The FDA: Faster, but not nec­es­sar­i­ly bet­ter. And that could threat­en the agen­cy's brand

Faster FDA drug ap­provals may re­flect less rig­or­ous ev­i­den­tiary stan­dards, a new analy­sis sug­gests.

Jonathan Dar­row BWH

In 1962, the reg­u­la­to­ry scruti­ny of med­i­cines by the FDA in­ten­si­fied in re­ac­tion to thalido­mide, an an­ti-nau­sea drug that gained no­to­ri­ety af­ter its link to se­vere skele­tal birth de­fects. Since then, a flood of in­cen­tives has made the US sys­tem of get­ting drugs ap­proved eas­i­er and the agency seem­ing­ly more flex­i­ble. Reg­u­la­to­ry in­cen­tives — such as fast-track and break­through ther­a­py sta­tus, or­phan drug des­ig­na­tions as well as ac­cel­er­at­ed and con­di­tion­al ap­provals — have di­min­ished re­view times and en­cour­aged the use of sur­ro­gate end­points. And while the in­dus­try has en­cour­aged it, some re­searchers see a down­side.

The analy­sis, con­duct­ed by Jonathan Dar­row and oth­ers and pub­lished in JA­MA on Tues­day, found that that this evo­lu­tion has led to the FDA gen­er­al­ly ac­cept­ing less ro­bust ev­i­dence, all the while short­en­ing its re­view times.

The da­ta show that the clas­sic FDA “gold stan­dard” of ac­cept­ing new drug ap­pli­ca­tions based on at least two piv­otal tri­als has fall­en from 80.6% in 1995-1997 to 52.8% in 2015-2017. Mean­while, med­i­cines bran­dish­ing the “or­phan drug” tag — of­ten sig­nal­ing less rig­or­ous stan­dards — have risen from 18% over the pe­ri­od of 1984 to 1995 to 41% be­tween 2008 and 2018.

FDA drug re­view times have de­clined from more than 3 years in 1983 to less than 1 year in 2017 (al­though the to­tal time to get a drug ready for re­view has re­mained steady), the au­thors high­light­ed.

If drugs ap­proved with less ev­i­dence turn out to be prob­lem­at­ic it may lead to “an ero­sion of the ‘FDA ap­proved’ brand,” Dar­row told Reuters.

Joshua Sharf­stein John Hop­kins

“If the stan­dards are dif­fer­ent than they were in the past, it’s im­por­tant for pa­tients and physi­cians to be aware of that,” Dar­row said in an in­ter­view with the wire ser­vice. “Pa­tients and physi­cians need to fo­cus on the ev­i­dence and not the fact of FDA ap­proval. How big are the ben­e­fits, and how cer­tain are we of the ben­e­fits?”

While some of these new drugs have been re­mark­able ad­vances for de­bil­i­tat­ing and of­ten dead­ly dis­eases, “high prices at the high end or in ex­cess of in­de­pen­dent­ly as­sessed mea­sures of val­ue have cre­at­ed bar­ri­ers to ac­cess,” Joshua Sharf­stein from Johns Hop­kins Bloomberg School of Pub­lic Health point­ed out in a JA­MA ed­i­to­r­i­al in re­sponse to the analy­sis by Dar­row et al.

Over­all, the av­er­age an­nu­al num­ber of new drug ap­provals, in­clud­ing bi­o­log­ics, has see­sawed — from 34 be­tween 1990 and 1999 to 25 from 2000 to 2009 and 41 from 2010 to 2018, au­thors of the analy­sis found. One heart­en­ing da­ta point is the me­di­an an­nu­al num­ber of gener­ics — copy­cat ap­provals ac­cel­er­at­ed from 284 — pri­or to the Gener­ic Drug User Fee Act of 2012 — to 488 be­tween 2013 and 2018.

To ac­com­mo­date the high­er vol­ume of drug man­u­fac­tur­ers, the FDA in 1992 was grant­ed the pow­er to col­lect fees for their re­views. Now, the an­nu­al fees col­lect­ed un­der Pre­scrip­tion Drug User Fee Act (PDU­FA) have jumped from $29 mil­lion in 1993 to $908 mil­lion in 2018, the da­ta showed.

Crit­ics have ad­mon­ished the slid­ing door be­tween ex­ec­u­tives in the bio­phar­ma­ceu­ti­cal in­dus­try and the FDA, and un­der­score that the trans­ac­tion­al in­ter­ac­tion be­tween the agency and the in­dus­try does not bode well for an in­de­pen­dent, un­bi­ased re­view of prod­ucts.

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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FDA spells out the rules and re­stric­tions for states seek­ing to im­port drugs from Cana­da

The FDA is offering more of an explanation of the guardrails around its program that may soon allow states to import prescription drugs in some select circumstances from Canada, but only if such imports will result in significant cost reductions for consumers.

While the agency has yet to sign off on any of the 5 state plans in the works so far, and PhRMA’s suit to block the Trump-era rule allowing such imports is stalled, the new Q&A guidance spells out the various restrictions that states will have to abide by, potentially signaling that a state approval is coming.

David Ricks, Eli Lilly CEO (David Paul Morris/Bloomberg via Getty Images)

Eli Lil­ly set to in­vest $2.1B in home state man­u­fac­tur­ing boost

Eli Lilly is looking to expand its footprint in its home Hoosier State by making a major investment in manufacturing.

The pharma is investing $2.1 billion in two new manufacturing sites at Indiana’s LEAP Lebanon Innovation and Research District in Boone County, northwest of Lilly’s headquarters in Indianapolis.

The two new facilities will expand Lilly’s manufacturing network for active ingredients and new therapeutic modalities, including genetic medicines, according to a press release.

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US sees spike in Paxlovid us­age as Mer­ck­'s mol­nupi­ravir and As­traZeneca's Evusheld are slow­er off the shelf

New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing a streak of increased usage of the pill, and signaling not only rising case numbers but more awareness of how to access it.

In comparison to this week, about 670,000 courses of the Pfizer pill have been administered across the first five months since Paxlovid has been on the US market, averaging about 33,000 courses administered per week in that time.

Almirall is tapping artificial intelligence on behalf of its sales force for insights and efficiencies. (via Shutterstock)

Almi­rall rolls out sales rep ar­ti­fi­cial in­tel­li­gence sys­tem, cut­ting pre-call prep and 'wind­shield time'

Dermatology specialty pharma Almirall is making its sales reps smarter. Not with extra training or educational courses, but instead with artificial intelligence tools.

It began a soft launch of a sales rep AI and machine learning platform it calls Polaris last August in one of its 7 US coverage regions. The platform from Aktana gathers information from across Almirall internal sources and external ones – such as claims and prescribing data – to generate insights for reps. Now, instead of spending hours prepping for a sales call, Polaris can generate details about a physician’s preferences, past behaviors and prescription habits for reps in minutes, said Almirall head of commercial operations Vincent Cerio.

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Pfiz­er and CD­MOs ramp up Paxlovid man­u­fac­tur­ing with Kala­ma­zoo plant ex­pan­sion lead­ing the way

As the Covid-19 pandemic continues to evolve, pharma companies and manufacturers are exploring how to step up production on antivirals.

Pfizer is planning to expand its Kalamazoo-area facility to increase manufacturing capabilities for the oral Covid-19 antiviral Paxlovid, according to a report from Michigan-based news site MLive. The expansion of the facility, which serves as Pfizer’s largest manufacturing location, is expected to create hundreds of “high-skilled” STEM jobs, MLive reported. No details about the project’s cost and timeline have been released, but according to MLive, Pfizer will announce the details of the expansion at some point in early June.

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Greg Mayes, Antios Therapeutics CEO

An­tios' HBV col­lab axed af­ter clin­i­cal hold, but biotech be­lieves safe­ty in­ci­dent is not treat­ment-re­lat­ed

The FDA has placed a clinical hold on a Phase IIa study of Antios Therapeutics’ investigational hepatitis B med, CEO Greg Mayes confirmed to Endpoints News in an emailed statement.

A safety report was delivered to the biotech on May 17 after a patient dosed in a triple combination cohort of the study had experienced bradycardia and hypotension. The triple combo included Antios’ ATI-2173, Assembly Biosciences’ vebicorvir and Viread, an approved antiviral for HIV and hepatitis B.

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Tim Schoen, BioMed Realty CEO

Life sci­ences de­vel­op­er Bio­Med Re­al­ty buys San Fran­cis­co ho­tel for $75M — re­port

In a somewhat unconventional deal, life sciences real estate developer BioMed Realty has bought a 169-room Hilton Garden Inn in South San Francisco for $75 million, the San Francisco Business Times reported.

BioMed Realty, an affiliate of Blackstone, has multiple life sciences and technology office projects in the Bay Area, including three sites within a five-minute drive of the hotel.

While the sale of the hotel property was announced earlier this month, the sellers, Summit and GIC, did not identify the buyer at the time.

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Pfizer CEO Albert Bourla at the World Economic Forum (Gian Ehrenzeller/Keystone via AP Images)

All about ac­cess: Pfiz­er moves to a non-prof­it mod­el for drug sales in 45 low­er-in­come coun­tries

Leading the way to increase access to cheaper drugs worldwide, Pfizer said Wednesday it will provide all current and future patent-protected medicines and vaccines available in the US or EU on a not-for-profit basis to about 1.2 billion people in 45 lower-income countries.

Rwanda, Ghana, Malawi, Senegal and Uganda are the first five countries to sign on to this accord, which will also seek to blaze new paths for quick and efficient regulatory and procurement processes to reduce the usual delays in making new medicines and vaccines available in these countries.