Pa­tients of­ten de­mand ex­per­i­men­tal drugs that prove in­ef­fec­tive — re­port

A new pa­per by a team of FDA of­fi­cials finds that on­ly about 30% of drugs re­quest­ed for ex­pand­ed ac­cess go on to be ap­proved by the agency.

“Ex­pand­ed ac­cess pro­vides just that: ac­cess. There is no guar­an­tee that the prod­uct sought will be ef­fec­tive and/or safe, much less that it will be ef­fec­tive and/or safe for the par­tic­u­lar pa­tient,” the au­thors write.

Back­ground

In re­cent years, the de­bate over pa­tient ac­cess to un­ap­proved drugs has risen to the na­tion­al stage. So called “right-to-try” laws, al­so known as right-to-ask laws, seek to by­pass FDA to pro­vide ac­cess to un­ap­proved drugs and have been en­act­ed in 37 states. In Au­gust, the US Sen­ate passed a bill that would ex­pand right-to-try na­tion­wide, though the House has yet to con­sid­er the bill.

The de­bate fo­cus­es on a pa­tient’s right to ac­cess un­ap­proved drugs to treat se­ri­ous or life-threat­en­ing dis­eases out­side of a clin­i­cal tri­al. Pro­po­nents of right-to-try have ar­gued that FDA is a bar­ri­er to pa­tient ac­cess, while FDA has coun­tered that it ap­proves near­ly all re­quests for ac­cess it re­ceives.

Un­der FDA’s ex­pand­ed ac­cess pro­gram, physi­cians can re­quest ac­cess to a drug for in­di­vid­ual pa­tients or a group of pa­tients un­der an ex­pand­ed ac­cess in­ves­ti­ga­tion­al new drug ap­pli­ca­tion (IND) or via a new pro­to­col un­der an ex­ist­ing IND.

While FDA main­tains that clin­i­cal tri­als are the best op­tion for pa­tients to get ac­cess to un­ap­proved drugs, the agency ac­knowl­edges that it’s not al­ways pos­si­ble for a pa­tient to en­roll in a clin­i­cal tri­al.

FDA has al­so said that in most cas­es phar­ma­ceu­ti­cal com­pa­nies de­ny re­quests for ex­pand­ed ac­cess, of­ten cit­ing sup­ply or safe­ty con­cerns. Right-to-try pro­po­nents have coun­tered that drug­mak­ers turn down such re­quests out of fear that ad­verse events that oc­cur be­cause of ex­pand­ed ac­cess use could de­rail their de­vel­op­ment pro­grams or open the com­pa­ny up to oth­er li­a­bil­i­ty is­sues.

Ex­pand­ed Ac­cess and Ap­proval

Ac­cord­ing to the au­thors, FDA re­ceived 6,054 unique ex­pand­ed ac­cess re­quests be­tween FY2010 and FY2014. Af­ter ex­clud­ing ex­pand­ed ac­cess re­quests for mul­ti­ple pa­tients and clean­ing the re­sults for du­pli­cate and “non­sub­mit­ted” INDs, the au­thors were left with 5,394 unique re­quests, 5,298 of which were al­lowed to pro­ceed.

Of those, the au­thors were able to iden­ti­fy 408 unique drugs and fixed-dose com­bi­na­tions.

By 30 Sep­tem­ber 2015, 122 (30%) of those drugs had been ap­proved by the agency for at least one in­di­ca­tion, though not nec­es­sar­i­ly for the in­di­ca­tions sought in ex­pand­ed ac­cess re­quests.

Six of the top ten most-re­quest­ed drugs went on to be ap­proved, though the pa­per does not men­tion the names of those drugs be­cause of con­fi­den­tial­i­ty rea­sons.

Look­ing at it from an­oth­er di­rec­tion, 3,365 of the 5,298 re­quests were for drugs that lat­er went on to be ap­proved, with a hand­ful of drugs ac­count­ing for a large pro­por­tion of those re­quests.

The au­thors al­so found lit­tle ev­i­dence to sup­port the ar­gu­ment that ad­verse events that oc­cur as a re­sult of ex­pand­ed ac­cess treat­ment can jeop­ar­dize a drug de­vel­op­ment pro­gram.

“Over the last decade, span­ning al­most 11,000 ex­pand­ed ac­cess re­quests, there were on­ly 2 in­stances in which a clin­i­cal hold was placed on com­mer­cial drug de­vel­op­ment due to ad­verse events oc­cur­ring un­der ex­pand­ed ac­cess. In both in­stances the de­vel­op­ment of the drugs con­tin­ued af­ter these is­sues were ad­dressed and the holds were lift­ed,” the au­thors write.

And the au­thors cast doubt on the ar­gu­ment that li­a­bil­i­ty con­cerns keep drug­mak­ers from pro­vid­ing ex­pand­ed ac­cess to their prod­ucts. A search of three le­gal data­bas­es, Google Schol­ar and HeinOn­line turned up no re­sults for prod­uct li­a­bil­i­ty suits against drug­mak­ers for per­son­al in­juries as a re­sult of ex­pand­ed ac­cess treat­ment.


First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion.

Albert Bourla, Pfizer CEO (John Thys/POOL/AFP via Getty Images)

Pfiz­er CEO un­der fire from UK watch­dog over vac­cine com­ments — re­port

Pfizer CEO Albert Bourla told the BBC last December that he had “no doubt in my mind that the benefits, completely, are in favor” of vaccinating 5- to 11-year-olds for Covid-19. Almost a year later, those comments have reportedly landed him in trouble with a UK pharma watchdog.

Children’s advocacy group UsForThem filed a complaint with the UK’s Prescription Medicines Code of Practice Authority (PMCPA) last year accusing Bourla of making “disgracefully misleading” statements during the BBC interview, including one that “Covid in schools is thriving.” At the time, UK regulators had not yet cleared the vaccine for the 5 to 11 age group, though the vaccine did have a positive opinion from the EMA’s human medicines committee.

FDA tells Catal­ent to fix is­sues at two man­u­fac­tur­ing sites on its own

The CDMO Catalent will have to fix issues at two manufacturing plants in the US and Europe that were subject to inspections by the FDA this summer, giving the company room to correct the issues without facing further regulatory action.

The FDA gave Catalent a “voluntary action indicated” response to two inspections at the contract manufacturer’s site in Bloomington, IN, and Brussels, Belgium. Fixing the issues on its own is a preferable outcome to facing an “official action indicated” response, meaning that an official warning would be sent out or a sit-down with the FDA would be required.

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Sanofi's new headquarters, La Maison Sanofi, in Paris (Credit: Luc Boegly)

Sanofi wel­comes 500 staffers to new Paris HQ af­ter €30M ren­o­va­tion

When Paul Hudson took the helm at Sanofi back in 2019, he promised to reinvent the pharma giant — including its Paris headquarters. This week, the company set up shop in new “state-of-the-art” digs.

La Maison Sanofi, as the new HQ is called, is officially open for business, Hudson announced on Monday. The 9,000-square-meter (just under 97,000-square-foot) space accommodates 500 employees across the company’s government and global support functions teams, including finance, HR, legal and corporate affairs — and it was built with environmental sustainability and hybrid work in mind.

Sta­da to place $50M+ in­vest­ment in a new fa­cil­i­ty in Ro­ma­nia

While Romania may conjure up images of vast mountain ranges and tales of medieval kings, one generic manufacturer has broken ground on a new facility there.

German pharma company Stada said Monday that it has placed a €50 million ($51.9 million) investment into a 100,000 square-meter (1.08 million square-foot) site in Turda, Romania, a city in the Southeast of the country. According to a Stada spokesperson in an email to Endpoints News, the company has developed only 281,500 square feet of the site so far.

Rachael Rollins (Charles Krupa/AP Images)

US seeks jail time for co-CEO of New Eng­land com­pound­ing cen­ter af­ter dead­ly 2012 fun­gal out­break

The US attorney for the district of Massachusetts late last week called on the state’s district court to sentence the former co-owner of the now-defunct New England Compounding Center to 18 months of jail time for his role in the center’s quality deviations that led to more than 100 people dead from a fungal meningitis outbreak.

Gregory Conigliaro was convicted of conspiring with more than a dozen others at NECC to deceive the FDA and misrepresent the fact that the center was only dispensing drugs pursuant to patient-specific prescriptions.

Vac­cine doc­u­ments, young lead­ers and mar­ket tur­moil: End­points' 10 biggest sto­ries of 2022

It’s been a volatile year in the world of biopharma. Market declines reset M&A valuations, and may be beginning to tempt bigger buyers back into dealmaking. Russia’s war in Ukraine disrupted drug sales and clinical trials. A new generation of young biotech leaders emerged in the Endpoints 20(+1) Under 40. And as capital runs dry in a tough environment for raising new funds, companies big and small are taking a look at their headcounts and operations for ways to make it through lean times.

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Tom Riga, Spectrum Pharmaceuticals CEO

Spec­trum im­plodes af­ter a harsh pub­lic slap­down and now a CRL from Richard Paz­dur

The FDA has gone out of its way several times to flatten any expectations for Spectrum’s lung cancer drug poziotinib, including slamming the regulatory door in the biotech’s face four years ago when the their executive crew came calling for a breakthrough drug designation and encouragement from the oncology wing of the FDA.

That stinging early rebuke pointed straight down the path to a corrosive in-house agency review of Spectrum’s attempt to land an accelerated approval for the oral EGFR TKI and a public whipping that included a classic takedown by none other than Richard Pazdur, who slammed the company for “poor drug development” that led to confusion over the dose needed for a slice of NSCLC patients harboring HER2 exon 20 insertion mutations.

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Merck targets vaccine-hesitant parents in its latest 'Why Vaccines' campaign. (Image: Shutterstock)

Mer­ck­'s lat­est 'Why Vac­ci­nes' cam­paign seeks to bet­ter in­form vac­cine-hes­i­tant moms

From Hollywood couple endorsements to targeted equity efforts, Merck has been pushing the value of vaccinations, especially since the Covid-19 pandemic disruption. Now the pharma is turning to a new target — vaccine-hesitant parents, and moms in particular.

Merck’s “Why Vaccines” latest social media and digital campaign spotlights real-life new moms who have questions about vaccinating their children.

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Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

As you start planning for #JPM23, we hope you will consider joining Endpoints News for our live and virtual events. For those who are celebrating Thanksgiving, we hope you are enjoying the long weekend with loved ones. And if you’re not — we’ll see you next week!

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