Faced with a dilem­ma, the FDA re­jects Cem­pra's an­tibi­ot­ic, de­mands big safe­ty study

Cem­pra de­liv­ered the FDA’s de­ci­sion on its an­tibi­ot­ic solithromycin on Thurs­day morn­ing, a day late and about $185 mil­lion short.

Caught on the horns of a dilem­ma posed by clear ev­i­dence of liv­er tox­i­c­i­ty and a grow­ing de­mand for new an­tibi­otics, the FDA has de­cid­ed to re­ject Cem­pra’s new an­tibi­ot­ic, de­mand­ing a large new safe­ty study be­fore re­con­sid­er­ing its po­si­tion. And the agency flagged a warn­ing that any fu­ture la­bel will care­ful­ly re­strict its use, which will dam­age its mar­ket po­ten­tial.

Cem­pra’s stock plunged 57% by the end of the day, wip­ing out about $185 mil­lion in mar­ket cap as in­vestors re­spond­ed to the worst sce­nario the biotech could have ex­pect­ed.

In a de­tailed out­line of the FDA’s CRL, Cem­pra not­ed that the agency was un­sat­is­fied by the rel­a­tive­ly small num­ber of pa­tients that had been re­cruit­ed to de­ter­mine how safe the an­tibi­ot­ic is. Reg­u­la­tors want them to aug­ment that with a study in­volv­ing 9,000 pa­tients. Cem­pra added:

The CRL not­ed that while the FDA re­serves com­ment on the pro­posed la­bel­ing un­til the NDAs are oth­er­wise ad­e­quate, even in the ab­sence of a case of Hy’s Law or of an­oth­er form of se­ri­ous DILI in fu­ture stud­ies, la­bel­ing will need to in­clude ad­e­quate in­for­ma­tion about the po­ten­tial for he­pa­to­tox­i­c­i­ty, lim­it­ing use to pa­tients who have lim­it­ed ther­a­peu­tic op­tions and lim­i­ta­tions re­gard­ing du­ra­tion of ther­a­py. A com­pre­hen­sive plan for post-mar­ket­ing safe­ty as­sess­ment in­clud­ing an en­hanced phar­ma­covig­i­lance pro­gram would al­so be re­quired.

Reg­u­la­tors al­so cit­ed man­u­fac­tur­ing is­sues in the CRL.

Cem­pra $CEMP faced a big chal­lenge go­ing in­to to­day’s an­nounce­ment. An ex­pert pan­el had of­fered its mar­gin­al sup­port with a 7-to-6 vote in fa­vor of an ap­proval. But they spent much of the day fret­ting over clear signs of tox­i­c­i­ty, which were al­so flagged in the agency’s in­ter­nal re­view. The main ques­tion at the end of the day was whether the FDA would ap­prove the an­tibi­ot­ic and then place a se­ries of pos­si­ble mar­ket-killing re­stric­tions on it or sim­ply re­ject it un­til they could get a bet­ter safe­ty pro­file.

Both the FDA and the pan­el, though, had to bal­ance their very re­al safe­ty con­cerns against a grow­ing need for new an­tibi­otics in an age of ris­ing drug re­sis­tance.

Cem­pra kept the mar­ket wait­ing for the bad news. The com­pa­ny faced two PDU­FA dates for their an­tibi­ot­ic’s oral and IV for­mu­la­tions on Tues­day and Wednes­day. The late news on the dou­ble re­jec­tion fol­lowed by the de­mand for a new tri­al and fu­ture re­stric­tions was enough to leave some an­a­lysts won­der­ing if this ther­a­py has any fu­ture at all. From Baird’s Bri­an Sko­r­ney:

At this point, we don’t see how Cem­pra moves for­ward with solithrom­cyin. The cost of run­ning a 9,000 pa­tient study with­out rev­enues from the drug to help sup­port the burn will be ex­treme­ly bur­den­some. De­spite hav­ing ~$225M in cash now, the av­er­age R&D burn in 2014-2015 was be­tween $15M and $20M per quar­ter when the Phase 3 stud­ies were be­ing run, and that’s on­ly in one-tenth the num­ber of pa­tients the FDA is ask­ing for. Fur­ther, even if ap­proved, se­vere la­bel­ing would like­ly de­ter physi­cians from us­ing it in the broad, front-line macrolide set­ting Cem­pra was hop­ing for. As a re­sult, we are low­er­ing our price tar­get to $2 on low­er prob­a­bil­i­ty of suc­cess and high­er cash burn.

Solithromycin is de­signed to work by med­dling with bac­te­r­i­al pro­tein syn­the­sis. And with a large num­ber of com­mu­ni­ty-ac­quired bac­te­r­i­al pneu­mo­nia pa­tients (CABP) re­sis­tant to the lead­ing an­tibi­ot­ic on the mar­ket, the Chapel Hill, NC-based biotech has won close at­ten­tion for its re­search work.

Cem­pra is one of just a few small biotechs which have been ad­vanc­ing late-stage an­tibi­otics in the pipeline. Nabri­va, Achao­gen and Paratek are three more play­ers in this field, while Big Phar­ma large­ly re­mains leery of a sec­tor well known for high risks and mar­gin­al pay­offs. To­day’s re­jec­tion leaves dwin­dling near-term shots at adding to the num­ber of an­tibi­otics avail­able to the pub­lic.

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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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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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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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

UP­DAT­ED: As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.