FDA rushed to ap­prove new drugs in 2019, some­times way ahead of sched­ule. Could that be dan­ger­ous?

While the ros­ter of 48 drugs (plus 4 no­table bi­o­log­ics) the FDA ap­proved in 2019 didn’t break any records with the sheer num­ber it was re­mark­able in one as­pect: The agency reached deep in­to a group of ther­a­pies they didn’t need to make a de­ci­sion on un­til lat­er this year, in some cas­es speed­ing drugs up by months ahead of even pri­or­i­ty re­view dead­lines.

On the sur­face, that’s great news for drug­mak­ers and the pa­tients they hope to help. But ac­cord­ing to a re­cent study on rushed ap­provals, it could al­so spell safe­ty trou­bles down the road.

Lau­ren Co­hen

Back in Ju­ly, a trio of econ­o­mists at NBER crunched the da­ta on drugs OK’d be­fore sup­posed dead­lines such as the end of months, years or be­fore hol­i­days and found that treat­ments ap­proved un­der these ap­par­ent “desk-clear­ing” ef­forts — in which reg­u­la­tors felt the pres­sure of in­for­mal per­for­mance bench­marks — are more like­ly to be as­so­ci­at­ed with post­mar­ket safe­ty is­sues.

“We see about twice as many ad­verse ef­fects,” Lau­ren Co­hen, a pro­fes­sor of fi­nance and en­tre­pre­neur­ial man­age­ment at Har­vard Busi­ness School and one of the au­thors, told the Wall Street Jour­nal.

Co­hen and his col­leagues, Umit Gu­run of the Uni­ver­si­ty of Texas at Dal­las and Danielle Li of MIT, con­sid­ered on­ly the surge of ap­provals in De­cem­ber, at the end of each month and be­fore hol­i­days such as Thanks­giv­ing.

In 2019 sev­en out of 48 nov­el chem­i­cal en­ti­ties were ap­proved in De­cem­ber, large­ly in line with the 15% pro­por­tion that the re­searchers not­ed in pre­vi­ous years. But no­tably, 21 OKs came through in Q4, ac­count­ing for 43% of the whole crop.

FDA spokesper­son Nathan Arnold ac­knowl­edged the De­cem­ber jump pat­tern but told the Jour­nal that its share has ac­tu­al­ly di­min­ished from the 1980s.

“While we can­not speak di­rect­ly to the re­sults on in­for­mal dead­lines high­light­ed in this study, FDA has—on mul­ti­ple oc­ca­sions—in­ves­ti­gat­ed a close­ly re­lat­ed is­sue, which is the re­la­tion­ship be­tween for­mal PDU­FA dead­lines and post­mar­ket safe­ty of drugs,” Arnold added. “We have not found ev­i­dence of such a re­la­tion­ship.”

Drugs that ap­peared to have been ap­proved with lit­tle heed of the PDU­FA dead­lines might be an­oth­er is­sue. Ver­tex’s Trikaf­ta (for cys­tic fi­bro­sis), BeiGene’s Brukin­sa (for man­tle cell lym­phoma), No­var­tis’ Adakveo and Glob­al Blood Ther­a­peu­tics’ Oxbry­ta (for sick­le cell dis­ease), as well as Al­ny­lam’s Givlaari (for acute he­pat­ic por­phyr­ia ) and As­traZeneca/Dai­ichi Sankyo’s En­her­tu (for HER+ breast can­cer) all be­longed to that group.

Co­hen, Gu­run and Li pre­scribed a so­lu­tion for the safe­ty con­cerns they spot­ted:

A po­ten­tial pol­i­cy re­sponse to the pat­terns we doc­u­ment is to more care­ful­ly scru­ti­nize drugs that are ap­proved dur­ing such out­put surges. Reg­u­la­tors could, for in­stance, re­view end-of-year de­ci­sions in the fol­low­ing year be­fore pro­vid­ing an ul­ti­mate ap­proval (or lack there­of).

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Wuhan virus out­break trig­gers in­evitable small-biotech ral­ly

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

Brex­it fears, Wood­ford woes over­shad­owed UK biotech and cut 2019 fi­nanc­ing by al­most half

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

Blue­print Med­i­cines po­ten­tial­ly de­lays Ay­vak­it de­ci­sion; Con­trol beats treat­ment in mesothe­lioma tri­al

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III Voyage trial before they give a judgment.

Io­n­is, Akcea boost­ed by a pos­i­tive PhII for their No­var­tis castoff car­dio drug — and they plan to push ahead in­to piv­otals

Late last year Novartis abandoned a cardio drug from Ionis’ spinoff Akcea just after the pharma giant snapped up inclisiran, going the RNAi way in guarding against heart disease in the $9.7 billion Medco buyout.

Now the pharma goliath — which is headed down the PCSK9 road with a drug it believes can be used in a mass population — can get a clearer picture of just what they gave up.

Akcea $AKCA and the mother company $IONS put out a statement early Wednesday saying that their Phase II study of AKCEA-APOCIII-LR delivered solid efficacy data, with the high dose clearly outperforming placebo in significantly reducing triglycerides as a means to cutting the risk of cardiovascular disease. In addition, investigators concluded that the drug slashed apoC-III, very low-density lipoprotein and remnant cholesterol while boosting “good” HDL levels.

Hal Barron and Emma Walmsley, GSK

GSK’s ‘break­through’ BC­MA can­cer drug gets a pri­or­i­ty re­view — and a big win for the on­col­o­gy R&D team

After largely whiffing the past 2 years on the pharma R&D front, GlaxoSmithKline research chief Hal Barron has seized boasting rights to a key win that puts them back in the cancer drug development game.

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.