is unclear. More than a quarter of patients reported diarrhoea, 16 per cent nausea and 14 per cent vomiting. The preliminary results are 'close enough to broadly call it similar' to semaglutide, said Professor Jonathan Shaw, who led the Australian arm of Lilly's trial at the Baker Heart and Diabetes Institute in Melbourne. 'I don't think we can confidently say it's better or worse. It's definitely in the same ballpark.' It's also not known if the drug will offer the range of other benefits that GLP-1 inhibitors provide in addition to weight loss, like reductions in cardiovascular disease and Alzheimer's risk (and maybe even addictive behaviours). Horowitz said the efficacy data was promising, but he wanted to see more information about adverse effects, which he said were understated generally across semaglutide trials because they relied on patients to report their own side effects. 'It hasn't served the interests of pharma to quantify how well this is tolerated.' Pfizer was developing a similar once-daily GLP-1 pill but cancelled the program in April after a patient in a clinical trial suffered liver damage. A pill should, theoretically, be cheaper and easier to make than an injector – Novo Nordisk, maker of Wegovy and its diabetes drug antecedent Ozempic, has struggled to keep up with demand for semaglutide – and dramatically easier to transport. At present, the drug must be kept refrigerated right from European factories to a patient's home. 'That all adds to the cost,' said Shaw. There could also be cost benefits from increased competition as more drugs are approved – possibly pushing the price down far enough for governments to consider subsidising it. Lilly expects to apply for regulatory approval for the drug later this year. While orforglipron has attracted the most excitement – Eli Lilly's shares have surged since they announced the trial results – it is just one of several new drugs in late-stage development. These drugs might be of particular value to 15 per cent or so of people whose bodies do not seem to respond to semaglutide. And people don't seem to stay on the injectable drugs – less than half are still using them a year later, per a study 2024 study – despite the fact weight rebound is likely if you stop using them. 'Is it the injection? Is it the cost? Or is it due to adverse effects? We don't know,' said Horowitz. The new drugs might also offer weight-loss benefits. Mounjaro, for example, mimics both GLP-1 and the gastric inhibitory polypeptide, which increases metabolism and appears to lead to better weight-loss results. The new drugs, like Lilly's retatrutide, target even more receptors, with the hope of even greater effects. It's all good news for Rochelle McDonald. She does not mind taking a weekly injection – 'the stabby-stab' – now she's found ways of coping with the side effects. But paying $240 a month for her current dose of the medicine is 'a commitment in itself'. 'I think a daily pill would be good,' she said. 'If it comes in at a good price point.'
Straits Times
15-06-2025
- Politics
- Straits Times
Israel's strikes on Iran were years in the making: Analysts
Fire of Israeli attack on Sharan Oil depot is seen following the Israeli strikes on Iran, in Tehran, on June 15. PHOTO: REUTERS Israel's strikes on Iran were years in the making: Analysts PARIS - Israel's unprecedented strikes on Iran, which have killed top military leaders and nuclear scientists, required years of meticulous intelligence gathering and infiltration, experts say. Israel said it hit hundreds of targets on June 13 alone, and has since continued its attacks, striking a defence facility and fuel depots on June 15 . The fiercest-ever exchange of fire between the arch foes came in the midst of ongoing talks between Tehran and Washington seeking to reach a deal on Iran's nuclear programme. 'Israel has been following the nuclear programme for 15 years,' Israeli analyst Michael Horowitz told AFP. 'The strikes we see are the result of years of intelligence gathering and infiltration of the Islamic republic.' Israel has previously carried out more limited attacks against Iranian military sites, including in October 2024. 'It seems that this week's operation had been in preparation for months, with an acceleration after the operation last year significantly weakened Iranian air defences,' Mr Horowitz said. The United States and other Western countries, along with Israel, accuse Iran of seeking a nuclear weapon. Tehran denies that, but has gradually broken away from its commitments under a 2015 nuclear deal it struck with world powers, which the United States withdrew from during President Donald Trump's first term. The landmark accord had provided Iran sanctions relief in exchange for curbs on its atomic programme. 'Impressive' precision Israel is long believed to have carried out sabotage operations inside Iran through its Mossad espionage agency, but the attacks that started on June 13 are by far the broadest in scope. The campaign has shown Israel to be capable of precisely locating and taking out high-ranking Iranian officials and nuclear scientists. A European security source said the strikes showed 'an impressive degree of precision and mastery'. Israel says it has killed 20 military and security targets, including the armed forces' chief of staff and the head of Iran's Revolutionary Guards, as well as nine nuclear scientists. Mr Danny Citrinowicz, of the Tel Aviv-based Institute for National Security Studies, said the ability to take out high-ranking officials showed 'intelligence, but also operational superiority of Israel over Iran'. 'It's highly connected to the ability to collect information, intelligence in Iran for years, excellent intelligence that actually allows you to detect where they're living, the seniors, also the nuclear scientists,' he told AFP. The latest targeted strikes come after Israel killed Ismail Haniyeh, the political leader of the Palestinian militant group Hamas, in a Tehran guesthouse in July 2024 . Haniyeh had been in town for the inauguration of Iranian President Masoud Pezeshkian, and was reportedly killed by an explosive device that Israeli operatives had placed in the guesthouse weeks before. Analysts at the time saw the attack as a major intelligence failure by Iran. But 'still Iran didn't learn and didn't have the ability to lock the holes in their system', said Mr Citrinowicz. Smuggled drone News site Axios reported that Mossad agents inside Iran helped prepare the J une 13 strikes, pre-positioning weapon systems near air defence targets, including by hiding them inside vehicles, and launching them when the attack started. An Israeli intelligence official told Axios that Mossad had 'established an attack drone base inside Iran with drones that were smuggled in long before the operation'. A former Israeli intelligence official told The Atlantic that 'Iranians opposed to the regime make for a ready recruiting pool', and that 'Iranians working for Israel were involved in efforts to build a drone base inside the country'. Mr Alain Chouet, the former number three in the French intelligence, said he was convinced Israel had 'half a dozen cells capable of acting at any moment' inside Iran. Iran regularly executes people it accuses of spying for Israel. It is unclear what role, if any, Israel's key military and diplomatic ally the United States had in the latest strikes. Before the attack early on June 13 , Mr Trump publicly urged Israel to allow time for diplomacy, as a sixth round of US-Iranian nuclear talks were set to be held in Oman at the weekend. The US president on June 15 said Washington 'had nothing to do' with ally Israel's campaign. But Iran's Foreign Minister Abbas Araghchi on June 15 said Tehran had 'solid proof of the support of the American forces and American bases in the region' for the attacks. And Israel's Prime Minister Benjamin Netanyahu said on June 14 his country was acting with 'the clear support of the president of the United States'. AFP Join ST's Telegram channel and get the latest breaking news delivered to you.
Yahoo
15-06-2025
- Politics
- Yahoo
Israel's strikes on Iran were years in the making: analysts
Israel's unprecedented strikes on Iran, which have killed top military leaders and nuclear scientists, required years of meticulous intelligence gathering and infiltration, experts say. Israel said it hit hundreds of targets on Friday alone, and has since continued its attacks, striking a defence facility and fuel depots on Sunday. The fiercest-ever exchange of fire between the arch foes came in the midst of ongoing talks between Tehran and Washington seeking to reach a deal on Iran's nuclear programme. "Israel has been following the nuclear programme for 15 years," Israeli analyst Michael Horowitz told AFP. "The strikes we see are the result of years of intelligence gathering and infiltration of the Islamic republic." Israel has previously carried out more limited attacks against Iranian military sites, including in October last year. "It seems that this week's operation had been in preparation for months, with an acceleration after the operation last year significantly weakened Iranian air defences," Horowitz said. The United States and other Western countries, along with Israel, accuse Iran of seeking a nuclear weapon. Tehran denies that, but has gradually broken away from its commitments under a 2015 nuclear deal it struck with world powers, which the United States withdrew from during President Donald Trump's first term. The landmark accord had provided Iran sanctions relief in exchange for curbs on its atomic programme. - 'Impressive' precision - Israel is long believed to have carried out sabotage operations inside Iran through its Mossad espionage agency, but the attacks that started on Friday are by far the broadest in scope. The campaign has shown Israel to be capable of precisely locating and taking out high-ranking Iranian officials and nuclear scientists. A European security source said the strikes showed "an impressive degree of precision and mastery". Israel says it has killed 20 military and security targets, including the armed forces' chief of staff and the head of Iran's Revolutionary Guards, as well as nine nuclear scientists. Danny Citrinowicz, of the Tel Aviv-based Institute for National Security Studies, said the ability to take out high-ranking officials showed "intelligence, but also operational superiority of Israel over Iran". "It's highly connected to the ability to collect information, intelligence in Iran for years, excellent intelligence that actually allows you to detect where they're living, the seniors, also the nuclear scientists," he told AFP. The latest targeted strikes come after Israel killed Ismail Haniyeh, the political leader of the Palestinian militant group Hamas, in a Tehran guesthouse in July last year. Haniyeh had been in town for the inauguration of Iranian President Masoud Pezeshkian, and was reportedly killed by an explosive device that Israeli operatives had placed in the guesthouse weeks before. Analysts at the time saw the attack as a major intelligence failure by Iran. But "still Iran didn't learn and didn't have the ability to lock the holes in their system", said Citrinowicz. - Smuggled drones - News site Axios reported that Mossad agents inside Iran helped prepare Friday's strikes, pre-positioning weapon systems near air defence targets, including by hiding them inside vehicles, and launching them when the attack started. An Israeli intelligence official told Axios that Mossad had "established an attack drone base inside Iran with drones that were smuggled in long before the operation". A former Israeli intelligence official told The Atlantic that "Iranians opposed to the regime make for a ready recruiting pool", and that "Iranians working for Israel were involved in efforts to build a drone base inside the country". Alain Chouet, the former number three in the French intelligence, said he was convinced Israel had "half a dozen cells capable of acting at any moment" inside Iran. Iran regularly executes people it accuses of spying for Israel. It is unclear what role, if any, Israel's key military and diplomatic ally the United States had in the latest strikes. Before the attack early on Friday, Trump publicly urged Israel to allow time for diplomacy, as a sixth round of US-Iranian nuclear talks were set to be held in Oman at the weekend. The US president on Sunday said Washington "had nothing to do" with ally Israel's campaign. But Iran's Foreign Minister Abbas Araghchi on Sunday said Tehran had "solid proof of the support of the American forces and American bases in the region" for the attacks. And Israel's Prime Minister Benjamin Netanyahu said on Saturday his country was acting with "the clear support of the president of the United States". bur-dla/ah/smw
France 24
15-06-2025
- Politics
- France 24
Israel's strikes on Iran were years in the making: analysts
Israel said it hit hundreds of targets on Friday alone, and has since continued its attacks, striking a defence facility and fuel depots on Sunday. The fiercest-ever exchange of fire between the arch foes came in the midst of ongoing talks between Tehran and Washington seeking to reach a deal on Iran's nuclear programme. "Israel has been following the nuclear programme for 15 years," Israeli analyst Michael Horowitz told AFP. "The strikes we see are the result of years of intelligence gathering and infiltration of the Islamic republic." Israel has previously carried out more limited attacks against Iranian military sites, including in October last year. "It seems that this week's operation had been in preparation for months, with an acceleration after the operation last year significantly weakened Iranian air defences," Horowitz said. The United States and other Western countries, along with Israel, accuse Iran of seeking a nuclear weapon. Tehran denies that, but has gradually broken away from its commitments under a 2015 nuclear deal it struck with world powers, which the United States withdrew from during President Donald Trump's first term. The landmark accord had provided Iran sanctions relief in exchange for curbs on its atomic programme. 'Impressive' precision Israel is long believed to have carried out sabotage operations inside Iran through its Mossad espionage agency, but the attacks that started on Friday are by far the broadest in scope. The campaign has shown Israel to be capable of precisely locating and taking out high-ranking Iranian officials and nuclear scientists. A European security source said the strikes showed "an impressive degree of precision and mastery". Israel says it has killed 20 military and security targets, including the armed forces' chief of staff and the head of Iran's Revolutionary Guards, as well as nine nuclear scientists. Danny Citrinowicz, of the Tel Aviv-based Institute for National Security Studies, said the ability to take out high-ranking officials showed "intelligence, but also operational superiority of Israel over Iran". "It's highly connected to the ability to collect information, intelligence in Iran for years, excellent intelligence that actually allows you to detect where they're living, the seniors, also the nuclear scientists," he told AFP. The latest targeted strikes come after Israel killed Ismail Haniyeh, the political leader of the Palestinian militant group Hamas, in a Tehran guesthouse in July last year. Haniyeh had been in town for the inauguration of Iranian President Masoud Pezeshkian, and was reportedly killed by an explosive device that Israeli operatives had placed in the guesthouse weeks before. Analysts at the time saw the attack as a major intelligence failure by Iran. But "still Iran didn't learn and didn't have the ability to lock the holes in their system", said Citrinowicz. Smuggled drones News site Axios reported that Mossad agents inside Iran helped prepare Friday's strikes, pre-positioning weapon systems near air defence targets, including by hiding them inside vehicles, and launching them when the attack started. An Israeli intelligence official told Axios that Mossad had "established an attack drone base inside Iran with drones that were smuggled in long before the operation". A former Israeli intelligence official told The Atlantic that "Iranians opposed to the regime make for a ready recruiting pool", and that "Iranians working for Israel were involved in efforts to build a drone base inside the country". Alain Chouet, the former number three in the French intelligence, said he was convinced Israel had "half a dozen cells capable of acting at any moment" inside Iran. Iran regularly executes people it accuses of spying for Israel. It is unclear what role, if any, Israel's key military and diplomatic ally the United States had in the latest strikes. Before the attack early on Friday, Trump publicly urged Israel to allow time for diplomacy, as a sixth round of US-Iranian nuclear talks were set to be held in Oman at the weekend. The US president on Sunday said Washington "had nothing to do" with ally Israel's campaign. But Iran's Foreign Minister Abbas Araghchi on Sunday said Tehran had "solid proof of the support of the American forces and American bases in the region" for the attacks. And Israel's Prime Minister Benjamin Netanyahu said on Saturday his country was acting with "the clear support of the president of the United States".
