No­var­tis punts a late-stage PI3K drug with a wor­ry­ing safe­ty pro­file to one of Chi­na’s up­start biotechs

Just months af­ter a group of re­searchers warned against the fur­ther de­vel­op­ment of a wor­ry­ing PI3K in­hibitor project No­var­tis had been work­ing on, the phar­ma gi­ant li­censed out the glob­al rights to a new­ly ac­tive Chi­nese biotech. 

No­var­tis is the lat­est in a long string of Big Phar­ma play­ers who have de­cid­ed to bow out of a trou­ble­some PI3K de­vel­op­ment pro­gram. But in­stead of drop­ping the drug the Swiss com­pa­ny hand­ed world­wide com­mer­cial rights to the late-stage bu­parlis­ib to one of Chi­na’s new up­start biotechs — rais­ing some thorny is­sues about how ques­tion­able drug as­sets may be passed to new play­ers for a com­mer­cial roll­out.

An­ge­lo Di Leo

Late last year a group of sci­en­tists pub­lished a re­port in The Lancet — fund­ed by No­var­tis — that con­clud­ed the drug’s safe­ty pro­file “does not sup­port its fur­ther de­vel­op­ment” in breast can­cer. The group was led by An­ge­lo Di Leo of Nuo­vo Os­pedale di Pra­to San­to Ste­fano in Pra­to, Italy.

The Chi­nese com­pa­ny is Ad­lai Nortye, based in Hangzhou. There’s no word on the terms here, but there has been a con­sid­er­able amount of mar­gin­al ef­fi­ca­cy and wor­ry­ing safe­ty da­ta on dis­play. 

In a study called Belle-3 which com­bined bu­parlis­ib with ful­ves­trant, re­searchers found that there was a pos­i­tive ben­e­fit in pro­gres­sion-free sur­vival: 3.9 months com­pared to 1.8 months for a mar­gin­al but sig­nif­i­cant ad­van­tage for pa­tients.

Grade 3/4 ad­verse events were re­port­ed in close to two out of three pa­tients in the drug arm, com­pared to 34% in the con­trol group. Se­ri­ous ad­verse events, though, were re­port­ed in 22% of the drug arm, com­pared to 16% in the con­trol group, with one treat­ment-re­lat­ed death to re­port in each arm. There were al­so three sui­cide at­tempts in the bu­parlis­ib group, rais­ing con­cerns about sui­ci­dal ideation among pa­tients ex­posed to the drug. Ruth O’Re­gan of the Uni­ver­si­ty of Wis­con­sin-Madi­son has raised con­cerns about the sui­cide at­tempts, not­ing that  “transam­i­nase el­e­va­tions and mood dis­or­ders in pa­tients on this drug may rep­re­sent a clin­i­cal­ly rel­e­vant chal­lenge.”

Ruth O’Re­gan

The re­searchers al­so not­ed in The Lancet that the work may have warned them off the drug for this set­ting, but con­clud­ed that “PI3K in­hibitors plus en­docrine ther­a­py in pa­tients with PIK3CA mu­ta­tions” is a promis­ing area of re­search.

The PI3K field has been plagued by safe­ty con­cerns and weak ef­fi­ca­cy. Roche dumped taselis­ib a few weeks ago at the end of a dis­ap­point­ing Phase III. Gilead’s pi­o­neer­ing Zy­delig got slapped with a black box warn­ing on se­ri­ous and some­times fa­tal tox­i­c­i­ties, forc­ing an end to its quest to com­plete front­line tri­als. Bay­er’s Aliqopa (co­pan­lis­ib) was ap­proved last fall for fol­lic­u­lar lym­phoma pa­tients, crowd­ing a field that Ve­rastem hopes to join with du­velis­ib, a PI3K dropped by In­fin­i­ty Phar­ma­ceu­ti­cals af­ter Ab­b­Vie walked away af­ter get­ting a glimpse of unim­pres­sive — but still ap­prov­able — re­sults. And now not­ed can­cer re­searcher Sid­dhartha Mukher­jee is be­gin­ning a hu­man study to de­ter­mine if a ke­to­genic di­et can close a feed­back loop that de­feats these drugs’ abil­i­ty to fight can­cer.

In its re­lease, Ad­lai Nortye doesn’t men­tion the breast can­cer study, or what kind of com­mer­cial prospects it has in an al­ready well de­vel­oped field. The com­pa­ny did, though, high­light “promis­ing ef­fi­ca­cy in com­bi­na­tion with pa­cli­tax­el in head and neck squa­mous cell car­ci­no­ma” and the fact that the drug “has re­ceived a Fast-Track des­ig­na­tion from the FDA.”

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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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.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.

Ver­sant-backed Chi­nook gets a $65M launch round for its dis­cov­ery quest in a resur­gent kid­ney field

Versant is once again stepping off the beaten track in biotech to see if they can blaze a trail of their own in a field that has looked too thorny to many investors for years.

The venture group and their partners at Apple Tree are bringing their latest creation out of stealth mode today. Born in Versant’s Inception Sciences’ Chinook Therapeutics is betting that its preclinical take on kidney disease can get an early lead among the companies starting up in the field.

Sir An­drew Dil­lon, NICE's first — and on­ly — chief ex­ec­u­tive to step down next year

Using a laptop borrowed from his former employer, South London’s St George’s Hospital, Sir Andrew Dillon set about establishing NICE — launched by the then health secretary Frank Dobson — in 1999.  On Thursday, the UK cost-effectiveness watchdog said its first and only chief executive — Dillon — is stepping down in March 2020.

Back in the day, decisions about which drugs and interventions were funded by the National Health Service (NHS) were made at the local level, but this ‘postcode prescribing’ system was fraught with skewed healthcare deployment making the structure unsustainable. A national system was deemed necessary — and NICE was formed to bridge that gap.