Navigating Drug Approvals

🚨 Huge News in Bladder Cancer: The FDA has approved INLEXZO™ (gemcitabine intravesical system) from Johnson & Johnson - the first and only drug-releasing system for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with CIS. Bladder cancer is the 10th most common cancer worldwide, with ~600,000 new cases annually. Many of whom have had limited treatment options for decades, often requiring bladder removal surgery. Not anymore. Clinical Highlights: - 82% complete response in Phase 2b SunRISe-1 trial - 51% remained cancer-free ≥1 year - Inserted in minutes in an outpatient setting, up to 14 cycles INLEXZO™ represents: ✔ First sustained drug-releasing system for bladder cancer ✔ Bladder-sparing alternative for patients unresponsive to BCG ✔ Durable efficacy with a manageable safety profile 👏 Congratulations to the bladder cancer community and J&J on this historic milestone in oncology. #oncology #biotech #pharma #CGTweekly #cancer

FDA just changed the rules of the oncology game: survival is the scoreboard. For years, companies leaned on surrogate endpoints—progression-free survival, tumor shrinkage, biomarkers. Flashy. Fast. But not always life. Now the FDA’s draft guidance makes it clear: → Overall survival (OS) should be the primary endpoint in randomized cancer trials when feasible → Even when it’s not, sponsors must collect and prespecify OS data—because safety and efficacy live there → Design fixes are coming for crossover, unequal randomization, and long-term follow-up Why it matters: as FDA and AACR leaders put it, we’ve seen cases where progression-free survival looked great—but patients didn’t live longer. Sometimes, they lived shorter. That’s unacceptable. This is a reset. Biotechs, CROs, CDMOs: if your trials don’t put survival front and center, you’re not future-proof—you’re playing the wrong game. The only metric patients care about is time. Is your company ready to measure up?

The FDA has issued a warning letter to Catalent Indiana, now under Novo Nordisk, citing serious CGMP failures in sterile manufacturing. The details matter; repeated extrinsic contamination, weak investigations, aborted media fills treated as routine but the lesson is broader. Quality does not reset with an acquisition. And it doesn’t improve just because a stronger owner shows up. In sterile manufacturing, quality is a leadership discipline. When contamination signals are managed as operational inconveniences instead of existential risks, regulators will eventually step in, regardless of who owns the asset. I’ve written this many times before, and this case reinforces it: Most quality crises are not caused by bad equipment or suppliers. They’re caused by governance gaps. Logos change. Accountability doesn’t. 🔔 Follow for more insights ♻️ Share if useful #catalent #novonordisk #gmp #quality #cdmo #cmo

The FDA’s latest complete response letter to Genentech signals a significant shift in how global oncology trials will be evaluated in Washington. Columvi + GemOx failed to secure a U.S. label for second‑line DLBCL. The FDA stated that the STARGLO study did not demonstrate a benefit for American patients and returned the application for additional U.S. data. Last September, the FDA published draft guidance stating that sponsors of multiregional oncology trials must include a “robust” U.S. cohort or prespecified bridging analyses. New Commissioner Marty Makary M.D., M.P.H., has since reiterated this stance, emphasizing diversity and domestic relevance in every advisory meeting. The U.S. data from STARGLO was weak: 🔹  Only 9% of the 364 patients were treated in the United States. 🔹 In a subgroup analysis, the Columvi combo increased the risk of death by 6 percent in non‑Asian regions, even though the global read‑out looked positive. Analysts had pencilled in up to $2 billion in peak sales for the drug. A typical launch would have delivered $150‑200 million in year one. That's now pushed to 2026-2027 while the team gathers more U.S. data. The takeaway? If a pivotal study looks world‑class everywhere except the United States, assume it is no longer approvable. Bake a ~20 percent U.S. accrual target, or a rigorous bridging plan, into every protocol from day one. That adjustment may raise budgets in the short term, but it is cheaper than a missed launch and a surprise CRL. Article: https://lnkd.in/e-GEBUYe

🚨 𝗕𝗿𝗲𝗮𝗸𝗶𝗻𝗴 𝗻𝗲𝘄𝘀 𝗳𝗿𝗼𝗺 𝗙𝗗𝗔 Drug approval no longer starts with a trial. It starts with a mechanism. The FDA has introduced the “𝗽𝗹𝗮𝘂𝘀𝗶𝗯𝗹𝗲 𝗺𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝗺” 𝗽𝗮𝘁𝗵𝘄𝗮𝘆: a new route to approve bespoke therapies when classic trials are impossible.  Think N-of-1 gene editing for ultra-rare, often fatal childhood diseases. 𝟱 𝗲𝗹𝗲𝗺𝗲𝗻𝘁𝘀 𝘁𝗵𝗲 𝗙𝗗𝗔 𝘄𝗮𝗻𝘁𝘀 𝘁𝗼 𝘀𝗲𝗲 𝗯𝗲𝗳𝗼𝗿𝗲 𝗮𝗽𝗽𝗿𝗼𝘃𝗮𝗹 1️⃣ 𝗖𝗹𝗲𝗮𝗿 𝗺𝗼𝗹𝗲𝗰𝘂𝗹𝗮𝗿 𝗰𝗮𝘂𝘀𝗲 A single, well-defined genetic or molecular defect driving the disease. 2️⃣ 𝗧𝗵𝗲𝗿𝗮𝗽𝘆 𝗱𝗲𝘀𝗶𝗴𝗻𝗲𝗱 𝘁𝗼 𝗳𝗶𝘅 𝘁𝗵𝗮𝘁 𝗱𝗲𝗳𝗲𝗰𝘁 The product must target the precise mechanism: the edit, splice, or RNA change that corrects the biology. 3️⃣ 𝗪𝗲𝗹𝗹-𝘂𝗻𝗱𝗲𝗿𝘀𝘁𝗼𝗼𝗱 𝗻𝗮𝘁𝘂𝗿𝗮𝗹 𝗵𝗶𝘀𝘁𝗼𝗿𝘆 Strong historical data showing how the disease progresses without treatment, so real benefit is clear. 4️⃣ 𝗘𝘃𝗶𝗱𝗲𝗻𝗰𝗲 𝗼𝗳 𝘁𝗮𝗿𝗴𝗲𝘁 𝗲𝗻𝗴𝗮𝗴𝗲𝗺𝗲𝗻𝘁 Proof the therapy does what it’s meant to do, through biomarkers, biopsies, or validated non-animal models. 5️⃣ 𝗠𝗲𝗮𝗻𝗶𝗻𝗴𝗳𝘂𝗹 𝗰𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝗯𝗲𝗻𝗲𝗳𝗶𝘁 Improvements strong enough that they cannot be dismissed as noise. A single patient can serve as their own control. If a platform shows success in several different patients, even with unique bespoke edits, the FDA can move toward platform-level authorization, not just case-by-case exemptions. 👉 𝗪𝗵𝘆 𝘁𝗵𝗶𝘀 𝗺𝗮𝘁𝘁𝗲𝗿𝘀 𝗳𝗼𝗿 𝗽𝗮𝘁𝗶𝗲𝗻𝘁𝘀  For families facing ultra-rare genetic diseases, the old logic was brutal: too rare for trials → no drug → no options. This pathway changes that:  • From “too rare to study” → “biologically defined and actionable.”  • From isolated compassionate-use miracles → a structured regulatory route.  • From decade-long timelines → months from design to first dosing in the most urgent pediatric cases. And it does not end at approval:  • Long-term real-world evidence  • Ongoing monitoring for off-target edits, immune issues, developmental risks  • Registries to track durability and outcomes 👉 𝗪𝗵𝗼 𝗯𝗲𝗻𝗲𝗳𝗶𝘁𝘀 𝗳𝗶𝗿𝘀𝘁?  • Infants with lethal monogenic diseases  • Ultra-rare disorders with a single known driver mutation  • Small, genetically defined subsets in oncology and immunology 𝗜𝘁’𝘀 𝗮 𝗯𝗶𝗼𝗹𝗼𝗴𝘆-𝗳𝗶𝗿𝘀𝘁, 𝗽𝗹𝗮𝘁𝗳𝗼𝗿𝗺-𝗯𝗮𝘀𝗲𝗱 𝗮𝗽𝗽𝗿𝗼𝗮𝗰𝗵 𝗯𝘂𝗶𝗹𝘁 𝗳𝗼𝗿 𝗰𝗼𝗻𝗱𝗶𝘁𝗶𝗼𝗻𝘀 𝘄𝗵𝗲𝗿𝗲 𝗹𝗮𝗿𝗴𝗲 𝘁𝗿𝗶𝗮𝗹𝘀 𝘄𝗶𝗹𝗹 𝗻𝗲𝘃𝗲𝗿 𝗯𝗲 𝗽𝗼𝘀𝘀𝗶𝗯𝗹𝗲. It’s a design guide for how to build your next platform and IND package. Because for many families, this is the first time “𝘆𝗼𝘂𝗿 𝗯𝗶𝗼𝗹𝗼𝗴𝘆 𝗶𝘀 𝘂𝗻𝗶𝗾𝘂𝗲” doesn’t automatically mean “𝘆𝗼𝘂’𝗿𝗲 𝗼𝗻 𝘆𝗼𝘂𝗿 𝗼𝘄𝗻.”

While Europe gets stuck, Switzerland and the UK move forward. Switzerland has already taken the leap: it will soon allow medical devices approved by the US FDA onto its market. And now the United Kingdom is following suit: the MHRA is creating new “reliance routes” to fast-track devices already cleared by trusted regulators (FDA, Health Canada, TGA…). Two countries outside the EU… yet clearly closer to innovation than the Continent itself. Meanwhile, the EU MDR has become a regulatory maze, suffocating established players and start-ups alike, and delaying patient access to life-saving technologies. The result? European innovations are now being approved in the US first … and only years later, if ever, find their way back to Europe. It’s time to wake up. Europe cannot remain trapped in a system designed to ensure safety but that now stifles progress. We must reform the MDR or finally recognize approvals from trusted agencies. Because every year we lose to bureaucracy, we lose a piece of European medical innovation. #MedTech #Innovation #Regulation #MDR #FDA #MHRA #Swissmedic #Europe #HealthTech #MedicalDevices

In 1960, a new FDA medical reviewer took a stand. Her story is more important than ever. Frances Oldham Kelsey refused to approve thalidomide. She wasn't convinced it was safe. (This was a drug widely used in Europe.) Pushing back against pharmaceutical companies was rare. But Kelsey demanded more data. She kept asking for: - Long-term safety studies  - Proof of no harmful side effects  - Comprehensive clinical trial results The company delayed, dismissed, and resisted. But she stood firm. Meanwhile, doctors overseas kept prescribing the drug. Soon, babies were born with severe birth defects.  Not dozens. 𝘛𝘩𝘰𝘶𝘴𝘢𝘯𝘥𝘴. Kelsey’s persistence prevented further tragedy. Her work led to: - Stricter drug approval laws  - Mandatory proof of effectiveness  - Better safeguards for public health Regulations exist for a reason. The public can’t vet every device and drug themselves. FDA's role in safety is undeniable. (Whatever your view of them may be.)

I spent 9 years at FDA. The thing that shocks founders most? Your reviewer is learning about your technology for the first time. From your submission. That's not a flaw in the system. That IS the system. FDA reviewers are lay scientists, engineers, and clinicians. Smart people. But stretched across thousands of device types. That neurologist reviewing your cardiovascular device? That software engineer evaluating your surgical tool? They're generalists doing their best with limited time. I've watched brilliant founders assume FDA "gets it." They submit dense technical documentation written for peers. They use industry shorthand. They skip fundamentals because "obviously FDA knows this." No. They don't. FDA covers everything from tongue depressors to brain implants. No one can be an expert in all of it. This blind spot kills more first submissions than anything else I see. The fix feels almost too simple: Write like you're explaining your device to an intelligent non-specialist. → Define every term → Include diagrams a curious teenager could follow → Explain the basic science even when it seems obvious → Use analogies that translate across fields → Show exactly how your device fits the regulatory landscape A client recently came to me convinced they needed a De Novo. "Nothing like this exists," they said. I found three solid predicates in under fifteen minutes. The technology wasn't the problem — the translation was. Your reviewer wants to clear your device. But first they need to understand what it actually does. Stop writing for the expert you wish was assigned. Write for the smart generalist you'll actually get. What's the most surprising knowledge gap you've run into with a reviewer? #FDASubmission #MedicalDevices #RegulatoryAffairs #MedTech

🔥 7 Challenges Slowing the ADC Revolution 🔥 💡 The ADC Boom: ADCs are the hottest ticket in oncology, blending antibody precision with chemotherapy’s punch. With 11 FDA approvals, 378 clinical candidates, and a market set to hit $30B by 2030, these therapies promise to redefine cancer care. ⚠️ BUT… Hidden Challenges Lurk: While stars like Enhertu (T-DXd) and Trodelvy (SG) grab headlines, 150+ ADCs have failed, and even approved drugs face toxicities, resistance, and delivery flaws. The gap between hype and reality is widening. 👇 Here’s the unfiltered breakdown of 7 make-or-break challenges the industry MUST solve: 1️⃣ TOXICITY TRAP 🚑 A) >90% of ADC patients face adverse events (46% severe). B) Payloads like auristatins (neuropathy) and maytansinoids (liver toxicity) drive “platform toxicities.” Example: ARX788 (HER2 ADC) halted trials due to 46% keratitis rates. 2️⃣ LINKER INSTABILITY ⚖️ A) 50% of maleimide-based ADCs (e.g., T-DXd) shed payloads in blood, binding to albumin. B) SG’s carbonate linker releases SN38 in <24h, raising toxicity risks. 3️⃣ TUMOR UPTAKE FAILURE 🎯 A) <1% of ADC doses reach tumors. PET scans show most ADCs pool in liver/spleen. B) Shocker: Only 0.9% ID of ⁸⁹Zr-trastuzumab accumulates in HER2+ tumors. 4️⃣ BIOMARKER BLIND SPOTS 🔍 A) HER2 PET imaging reveals 26% of “HER2+” patients are PET-negative, with 3x shorter survival on T-DM1. B) TROP2 ADCs like SG show no OS benefit in Phase III lung cancer (EVOKE-01). 5️⃣ CROSS-RESISTANCE RISKS 🔄 a) Real-world data: Sequencing TOPO1i ADCs (SG → Dato-DXd) cuts PFS from 7.3 → 4.4 months. B) China study: 2nd-line same-payload ADCs drop ORR to 5.3% vs. 22.6% for new mechanisms. 6️⃣ CLINICAL FAILURE CURSE 🚫 A) 150+ ADCs discontinued (e.g., DP303c: 95% keratitis). B) Site-specific tech (DCDS0780A) failed vs. polatuzumab vedotin due to ocular toxicity. 7️⃣ COMBO COMPLEXITY 💣 A) Enfortumab + pembrolizumab doubled OS in bladder cancer… but 46% Grade 3+ toxicities. Food for thought - ADCs are not a guaranteed win. Prioritize companies tackling: 1) Payload innovation (STING agonists, protein degraders). 2)Biomarker-driven trials (HER2 PET, ctDNA). 3)Tumor-selective delivery (pH-sensitive antibodies, peptide masks). Drop a comment: Which ADC player are you betting on? #ADCs #Biotech #Oncology #DrugDevelopment #Investing #Healthcare #investor #startup #pharma

8 Tips for better Post-Market Surveillance (PMS)↴ Want to improve your PMS process? 1/ Build a feedback loop Regularly update & align: Clinical evaluation / Risk management / PMS process The data available of your device evolves, so ALWAYS adapt your strategy! 2/ Link your PMS with Risk Management Link your PMS to risk mngmt. process; note that risk management must drive your overall strategy Close gaps by addressing uncertainties with targeted data collection. 3/ Use multiple data sources Go beyond one database; Even if you only sell in Europe, take a look at the US databases - they're a goldmine of information!  Look at: Adverse events / Similar device recalls/ FSNs/FSCAs 4/ Survey the right way Forget satisfaction scores. Ask about: Safety and performance / Effectiveness /Near-miss incidents This will help you meet the PMS objectives outlined in the MDR. 5/ Don't underestimate "usage" data Identify use errors. (Nope, human errors is not a valid root cause) Find the REAL root cause. Update the design if necessary. 6/ Track regional trends Monitor device sales by region. Spot trends early and adjust vigilance reports. (If you sell internationally, adapt your vigilance procedure) 7/ Be indirect about Off-Label use Don’t ask directly (you'll probably never get a real off-labe this way)↴ Ask about all use cases instead. Don't just look for what's wrong, take it all in, and analyse the cases yourself. 8/ Keep accompanying documentation(s) update Update IFUs for new risks. It’s a simple step with big safety impacts. Need more ? Grab our PMS templates (plan + PSUR), take advantage of : → Pre-written paragraphs and tables → Collection and analysis methods → Clear links to MDR 2017/745 and ISO 20416 → Concrete examples with a medical device Save time and be efficient in your PMS → https://lnkd.in/ezMXxxMc