The FDA’s real-time clinical trial announcement is the most structurally significant regulatory initiative since the Expedited IND proposal in March. For 60 years, clinical trial data has followed the same path: collected at sites, sent to sponsors, analyzed, then submitted to the FDA in batches. Under the new Real-Time Clinical Trial framework, the FDA receives aggregated safety and efficacy signals in the cloud as they occur. AstraZeneca’s Phase 2 TRAVERSE trial in mantle cell lymphoma is already transmitting data through Paradigm Health’s platform. Amgen’s Phase 1b STREAM-SCLC trial in small cell lung cancer is in final site selection. Commissioner Makary said nearly half of the typical 10-to-12-year development timeline passes “with no trial actually running.” This initiative aims to compress that dead time. Meanwhile, Novartis reported what the patent cliff actually looks like in real quarterly numbers: Entresto dropped 42% to $1.31 billion after U.S. patent expiration and generic entry, dragging total sales below expectations. The company expects $4 billion in sales erosion this year. And Lilly, apparently unstoppable, signed its sixth deal of 2026—a $2.25 billion AI gene editing collaboration with Profluent Bio that the company’s CEO called an attempt to unlock the “holy grail” of genetic medicine. Lilly reports earnings tomorrow.
Top Story: The FDA Launches Real-Time Clinical Trial Data Monitoring
What Happened: The FDA announced on April 28 two major steps toward implementing real-time clinical trials. First, two proof-of-concept trials are already operational. Second, the agency released a Request for Information on a broader pilot program that will launch this summer. Public comment is open through May 29.
The Two Pilots Already Running
AstraZeneca TRAVERSE (Phase 2): Testing acalabrutinib combination therapy in treatment-naive mantle cell lymphoma. Sites include MD Anderson Cancer Center and University of Pennsylvania. The FDA has already received and validated safety data signals through Paradigm Health’s platform, establishing the technical feasibility of real-time signal sharing.
Amgen STREAM-SCLC (Phase 1b): Testing an undisclosed treatment in limited-stage small cell lung carcinoma. Final site selection is in process.
How It Works: What the FDA Sees (and What It Does Not)
FDA Chief AI Officer Jeremy Walsh said the agency is not seeking access to raw patient records. Instead, sponsors transmit only aggregated signals—adverse event rates, response percentages, endpoint data—via a cloud-based platform operated by Paradigm Health. Individual patient records remain with the trial sponsor. No raw patient data. No identifying information.
This design is critical. It avoids the patient privacy concerns that would have made real-time monitoring politically and legally untenable while still giving the FDA visibility into trial progress as it happens. The FDA sees rates and trends. It does not see patient names, medical records, or site-level identifiers.
Why This Matters for Drug Development Timelines
Commissioner Makary said: “We’re announcing a bold new approach that could fundamentally transform this clinical trial landscape.” He noted that the typical 10-to-12-year drug development timeline includes nearly half the time where no trial is actually running—the dead time between phases, during data analysis, during regulatory submissions, and during FDA review.
Real-time monitoring attacks that dead time from multiple angles. If the FDA can see safety signals in real time, it can potentially shorten the interval between trial phases. Go/no-go decisions that currently require formal data submissions and months of FDA review could be compressed. Safety signals that would otherwise take months to surface in periodic reports could be identified and acted upon in days or weeks.
AstraZeneca oncology SVP Amy McKee called it a step toward moving “data as quickly as possible across this ecosystem.” For sponsors, the value proposition is straightforward: faster regulatory feedback loops mean shorter development timelines and lower costs. For the FDA, the value is earlier visibility into safety and efficacy trends that inform regulatory decision-making.
The Broader Implications
The Request for Information solicits public comment on expanding RTCT to a formal pilot this summer. The RFI does not limit the framework to pharmaceutical trials. Device trials, digital therapeutics studies, and surgical outcomes registries could all eventually adopt real-time signal sharing. For medtech companies running large-scale trials, this could accelerate regulatory submissions. For CROs, real-time data transmission will require new infrastructure and capabilities—companies that integrate real-time signal reporting into their offerings will have a competitive advantage over those that do not adapt.
The limiting factor is standardization. Real-time signal sharing requires agreed-upon data formats, aggregation methods, and signal definitions across sponsors, sites, and platforms. The RFI is the FDA’s way of soliciting industry input on those standards before formalizing the program.
Our Pro brief analyzes how RTCT works at the infrastructure level, which types of trials benefit most, and why this could reshape the CRO industry as fundamentally as electronic data capture did in the 2000s. [Details below.]
What to Watch
The public comment period closes May 29. The pilot program launches this summer. Watch which companies beyond AstraZeneca and Amgen sign on. The pace of adoption will signal how seriously the industry views RTCT as a competitive advantage versus a regulatory burden. The Paradigm Health platform is currently the only FDA-validated infrastructure for RTCT—watch for competing platforms to emerge.
Novartis Misses Q1 as Entresto Falls 42%
What Happened: Novartis reported Q1 2026 results on April 28 that missed expectations across the board. Total net sales were $13.11 billion versus analyst expectations of $13.40 billion (down 5% on a constant-currency basis, down 1% in USD). Core operating income was $4.9 billion, down 12%, below expectations of $5.1 billion. Net income was $3.2 billion, down 13%. Shares fell 3% in premarket trading.
The Entresto Cliff in Real Numbers
Entresto sales dropped 42% to $1.31 billion after U.S. patents expired and generic competitors launched. Analysts had expected $1.37 billion. Entresto was 14% of total net sales last year. European patent expiration begins in November, creating a second wave of generic erosion. Novartis expects $4 billion in total sales decline this year from generics across Entresto and two other drugs.
CEO Vas Narasimhan called this the company’s “largest patent expiry in the last two decades.” The Entresto decline is not a surprise—it was projected and priced into expectations. What caught the market off guard was the magnitude in a single quarter: a 42% drop is steeper than the consensus erosion curve.
The Growth Brands Are Growing—But Not Fast Enough Yet
Novartis’s priority brands delivered strong growth that partially offset the Entresto hole:
Kisqali (breast cancer): +55% constant currency. Pluvicto (prostate cancer): +70% constant currency. Kesimpta (multiple sclerosis): +26% constant currency. Scemblix (leukemia): +79% constant currency. Leqvio (cholesterol): +69% constant currency.
Volume from these growth brands contributed 13 percentage points of growth. But generic erosion subtracted 14 points, resulting in a net decline. The math is simple but unforgiving: the growth brands need to grow faster than the legacy brands are declining. In Q1, they did not quite get there.
The company reaffirmed full-year guidance: low single-digit net sales growth and low single-digit core operating income decline. Management insists growth returns in the second half as the priority brands continue to accelerate and the initial shock of Entresto generic entry moderates. Whether that narrative holds depends on Kisqali and Pluvicto maintaining their 55-70% growth rates through H2 with increasing competition.
The Pattern for the Industry
Novartis is the preview for every major pharma company navigating a patent cliff. The playbook is consistent across the industry: build new brands fast enough to outrun the decline. The Novartis Q1 results show what the transition looks like in real financial data—strong growth brand performance that is temporarily insufficient to offset the mathematical reality of a blockbuster losing 42% of its revenue in a single quarter.
Our Pro brief includes a detailed breakdown of Novartis’s patent cliff math, how the growth brands need to perform in H2 to hit full-year guidance, and what the Entresto erosion curve means for European patent expiration in November. [Details below.]
Lilly Signs $2.25B AI Gene Editing Deal with Profluent Bio
What Happened: Lilly announced a multi-program research collaboration with Profluent Bio on April 28 to develop AI-designed recombinases for genetic medicines. Profluent will receive an undisclosed upfront payment and committed R&D funding, with eligibility for up to $2.25 billion in development and commercial milestone payments plus tiered royalties on net sales. Lilly gets exclusive rights to advance selected recombinases through preclinical, clinical, and commercial development.
The Technology: Beyond CRISPR
Profluent uses AI foundation models to design site-specific recombinases—enzymes that cut and rejoin DNA at precise locations. Unlike CRISPR, which typically makes small edits (single-nucleotide changes or small insertions/deletions), recombinases can insert entire genes at the kilobase scale. Profluent CEO Ali Madani called this “a holy grail in genetic medicine” and said “only AI can create the designer recombinases needed to precisely target any location in the genome.”
The distinction between CRISPR and recombinase-based gene editing matters for therapeutic applications. Many genetic diseases are caused by mutations that require replacing or inserting entire genes—not just correcting a single nucleotide. Recombinases that can precisely insert kilobase-length DNA sequences would enable therapies for conditions that CRISPR, in its current form, cannot efficiently address. Profluent is backed by Jeff Bezos. This is Lilly’s second recombinase-focused deal this year.
Lilly’s 2026 Deal Count Reaches Six
STAT called the collaboration a push “beyond CRISPR.” BioSpace framed it as Lilly “continuing its dealmaking spree as well as its commitment to artificial intelligence.” Lilly’s 2026 deal total now includes six announcements:
Orna Therapeutics: $2.4 billion (in vivo CAR-T, autoimmune). Centessa Pharmaceuticals: $7.8 billion (narcolepsy/OX2R). Kelonia Therapeutics: Up to $7 billion (in vivo CAR-T, myeloma). CrossBridge Bio: Up to $300 million (dual-payload ADC). Ajax Therapeutics: Up to $2.3 billion (Type II JAK2, myelofibrosis). Profluent Bio: Up to $2.25 billion in milestones (AI-designed recombinases).
The Profluent collaboration is structured differently from the first five—a research collaboration with milestones rather than an outright acquisition—but it signals the same strategic direction. Lilly is building the broadest next-generation therapeutics platform in pharma, spanning in vivo CAR-T, ADCs, targeted oncology, neuroscience, and now AI-designed gene editing.
Strategic Themes
1. Real-Time Trial Monitoring Could Compress Drug Development Timelines More Than Any Single Regulatory Reform
The Expedited IND proposal lowers the barrier to entering Phase 1. The CNPV program compresses FDA review to weeks. Real-time trial monitoring attacks the dead time between trial phases—the months spent analyzing data, preparing submissions, and waiting for FDA feedback before advancing to the next phase. Together, these three initiatives represent a systematic effort by Commissioner Makary to reduce the 10-to-12-year development timeline from multiple angles simultaneously. If all three are implemented and adopted broadly, the cumulative effect on development speed could be greater than any single reform.
2. The Entresto Cliff Shows What Patent Expiration Actually Looks Like in a Quarterly Income Statement
42% revenue decline. 12% operating income drop. Missed estimates. Share price down 3%. This is the financial reality of losing patent protection on a drug that represents 14% of total revenue. The growth brands are performing well—Kisqali, Pluvicto, Kesimpta, Scemblix, and Leqvio collectively delivered strong double-digit growth. But in the quarter where the cliff hits hardest, even 55-79% growth rates on emerging brands are mathematically insufficient to offset a 42% decline on a $2+ billion product. Every pharma CFO watching Novartis is running the same numbers on their own patent-exposed franchises.
3. Lilly’s Platform Is Now the Broadest in Pharma—and Getting Broader
Six deals in three months. In vivo CAR-T (two platforms). Narcolepsy. ADCs. Targeted blood cancer therapy. And now AI-designed gene editing. No other pharmaceutical company is building across this many modalities and therapeutic areas simultaneously. The GLP-1 cash generation engine makes the financial deployment possible. Whether the organizational bandwidth supports this breadth of activity—while simultaneously launching Foundayo, filing for a diabetes indication, and managing the existing Zepbound/Mounjaro franchise—is the open question that tomorrow’s earnings call will begin to address.
4. Tomorrow’s Lilly Earnings Are the Most Anticipated Report of the Year
The April 30 call brings together every major Lilly narrative: Foundayo launch trajectory through mid-April, ACHIEVE-4 interpretation and the diabetes filing timeline, six-deal integration strategy and whether a seventh is coming, Zepbound/Mounjaro revenue growth, Section 232 tariff positioning, and the Profluent AI gene editing rationale. The market’s reaction will set the tone for the entire pharma sector heading into ASCO.
Frequently Asked Questions
What is the FDA’s Real-Time Clinical Trial initiative?
A new framework in which the FDA receives aggregated safety and efficacy signals from clinical trials in the cloud as they occur, rather than waiting for periodic data submissions. Two trials are already operational: AstraZeneca’s TRAVERSE trial in mantle cell lymphoma and Amgen’s STREAM-SCLC trial in small cell lung cancer. A broader pilot program launches this summer. Public comment is open through May 29.
Does the FDA see individual patient data?
No. Sponsors transmit only aggregated signals—adverse event rates, response percentages, and endpoint data—through a cloud-based platform. Individual patient records remain with the sponsor. No raw patient data or identifying information is shared.
How does real-time monitoring speed up drug development?
By giving the FDA visibility into trial progress as it happens, which can shorten the interval between trial phases, enable faster go/no-go decisions, and identify safety signals earlier. Commissioner Makary noted that nearly half of the 10-to-12-year development timeline passes with no trial actually running—the dead time between phases, during analysis, and during review.
What happened with Novartis Q1?
Total net sales of $13.11 billion missed the $13.40 billion expectation. Entresto dropped 42% to $1.31 billion after U.S. patent expiration and generic entry. Core operating income fell 12% to $4.9 billion. The company expects $4 billion in total sales erosion this year from generics. Priority brands (Kisqali +55%, Pluvicto +70%, Scemblix +79%) grew strongly but could not fully offset the Entresto decline.
What is the Profluent Bio deal?
A multi-program research collaboration in which Profluent will design AI-engineered recombinases for kilobase-scale gene editing. Profluent receives an undisclosed upfront payment with eligibility for up to $2.25 billion in milestones plus royalties. Unlike CRISPR (small edits), recombinases can insert entire genes. Profluent CEO called it “a holy grail in genetic medicine.” This is Lilly’s sixth deal of 2026 and its second recombinase-focused pact this year.
How many deals has Lilly done in 2026?
Six: Orna ($2.4B), Centessa ($7.8B), Kelonia (up to $7B), CrossBridge (up to $300M), Ajax (up to $2.3B), and Profluent (up to $2.25B in milestones). The deals span in vivo CAR-T, narcolepsy, ADCs, blood cancer, and AI gene editing. Total committed capital across the five acquisitions alone approaches $20 billion.
When is Novartis’s European Entresto patent expiration?
November 2026. This will create a second wave of generic erosion beyond the U.S. decline already underway. Novartis management expects the company to return to growth in H2 as priority brands continue to accelerate, but European generic entry adds another headwind.
What should investors watch at Lilly earnings tomorrow?
Foundayo TRx trajectory through mid-April, ACHIEVE-4 diabetes filing timeline, six-deal integration strategy, Zepbound/Mounjaro revenue, and Section 232 tariff positioning. This is the most anticipated pharma earnings call of the quarter.
BioMed Nexus Pro — What Institutional Subscribers Are Reading Today
RTCT Deep Dive: The Infrastructure Shift. We analyze how real-time clinical trial monitoring works at the platform level, which trial designs benefit most from continuous FDA visibility, and why this could reshape the CRO industry as fundamentally as electronic data capture did two decades ago. If you run clinical trials, this is the framework that will define your next operational upgrade.
Patent Cliff Anatomy: The Novartis Case Study. We break down the Entresto erosion curve quarter by quarter, model how the five priority brands need to perform in H2 to hit full-year guidance, and assess whether European patent expiration in November creates a second earnings miss risk. Every pharma company navigating a patent cliff should study this data.
Lilly Earnings Preview: The Five Numbers That Define Tomorrow. We lay out the data points that will set the tone for the entire pharma sector—Foundayo launch trajectory, ACHIEVE-4 filing status, M&A integration commentary, Zepbound/Mounjaro growth, and tariff margin impact.
Plus: RTCT pilot program adoption tracking, Profluent AI gene editing technology comparison versus CRISPR, Novartis H2 recovery modeling, and the updated catalyst calendar through ASCO and H2 2026.
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