Verastem Oncology (NASDAQ:VSTM), a biopharmaceutical company with a market capitalization of $369 million focused on developing treatments for RAS/MAPK pathway-driven cancers, announced the FDA has cleared its Investigational New Drug (IND) application for VS-7375, a KRAS G12D inhibitor, for clinical evaluation. The company plans to initiate a Phase 1/2a study in mid-2025 to test the drug’s safety and efficacy in advanced solid tumors.
The trial will target advanced KRAS G12D mutant solid tumors, including pancreatic, colorectal, and non-small cell lung cancers. Verastem’s partner, GenFleet Therapeutics, is set to present initial results from the Phase 1/2 study of VS-7375 at the ASCO Annual Meeting from May 30-June 3, 2025, in Chicago, with data under embargo until May 22, 2025. The market has responded positively to recent developments, with the stock showing a remarkable 42% return over the past week and 115% over the last six months.
Dan Paterson, Verastem’s president and CEO, expressed optimism about the clinical program for VS-7375 in the U.S., citing promising initial results from GenFleet’s dose escalation work in China. Paterson highlighted the drug’s dual inhibition of KRAS G12D’s ON/OFF states and its potential for deep, durable cancer responses when combined with other agents.
The upcoming U.S. Phase 1/2a study will assess VS-7375’s safety and efficacy, building on GenFleet’s study findings that identified an efficacious starting dose and observed partial responses in patients with pancreatic and advanced lung cancers.
The U.S. Commerce Department said Wednesday it is opening a probe into national security impacts of imports of medium-duty and heavy-duty trucks and related parts into the United States.
The "Section 232" investigation could form the basis of grounds to impose new tariffs on work trucks. The department is seeking public comment by mid-May on the extent to which domestic production of trucks and truck parts can meet domestic demand and the concentration of United States imports of trucks and truck parts from a small number of suppliers.
U.S. President Donald Trump is planning to spare carmakers from some tariffs, The Financial Times reported on Wednesday, citing two people with knowledge of the matter.
Car parts would be exempted from tariffs that are being imposed on imports from China over fentanyl and tariffs levied on steel and aluminum, the report added.
Threats from the Trump administration to impose significant tariffs on European goods, potentially including pharmaceuticals, have cast a shadow of uncertainty over the transatlantic trade relationship. This comes against a backdrop of already booming pharmaceutical exports from European Union (EU) member states to the United States, such as Ireland, whichrecently witnessed a 450% surgefrom €1.9 billion in February 2024 to €10.5 billion in February this year.
These external pressures add fresh urgency to ongoing debates within the EU about how to best regulate its own pharmaceutical sector, balancing industry competitiveness with patient welfare.
“It’s vital that medicines remain as accessible as possible to the UK and global markets. Patients should not end up the casualties in a global trade war,” Alwyn Fortune, the policy lead for the Royal Pharmaceutical Society’s Medicines Shortages Advisory Group, London, England, told Medscape Medical News. “Supply chain vulnerabilities make it harder for patients to access treatment, causing frustration, anxiety, and, in some cases, harm to patient health.”
What EU Pharma Industry Asks
Even before recent trade threats emerged, the European Federation of Pharmaceutical Industries and Associations (EFPIA) advocated for substantial policy reforms to maintain Europe’s position as a hub for innovation, particularly against competition from the United States and China. Their requests fall into four main categories:
Strengthened intellectual property (IP) protection: The industry views robust IP rights as fundamental. “IP is the backbone of our innovation, so without it, we’re not innovating,” Roberta Savli, executive director for Public Affairs at the EFPIA, told Medscape Medical News. In the EU, pharmaceutical reforms introduced in 2023 included shortening the period in which new medicines are protected by data exclusivity. While there are possible extensions for drugs that meet special needs or involve public research, many in the industry worry that these changes could make Europe less attractive for developing innovative medicines, especially for rare diseases. The EU is also considering a patent package to create a unified system for supplementary protection certificates across most EU countries. This would make it easier and cheaper for companies to protect their inventions in Europe. However, the package also includes new rules for compulsory licensing, which would allow governments to override patent protections during emergencies. While this could improve access to medicines in a crisis, Savli said the industry is concerned that it would affect innovation and the rights of patent holders. On the global stage, the World Health Organization released on April 16 a pandemic agreement for consideration at the upcoming World Health Assembly in May that requires countries to share technology and know-how needed to produce vaccines and treatments during health emergencies. Some countries want these transfers to be mandatory if voluntary sharing fails, while pharmaceutical companies and some governments argue that this could undermine incentives for innovation, Savli explained.
An improved regulatory environment: EFPIA is also calling for speeding up the European Medicines Agency (EMA) processes. EMA approvals take roughly 4 months longer than in the United States or Japan. While the ongoing pharmaceutical legislation reform initially proposed faster, flexible pathways (like PRIME, which is currently used more sparingly in the EU than similar pathways in the United States) and shorter assessment times, there are fears that member states might resist these changes, Savli said. Also, achieving true harmonization for clinical trials across the EU remains a challenge due to differing national requirements, complicating vital research and delaying patient access to potentially breakthrough treatments, she explained.
Legislative coherence and simplification: Savli highlighted conflicts between different policy areas. For instance, environmental goals under the Green Deal could lead to bans on substances (like per- and polyfluoroalkyl substances or titanium dioxide) essential for manufacturing medicines, potentially clashing with initiatives like the Critical Medicines Act aimed at boosting European production. “They should talk to each other. These decisions shouldn’t be taken in silo because this is not the way to work well,” Savli said. Proposed revisions to the wastewater treatment directive, which is a directive that is looking at cleaning up micro-pollutants in water, are also seen as unfairly targeting the pharmaceutical sector. “[The EU] is only asking two sectors, the cosmetic and the human pharmaceutical, to pay for the pollution caused by all other sectors.”
An ecosystem that values innovation: Central to industry concerns is how innovation is rewarded, primarily through national pricing and reimbursement systems. EFPIA argues that, compared with the United States, European systems don’t sufficiently value innovation, leading to “rebates and drawbacks” that diminish competitiveness, Savli said. Complex national and even regional processes lead to significant delays in patient access after EMA approval. “On average, Europeans get access to medicines 18 months after the marketing authorization,” she said, with wide disparities between countries. Proposed solutions include better implementation of joint Health Technology Assessments, managed entry agreements, and equity-based tiered pricing.
Roberta Savli
Medscape Medical News reached out to the European Commission spokesperson responsible for health and to the EMA. They both declined an interview.
Patient Care Priority
While the industry focuses on competitiveness and innovation, frontline physicians stress the immediate impact of system pressures on patient well-being. Tiago Villanueva, a family physician in Portugal and the president of the European Union of General Practitioners, highlighted medicine shortages as the primary concern arising from the current uncertainty.
Tiago Villanueva
“Any issue with shortages of medicines may compromise the quality of patient care because you are forced to use medicines that may not be as effective,” Villanueva told Medscape Medical News.
Fortune agreed. “Our report on medicines shortages highlighted that increasing regulatory divergence between the UK and EU is adding to supply chain problems. The ongoing review of EU pharmaceutical regulation will inevitably have implications for the UK.”
Villanueva said shortages and high costs drive a worrying trend: Patients seeking medicines online. This “is not a risk. That’s already happening,” warned Villanueva. Patients turn to “very doubtful places” online, primarily due to the lack of availability of prescribed drugs like Ozempic or to look for newer, expensive weight loss medications not covered by national health systems. The danger is significant. “You cannot be sure that it’s going to be a trustworthy medicine. It could be counterfeit. It could be less effective. It could be actually something else.”
Despite industry calls for faster drug approvals, Villanueva expressed confidence in the existing regulatory safeguards. “We should have full trust in our European medicines regulator,” he said, believing that expedited processes seen during the pandemic streamlined bureaucracy without compromising rigorous safety checks.
While promoting innovation is crucial, he argued, it must be balanced with rigorous testing and ensuring access to safe, reliable medicines through a strong regulatory framework. “Above all, patient care and safety are the most important things.”
Villanueva reported no relevant financial relationships.
The US Food and Drug Administration (FDA) has given Breakthrough Device Designation to Orchestra BioMed for its atrioventricular interval modulation (AVIM) therapy for patients withuncontrolled hypertension.
AVIM is a pacing algorithm incorporated into dual-chamber pacemakers to treat hypertension. It delivers repeating sequences of shorter and longer atrioventricular delays,lowering blood pressure while simultaneously modulating the autonomic nervous system.
The Breakthrough Device Designation is for an implantable system — a pacemaker — to deliver AVIM therapy in patients with increased 10-year atherosclerotic cardiovascular disease risk, preserved left ventricular systolic function, and uncontrolled hypertension, despite the use of anti-hypertensive medications or in patients who may have intolerance to anti-hypertensive medications. Orchestra BioMed estimates that there are more than 7.7 million patients in the US that meet these criteria.
A Pacemaker for Hypertension
"We are delighted to have received FDA Breakthrough Device Designation for AVIM therapy which has the potential to offer a differentiated, advantageous solution for hypertension management in a broad population," said David Hochman, CEO of Orchestra BioMed.
A double-blind, randomized pilot study called MODERATO II showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour ambulatory systolic blood pressure and 12.3 mmHg in office systolic blood pressure after 6 months compared with control patients.
Another pivotal trial run in collaboration with Medtronic, called BACKBEAT, is currently evaluating the safety and efficacy of AVIM therapy in lowering blood pressure in patients who have been indicated for, and recently implanted with, a dual-chamber cardiac pacemaker.
"Hypertension remains a significant global public health challenge that is especially relevant to the pacemaker population as the most common comorbidity in these patients," said Robert C. Kowal, MD, vice president of cardiac pacing therapies within the Medtronic Cardiac Rhythm Management operating unit. "Medtronic is committed to collaborating with Orchestra BioMed to advance this innovative, investigational therapy through the BACKBEAT global pivotal study."
But AVIM therapy is designed to have broad clinical applicability beyond patients with hypertension who require a pacemaker. So, there are also plans to extend this approach to patients with uncontrolled hypertension who would not otherwise have a pacemaker.
"There are millions of patients without a pacemaker indication who have uncontrolled hypertension and are at increased cardiovascular risk who we believe may benefit from a device-based treatment like AVIM therapy," said Avi Fischer, MD, senior vice president of medical affairs and innovation at Orchestra BioMed. "It is our long-term vision that AVIM therapy will be used as a potent, always-on, programmable therapy for hypertension that does not rely only on adherence to daily oral medications – one of the greatest challenges in current standard of care – regardless of whether there is an indication for a pacemaker."
The FDA's Breakthrough Device program is intended to accelerate the development and provide priority review of new medical technologies that have the potential to significantly improve outcomes for patients with serious or life-threatening conditions. It also allows AVIM-enabled devices to qualify for higher reimbursement from the Center for Medicare & Medicaid Services in the future.
