For families facing ultra-rare genetic conditions, traditional drug development timelines often offer little hope. In response, the FDA has proposed a “plausible mechanism” pathway that would allow highly individualized therapies – including gene-editing approaches – to be evaluated based on strong biological rationale and targeted evidence even when large trials are not feasible

Commissioner Marty Makary penned an op-ed in The Wall Street Journal detailing the FDA’s changes, while HHS Secretary Robert F. Kennedy Jr. said the move is intended to “cut unnecessary red tape, align regulation with modern biology, and clear a path for breakthrough treatments.”

But the announcement raises more questions than answers:

1. Which therapies would qualify? Would the pathway be limited to gene therapies and treatments for ultra-rare conditions? Washington University’s Rachel Sachs cautioned that the “plausible mechanism” could be expanded into more ‘common’ disease areas where traditional trials are feasible, and that it wouldn’t be necessary to go through this pathway.”
2. What operational details are still missing? Key elements related to manufacturing and toxicology remain undefined, which former FDA official Janet Woodcock noted could materially affect development costs and feasibility.
3. How high will the evidentiary bar be? Despite FDA’s promise of flexibility, stakeholders question whether it will hold. “Several recent complete response letters indicate a hesitation to apply regulatory flexibility,” Annie Kennedy, chief mission officer of the EveryLife Foundation for Rare Diseases, testified at a Senate hearing yesterday.
4. Is the broader ecosystem equipped to make this pathway work? Clinical trials for ultra-rare conditions remain difficult to conduct. “Add regulatory uncertainty, high per-patient development costs, and uneven access to diagnostic testing and expert clinical care – it is easy to see why promising science stalls,” said Rebecca Ahrens-Nicklas of Children’s Hospital of Philadelphia.
5. Will this restore industry confidence? Recent FDA reversals have strained trust. A spokesperson for the Alliance for Regenerative Medicine said the framework “cannot distract from recent FDA regulatory surprises” affecting rare disease programs.

– Leah Nebbia, Senior Group Director

Most favored nation drug pricing has moved from slogan to stress test. The reactions and submitted comments to two CMS models – GLOBE (covering Medicare Part B) and GUARD (Part D) – reveal just how quickly the international-based pricing policy is colliding with legal, operational and business realities.

• Trade groups for biopharma are sharpening knives, not pencils. PhRMA and BIO argue the GLOBE and GUARD demos aren’t real “tests” at all, but preloaded mechanisms to extract rebates – sometimes in ways they say appear punitive, constitutionally suspect and beyond the regulator’s authority. Drugmakers also warn the approach imports foreign-style valuation frameworks that can narrow access, which would openly lay the groundwork for court fights if the demos are finalized.
• Hospitals see a cost boomerang coming. The American Hospital Association backs the goal of lower prices but warns the models could raise hospitals’ drug acquisition costs if manufacturers reshape pricing and discount channels to reduce rebate exposure. AHA also flags points of operational chaos: identifying who’s “in” the randomized cohort in real time, handling coinsurance when supplemental coverage blunts out-of-pocket changes, and the lack of a clear appeals pathway when CMS miscalculates.
• Small- and mid-size biotechs say licensing could become collateral damage. Companies that out-license ex‑U.S. rights argue they often don’t control foreign pricing –or even have visibility into it – yet could still be held liable under international benchmarks. They warn such demos could turn partnering into a “poison pill,” chilling the licensing deals that fund R&D and help smaller innovators survive.

Across the health care industry, the message is consistent: These Medicare demos may be marketed as affordability tools, but stakeholders fear both could function as a high-stakes test of supply chains, contracting structures and the legal limits of innovation itself.

– Regan Thompson, Senior Manager

President Donald Trump addressed Congress in an annual State of the Union speech that sought to reclaim the political narrative on economic gains and affordability initiatives, including drug pricing.

In remarks lasting a record 107 minutes, Trump spent about three minutes touting how his administration has reduced “wildly inflated” U.S. drug prices. Trump cited his MFN approach as the reason that drug prices are now “the lowest anywhere in the world,” with discounts of “600% and more.”

While he did not debut new health-related policies, the president reiterated calls for Congress to pass legislation mandating MFN drug pricing in the U.S., acknowledging some hesitation among Senators but urging them to “codify it anyway.” PhRMA President and CEO Stephen Ubl released a statement saying that such a policy “would undermine U.S. competitiveness” rather than build on the “historic” PBM reforms signed into law weeks ago.

Guests in attendance on Tuesday night included the first customer of the recently launched TrumpRx who – as called out by the president – purchased discounted fertility medication through the site. Several Democratic members of Congress also invited constituents who they say now face “skyrocketing” insurance premiums as a result of federal inaction.

– Andrew Wishon, Senior Manager

• March 2-3 – a ‘BIG’ Investment & Growth Summit, BIO

• “Policies have declared and undeclared purposes. We analyze the pros and cons of policies like Trump Rx or MFN…The political strategy behind them is usually undeclared but almost everything in health policy between now and November will be substantially about the midterms.” – Drew Altman, KFF
• “The president needs an FDA that abides by its commitments and implements his vision for the future of medicine. We can help thousands of rare disease patients right now – and millions more in the future – with an FDA that follows his call.” – Tim Hunt, New York Post
• “Today, pharmacy benefit managers and other middlemen often profit when prices stay high. Negotiated discounts can disappear before they ever reach the patient. That’s not reform, that’s a shell game.” – Sen. Ruben Gallego, D-Ariz., The Hill

• NPR shared the story of a patient with retinitis pigmentosa, a rare genetic eye condition, to illustrate how gene therapies are inaccessible for many due to a lack of insurance coverage. NPR: Gene therapy is transforming lives, but for many Americans it’s hard to reach.
• EU officials paused work on a trade deal with the U.S. that would cap tariffs on European exports at 15% after the U.S. Supreme Court ruled that President Trump’s unilateral imposition of tariffs constituted presidential overreach. Fierce Pharma: Europe pumps brakes on US trade deal after Supreme Court decision, Trump tirade.
• President Trump’s nominee for surgeon general, Casey Means, still lacks sufficient votes for confirmation following a testy Senate hearing on Wednesday. POLITICO: Trump’s surgeon general pick, Casey Means, still lacks votes for confirmation.
• Despite Novo Nordisk slashing the list prices of its GLP-1 drugs, the net prices are expected to see little change, thus limiting the number of payers willing to provide coverage. STAT: Will Novo Nordisk’s slashing of obesity drug prices save patients’ money? It depends.
• The CDC’s vaccine advisory committee rescheduled its winter meeting to March 18-19 and shared plans to discuss, among other topics, COVID-19 vaccine safety. Fierce Pharma: After delay, CDC vaccine panel sets new dates to discuss long COVID and mRNA shot safety.
• Only about 10% of the $600 billion in U.S. biopharma investments declared in 2025 has appropriated amounts and planned locations. Pharma Manufacturing: Big Pharma’s $600B US investment plans are short on details: CBRE.
• As part of a new pilot program, the FDA will reportedly offer bonuses to employees who complete drug reviews ahead of schedule. Associated Press: FDA to offer bonus payments to staffers who complete speedy drug reviews.
• Fifteen Democrat-led states sued HHS over changes to the vaccine schedule that reduced the number of diseases children are routinely immunized against from 17 to 11. The New York Times: 15 States Sue H.H.S. Over Revisions to Vaccine Schedule.
• Cigna acquired CarepathRx, a pharmacy that supplies prescription drugs to 10% of U.S. hospitals, further expanding the insurer’s reach within the health care industry. STAT: Cigna, extending reach into prescription drugs, acquires major pharmacy used by hospitals.