Zaf­gen's sec­ond try at Prad­er-Willi syn­drome trig­gers an­oth­er safe­ty alarm in pre­clin­i­cal tox study

Zaf­gen’s $ZFGN lat­est shot at cre­at­ing the first ther­a­py to treat pa­tients with rare cas­es of obe­si­ty brought on by Prad­er-Willi syn­drome has hit a safe­ty alarm be­fore the drug even man­aged to make it in­to the clin­ic.

The suc­ces­sor to be­lo­ranib — which blew up with spec­tac­u­lar ef­fect sev­er­al years ago fol­low­ing a clin­i­cal hold by the FDA — ZGN-1258 was sup­posed to be the biotech’s come­back drug in the field. In­stead, the biotech re­port­ed af­ter the mar­ket closed on Mon­day that it is sus­pend­ing plans for an IND af­ter re­searchers tracked mus­cle de­te­ri­o­ra­tion in a ro­dent mod­el of the dis­ease.

Zaf­gen’s stock shriv­eled at the men­tion of a new safe­ty alert. The shares plum­met­ed 35% af­ter the bell.

From their state­ment to­day:

Non­clin­i­cal da­ta showed de­gen­er­a­tion and oth­er anom­alies in rat mus­cle tis­sue to dif­fer­ent de­grees in both ve­hi­cle and dose arms of the stud­ies. The ef­fects were ab­sent from oth­er an­i­mal species in long term mod­els, and im­por­tant­ly, this find­ing has not been ob­served in any of the Com­pa­ny’s oth­er MetAP2 in­hibitors or clin­i­cal tri­als and ap­pears to be spe­cif­ic to ZGN-1258. Zaf­gen will pro­vide an up­date on plans for ZGN-1258 at a lat­er time, if war­rant­ed, fol­low­ing fur­ther eval­u­a­tion.

The move to shelve the IND came af­ter Zaf­gen re­port­ed in an SEC fil­ing late last year that every­thing had been lined up to ini­ti­ate clin­i­cal tri­als ex­cept for 1 last pre­clin­i­cal tri­al, which had to be re­done by a new CRO af­ter the first CRO had con­duct­ed it “im­prop­er­ly.”

Any fresh hint of a safe­ty warn­ing is tox­ic to Zaf­gen, which had to re­or­ga­nize and ul­ti­mate­ly re­place the se­nior ex­ecs who went on to oth­er en­deav­ors af­ter the first big crash. The biotech re­cent­ly re­port­ed what it called en­cour­ag­ing ear­ly da­ta about their lead drug, ZGN-1061 for obe­si­ty re­lat­ed to di­a­betes. Re­searchers re­port­ed pos­i­tive im­prove­ments in weight loss and blood sug­ar lev­els for di­a­bet­ics.

The lead drug, though, has al­so been un­der a cloud since the FDA dropped a clin­i­cal hold on the pro­gram last No­vem­ber, cit­ing CV safe­ty con­cerns. Leerink’s Joseph Schwartz has re­mained fo­cused on a key bio­mark­er for CV risk, even as the com­pa­ny pur­sued a risky ex-US tri­al.

Di­a­betes is a field with a huge pa­tient pop­u­la­tion, and even a hint of a safe­ty is­sue could prove lethal for any drug in de­vel­op­ment for this group.

And obe­si­ty drugs in gen­er­al are al­ways un­der a mi­cro­scope at the FDA, even af­ter the lat­est gen­er­a­tion hit the mar­ket, though they proved dra­mat­i­cal­ly un­suc­cess­ful as a com­mer­cial prod­uct.

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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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).

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.

Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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New play­ers are jump­ing in­to an old vac­cine game as pan­dem­ic pan­ic spreads fast — putting their tech to the test

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Roche cracks Chi­na's ADC mar­ket open as Kad­cy­la scores its first breast can­cer OK in the coun­try

Roche’s Kadcyla has become the first antibody-drug conjugate to enter the Chinese market, marking a dramatic advance for both the Swiss pharma giant and the therapeutic class.

The local arm of Roche announced the approval late Tuesday, which covers the therapy’s use in the adjuvant setting in patients with early HER-2 positive breast cancer who still have residual invasive disease after receiving paclitaxel and Herceptin as neoadjuvant treatment.

Pascal Soriot, Getty

Pas­cal So­ri­ot and As­traZeneca com­mit to car­bon neu­tral­i­ty by 2025. Where's the rest of Phar­ma?

Pascal Soriot has spent more than 20 years at the top of an industry recently found to emit more carbon than the automotive industry.

He called himself a “global citizen,” and traveled often across three-plus continents. While CEO of AstraZeneca, he commissioned a flight service — media-dubbed AstraZeneca airlines — from Cambridge to the company’s other European hub in Gothenburg. He made few, if any, public statements on the environment or his companies’ impact on it.

Fresh tri­al da­ta for­ti­fy po­si­tion of Roche's oral ther­a­py in spinal mus­cu­lar at­ro­phy bat­tle­ground

With an FDA decision date looming, Roche on Wednesday unveiled positive pivotal data on its blockbuster-bound oral spinal muscular atrophy (SMA) drug in patients with the most severe form of the muscle-wasting disease.

The FDA is set to make its decision on the therapy, risdiplam, by May 24. It is expected to compete with Biogen’s Spinraza and Novartis’ Zolgensma.

Partnered with PTC Therapeutics, the Roche drug was tested in 41 patients aged 1-7 months with type 1 SMA, a rare genetic muscle-wasting disease. The trial, dubbed FIREFISH, measured efficacy via the proportion of infants sitting without support after 12 months of treatment, and longer.

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.