Zaf­gen has some­thing to cheer as di­a­betes drug makes the cut in PhII study

Af­ter be­ing plagued by a laun­dry list of set­backs that cul­mi­nat­ed in the de­ser­tion of its obe­si­ty drug and the de­par­ture of its CEO, Zaf­gen fi­nal­ly has some good news to re­port. Da­ta from a co­hort of a mid-stage study sug­gest­ed that its now-lead di­a­betes drug in­duced sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments in blood sug­ar lev­els and weight loss.

The Boston-based com­pa­ny’s shares $ZFGN rose about 7% in pre-mar­ket trad­ing on Thurs­day.

More than two years ago Zaf­gen aban­doned de­vel­op­ing be­lo­ranib af­ter the ex­per­i­men­tal obe­si­ty drug was linked to pa­tient deaths in a late-stage study. The FDA, wor­ried about ex­pos­ing more pa­tients to harm, slapped a clin­i­cal hold on Zaf­gen’s sec­ond-gen­er­a­tion di­a­betes drug ZGN-1061 last No­vem­ber, wary that the car­dio threat posed by be­lo­ranib was still in play. At the time, Zaf­gen said ex-US Phase II clin­i­cal tri­al of ZGN-1061 would con­tin­ue as planned, and that it would talk to the FDA staff to de­ter­mine the path for­ward.

Den­nis Kim

On Thurs­day, the com­pa­ny re­port­ed en­cour­ag­ing da­ta from the two high­est dos­es of the di­a­betes drug, fol­low­ing up on ear­li­er pos­i­tive re­sults with small­er dos­es. Ac­cord­ing to US clin­i­cal tri­als data­base, the Phase II proof-of-con­cept study in­clud­ed two groups of pa­tients. In the first co­hort, 120 pa­tients would get ei­ther 0.05, 0.3, or 0.9 mg of ZGN-1061 or place­bo, while in the sec­ond co­hort, 40 pa­tients would re­ceive 0.9 or 1.8 mg of ZGN-1061 or place­bo.

No treat­ment-re­lat­ed se­ri­ous side-ef­fects and no car­dio­vas­cu­lar safe­ty sig­nals were ob­served in the sec­ond co­hort of the study, the com­pa­ny said.

Leerink’s Joseph Schwartz did not let the com­pa­ny off the hook, how­ev­er, say­ing al­though Zaf­gen did not ob­serve any clin­i­cal­ly mean­ing­ful el­e­va­tions in mean D-dimer con­cen­tra­tions — a key bio­mark­er for CV risks — he was cau­tious ahead of phase III stud­ies in­volv­ing larg­er and het­ero­ge­neous type 2 di­a­betes pa­tient pop­u­la­tion on mul­ti­ple oth­er agents.

The com­pa­ny did not dis­close how the drug en­ters and ex­its en­dothe­lial cells, Schwartz not­ed, in ref­er­ence to con­cerns he had pre­vi­ous­ly high­light­ed re­gard­ing pre­clin­i­cal da­ta on the com­pound, which sug­gests it has the propen­si­ty to in­duce clot­ting fac­tors if it is not cleared from en­dothe­lial cells, and the po­ten­tial for drug-drug in­ter­ac­tions.

In terms of ef­fi­ca­cy, 12-week da­ta sug­gest­ed that the 1.8 mg dose sur­passed the glycemic con­trol in­duced by the 0.9 mg dose, but both dos­es con­ferred a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in A1C — a blood test that mea­sures av­er­age lev­els of blood glu­cose (p<0.0001 and p=0.0003, re­spec­tive­ly). The high­est dose caused a 1.1% re­duc­tion in A1C rel­a­tive to place­bo.

“The re­sults we’ve seen…with this lat­est 1.8 mg dose co­hort, ap­pear very com­pet­i­tive with the cur­rent­ly avail­able best-in-class an­ti-di­a­betes ther­a­pies,” Zaf­gen CMO Den­nis Kim said in a state­ment. “All of the phar­ma­co­log­i­cal ac­tions of ZGN-1061 im­prove at the 1.8 mg dose lev­el and, with its in­sulin-sen­si­tiz­ing ef­fects, we be­lieve there is a clear op­por­tu­ni­ty for even greater ben­e­fit with longer treat­ment du­ra­tion giv­en the ef­fect we are see­ing at just 12 weeks.”

Sig­nif­i­cant­ly, treat­ment with the 1.8 mg dose al­so trig­gered a place­bo-cor­rect­ed weight loss of 2.3 kg (5.1 pounds) that was sta­tis­ti­cal­ly sig­nif­i­cant (p=0.0002), Zaf­gen said, adding that there was no ev­i­dence of a wan­ing ef­fect.

“These re­sults in con­junc­tion with meta­bol­ic ben­e­fits along­side a pro­gres­sive re­duc­tion in weight po­si­tion ZGN-1061 com­pet­i­tive­ly with those agents al­ready ap­proved,” Schwartz added in a note.

Di­a­betes and obe­si­ty are close­ly linked — some drugs to treat the lat­ter have been pulled off the mar­ket due to safe­ty con­cerns, and those that have man­aged to re­main on shelves have seen mea­ger adop­tion, due to their lim­it­ed ef­fec­tive­ness, bun­gled launch­es and re­im­burse­ment hur­dles.

Last year, Zaf­gen saw big man­age­ment changes, in­clud­ing the ex­its of CEO Tom Hugh­es, who had led the com­pa­ny for 9 years, and board mem­ber Bruce Booth, who made his de­par­ture af­ter a dozen years.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.


ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology


ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development


CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources. 

As­traZeneca's di­a­betes drug Farx­i­ga helps pa­tients with heart dis­ease and with­out di­a­betes in land­mark tri­al

Months ago, data on J&J’s $JNJ Invokana indicated the diabetes drug conferred cardiovascular (CV) benefit in patients who do and do not have preexisting CV disease. On Tuesday, AstraZeneca’s $AZN rival treatment, Farxiga, was shown to cut the risk of CV death or the worsening of heart failure in patients with heart disease, in a landmark trial.

The treatments, in addition to Jardiance from Eli Lilly $LLY, belong to a class of diabetes drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors, which work by curbing the absorption of glucose via the kidneys so that surplus glucose is excreted through urination.