Fresh safe­ty, tol­er­a­bil­i­ty da­ta snap­shot from ear­ly-stage study of Wave's DMD drug spooks in­vestors

Wave Life Sci­ences irked in­vestors with the lat­est snap­shot of safe­ty da­ta on its ex­per­i­men­tal Duchenne mus­cu­lar dy­s­tro­phy (DMD) drug on Tues­day, caus­ing Wall Street to ques­tion whether the re­sults from the ear­ly-stage study fore­shad­owed trou­ble ahead.

The ex­per­i­men­tal drug, su­vodirsen, is be­ing test­ed in the same DMD pop­u­la­tion that Sarep­ta’s $SRPT pi­o­neer­ing Ex­ondys 51 is ap­proved to treat — boys who are amenable to ex­on 51 skip­ping. In the Phase I study, 36 pa­tients re­ceived a dose of 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, 7 mg/kg or 10 mg/kg of su­vodirsen (n=26) or place­bo (n=10) in five as­cend­ing dose co­horts and were fol­lowed for 85 days.

Re­sults from the first four co­horts (0.5 mg/kg – 5 mg/kg) showed that 16/24 pa­tients who re­ceived su­vodirsen and 8/10 pa­tients who re­ceived the place­bo ex­pe­ri­enced one or more ad­verse events of mild-to-mod­er­ate in­ten­si­ty in­clud­ing pyrex­ia, headache, vom­it­ing and tachy­car­dia.

On Tues­day, da­ta from the fifth co­hort — 2 pa­tients ad­min­is­tered with the 7 mg/kg or 10 mg/kg dose of su­vodirsen — were un­veiled. Sim­i­lar side ef­fects were re­port­ed as those ob­served at low­er dos­es, but were more se­vere in in­ten­si­ty, Wave said. The Cam­bridge, Mass­a­chu­setts-based com­pa­ny’s shares $WVE tum­bled more than 28% to close up at $24.47 on Tues­day, as in­vestors took is­sue with the drug’s tol­er­a­bil­i­ty pro­file.

Paul Mat­teis

These “ap­pear to be dose-lim­it­ing im­muno­tox­i­c­i­ties…it’s un­clear if this pro­file will get bet­ter or worse up­on re­peat dos­ing,” Stifel’s Paul Mat­teis wrote in a note.

For the piv­otal Phase II/III tri­al — ex­pect­ed to com­mence in Ju­ly 2019 — Wave has cho­sen to eval­u­ate 3.0 or 4.5 mg/kg of su­vodirsen once week­ly for 48 weeks in 150 boys. How­ev­er, an im­prove­ment in man­u­fac­tur­ing has al­lowed the com­pa­ny to arm the 4.5 mg/kg dose with the same quan­ti­ty of ac­tive in­gre­di­ent as the 5 mg/kg used in the Phase I study.

“The fact that FDA has signed off on this tri­al is a pos­i­tive, but it’s hard for us to have con­vic­tion that these dose lev­els will be suf­fi­cient,” Mat­teis added.

An­oth­er pos­si­ble stick­ing point is the com­par­i­son of su­vodirsen with Bio­Marin’s $BM­RN re­ject­ed DMD drug, dris­apersen, SVB Leerink’s Mani Foroohar wrote in a note.

Mani Foroohar

“(I)nvestors seem to see neg­a­tive read-throughs for the po­ten­tial ef­fi­ca­cy of su­vodirsen at 5 mg/kg, giv­en that dris­apersen was dosed at 6 mg/kg in clin­i­cal tri­als, we be­lieve that due to dif­fer­ences in chem­istry be­tween the com­pounds, com­par­i­son of dos­es be­tween drugs is not an ap­pro­pri­ate proxy of po­ten­tial ef­fi­ca­cy.”

Foroohar said he was main­tain­ing a 30% prob­a­bil­i­ty of suc­cess on the su­vodirsen pro­gram.

“We be­lieve we have se­lect­ed the op­ti­mal dos­es to bring for­ward in our on­go­ing open-la­bel ex­ten­sion study and planned Phase 2/3 tri­al. We look for­ward to shar­ing the dy­s­trophin re­sults from mus­cle biop­sies tak­en from the open-la­bel ex­ten­sion study in the sec­ond half of this year,” Wave chief Paul Bol­no said in an emailed state­ment.

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 with any issues.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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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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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.

FDA asks why No­var­tis took two months to launch for­mal in­ter­nal probe, af­ter AveX­is flagged da­ta ma­nip­u­la­tion

And the plot thickens. Novartis $NVS officials are reportedly now scrambling to explain to the FDA why it took them two months to open an internal investigation into data discrepancies for their $2.1 million gene-therapy for spinal muscular dystrophy — the world’s most expensive drug.

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Build­ing on suc­cess­ful PD-1 pact, Eli Lil­ly li­cens­es di­a­betes drug to Chi­nese part­ners at In­novent

Eli Lilly is expanding its partnership with China’s Innovent in a deal involving a diabetes drug sitting in its Phase I reserves.

The two companies had jointly developed one of China’s first homegrown PD-1 agents, scoring an approval for Tyvyt (sintilimab) late last year for relapsed/refractory classical Hodgkin’s lymphoma. This time around, Lilly is out-licensing a piece of its diabetes pipeline, a leading franchise that has historically produced the top-selling Trulicity and Humalog.

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.

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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