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.

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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Step­ping on Roche's toes, Mer­ck cuts in­to SCLC niche with third-line Keytru­da OK

In the in­creas­ing­ly crowd­ed check­point race, small cell lung can­cer has been a rare area where Roche, a sec­ond run­ner-up, has a lead over the en­trenched lead­ers Mer­ck and Bris­tol-My­ers Squibb. But Mer­ck is fi­nal­ly mak­ing some head­way in that di­rec­tion with the lat­est ap­proval for its PD-1 star.

The lat­est green light en­dors­es Keytru­da in the third-line treat­ment of metasta­t­ic SCLC, where it would be giv­en to pa­tients whose dis­ease ei­ther don’t re­spond to or re­lapse af­ter chemother­a­py, which would have fol­lowed at least one pri­or line of ther­a­py.

Image: Shutterstock

Gene ther­a­py R&D deals turn red hot as Big Phar­ma steps up to play

This September will mark the 20th anniversary of the death of Jesse Gelsinger, a young man suffering from X-linked genetic disease of the liver. He was killed in a gene therapy study conducted by Penn’s James Wilson, and the entire field endured a lengthy deep freeze as the field grappled with the safety issues inherent in the work.

Some thought gene therapy R&D would never survive. But it did. And this year marked a landmark approval for Zolgensma, a new gene therapy for spinal muscular atrophy Novartis priced at $2.1 million.

“Gene therapy is the hottest item on the block now. But there was a time when we first got into this trial, where there wasn’t a person in the world who believed that gene therapy would work. We have to remember that,” noted gene therapy investigator Jerry Mendell told SMA News Today.

We’re still right on the pioneering frontier when it comes to getting approvals for gene therapies and launching marketing campaigns with the European green light for bluebird's leading program last Friday underscoring the nascent nature of the field. But gene therapy R&D is booming, and has been for several years now.

The rapid growth of gene therapy clinical development is well known, but we decided to put some numbers on it, to quantify what’s going on. DealForma chief Chris Dokomajilar took a lot over the past 10 years, as the number of deals, R&D partnerships and buyouts steadily gained steam, spiking last year and on track to maintain the surge in 2019.

The upfronts and totals for the dollars on deals so far in 2019 is already close to the 2018 mark, underscoring a new phase of negotiations as the major players step up to gain a piece of the late-stage and commercial action.

Once again, we’re looking at an “overnight” biotech success story, decades in the making.

At some point, that may start to brake the numbers we’re seeing. But for now, as rivals line up to compete for frontline prominence across a range of diseases, the arrows are all pointed north.

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Albert Bourla appears before the Senate Committee on Finance for a hearing on prescription drug pricing on Capitol Hill in Washington, DC, February 26, 2019. Chris Kleponis for CNP via AP Images

UP­DAT­ED: Pfiz­er CEO Al­bert Bourla is back in the M&A game, but why is he pay­ing $11.4B for Ar­ray?

Pfiz­er $PFE has cut short its time on the side­lines of bio­phar­ma M&A.

Mon­day morn­ing the phar­ma gi­ant un­veiled an $11.4 bil­lion deal to ac­quire Ar­ray Bio­Phar­ma, beef­ing up its on­col­o­gy work and adding a new re­search hub in Boul­der, Col­orado to its glob­al op­er­a­tions.

At $48 a share, Ar­ray $AR­RY in­vestors will be get­ting a 62% pre­mi­um off the Fri­day close of $29.59.

Pfiz­er, which has strug­gled to gain all the up­side promised in past buy­outs like Medi­va­tion, high­light­ed the ac­qui­si­tion of 2 ap­proved drugs in the deal — Braftovi (en­co­rafenib) and Mek­tovi (binime­tinib).

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Right back at you, Pfiz­er: BeiGene and a Pfiz­er spin­out launch a new­co to de­vel­op a MEK/BRAF in­hibitor that could ri­val $11.4B com­bo

A day af­ter Pfiz­er bought Ar­ray and its ap­proved can­cer com­bo, BeiGene and Pfiz­er spin­out Spring­Works have part­nered in launch­ing a new biotech that has an eye on the very same mar­ket the phar­ma gi­ant just paid bil­lions for. And they’re plan­ning on us­ing an ex-Pfiz­er drug to do it.

In a nut­shell, Chi­na’s BeiGene is toss­ing in a pre­clin­i­cal BRAF in­hibitor — BGB-3245, which cov­ers both V600 and non-V600 BRAF mu­ta­tions — for a big stake in a new, joint­ly con­trolled biotech called Map­Kure with Bain-backed Spring­Works.

Sanofi aligns it­self with Google to stream­line drug de­vel­op­ment

Tech­nol­o­gy is bleed­ing in­to health­care, and big phar­ma is rid­ing the wave. Sanofi $SNY ap­point­ed its first chief dig­i­tal of­fi­cer this Feb­ru­ary, fol­low­ing the foot­steps of its peers. By May, the French drug­mak­er and some of its big phar­ma com­pa­tri­ots joined forces with Google par­ent Al­pha­bet’s Ver­i­ly unit to aug­ment clin­i­cal tri­al re­search. On Tues­day, the Parisian com­pa­ny tied up with Google to ac­cess its cloud com­put­ing and ar­ti­fi­cial in­tel­li­gence tech to spur the de­vel­op­ment of new ther­a­pies.

Af­ter watch­ing its share price soar on a Bloomberg re­port and heat­ed ru­mors, Bio­haven stock takes a bil­lion-dol­lar bath

Back in April, Biohaven Pharmaceutical became one hot biotech stock $BHVN based on a report in Bloomberg that some “potential bidders” had been kicking the tires at the biotech, which has a lead drug for migraines. Then the rumor mill really started to smoke when execs canceled a presentation at an investor conference a little more than a week ago.

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UP­DAT­ED: Roche fields first ap­proval for Ro­z­lytrek in the run-up to a show­down with Bay­er, Pfiz­er

While it’s wait­ing to hear back from FDA reg­u­la­tors, Roche is be­gin­ning the vic­to­ry lap for en­trec­tinib in Japan.

Roche is giv­ing Bay­er a run for their mon­ey with this tu­mor-ag­nos­tic drug, which tar­gets NTRK gene fu­sions. Now dubbed Ro­z­lytrek, it’s sanc­tioned to treat adult and pe­di­atric pa­tients in Japan with neu­rotroph­ic ty­ro­sine re­cep­tor ki­nase fu­sion-pos­i­tive, ad­vanced re­cur­rent sol­id tu­mors.

A uni­corn stalks Wall Street in search of IPO cash; CASI Phar­ma in-li­cens­es CD19 ther­a­py from Chi­na’s Ju­ven­tas

→ A herd of up­start biotechs will look to Wall Street for some ma­jor wind­falls this week as a burst of new of­fer­ings con­tin­ues to feed cash in­to the R&D sys­tem. To­day we learned that Bridge­Bio will look to raise in the neigh­bor­hood of $225 mil­lion by of­fer­ing 15 mil­lion shares for $14 to $16 each. And they have a string of joint bookrun­ners: J.P. Mor­gan, Gold­man Sachs, Jef­feries, SVB Leerink, KKR, Piper Jaf­fray, Mizuho Se­cu­ri­ties, BMO Cap­i­tal Mar­kets and Ray­mond James. If suc­cess­ful, Bridge­Bio will emerge with a mar­ket cap of around $1.7 bil­lion. There are 5 biotechs look­ing to IPO this week, in­clud­ing Akero and Pre­vail.