JJ Bienaimé, BioMarin CEO (Via YouTube)

New da­ta show Bio­Mar­in's trou­bled he­mo­phil­ia gene ther­a­py con­tin­ues to fade, open­ing room for ri­vals

The ef­fects of Bio­Marin’s vaunt­ed gene ther­a­py for he­mo­phil­ia A are con­tin­u­ing to fade in the ear­li­est treat­ed pa­tients, re­new­ing ques­tions about the long-term prospects for a drug the com­pa­ny had billed as a one-time cure.

At the In­ter­na­tion­al So­ci­ety on Throm­bo­sis and Haemosta­sis meet­ing Wednes­day, Bio­Marin an­nounced that, af­ter five years, the first sev­en pa­tients treat­ed with the ther­a­py’s high dose ex­pressed a me­di­an of just 8.2% the amount of fac­tor VI­II that a healthy per­son would. That’s a small frac­tion of the 60.3% ex­pres­sion pa­tients saw one year af­ter re­ceiv­ing the ther­a­py, known as val­rox.

Bio­Marin high­light­ed — as they have be­fore — that de­spite the wan­ing lev­els of pro­tein, pa­tients were still large­ly symp­tom-free. The ther­a­py re­duced the an­nu­al­ized bleed­ing rate by 95% among six of the pa­tients, and even in year 5, six of the sev­en pa­tients had no bleed­ing events at all.

He­mo­phil­ia A pa­tients are miss­ing a func­tion­al copy Fac­tor VI­II, a clot­ting pro­tein es­sen­tial for stop­ping bleed­ing. But as with sick­le cell and many ge­net­ic dis­eases now be­ing tar­get­ed by gene ther­a­pies, re­searchers don’t ac­tu­al­ly have to get pa­tients to com­plete nor­mal ex­pres­sion in or­der to al­le­vi­ate symp­toms and al­low peo­ple to lead healthy lives; of­ten a frac­tion will do.

Pre­cise­ly how large a frac­tion, though, re­mains un­known, and Bio­Marin’s dwin­dling lev­els have raised flags with reg­u­la­tors. Last year, in a sur­prise move, the FDA re­ject­ed the com­pa­ny’s ap­pli­ca­tion for ap­proval, say­ing they would need to see more dura­bil­i­ty da­ta be­fore al­low­ing Bio­Marin to put the drug on the mar­ket.

Dura­bil­i­ty is a greater con­cern with mod­ern gene ther­a­pies than it is for oth­er med­i­cines. Pa­tients can on­ly be dosed once, giv­ing re­searchers on­ly a sin­gle shot to cure the dis­ease. And the com­pa­ny’s CEO JJ Bi­en­aimé has promised to price val­rox as if it were a cure: be­tween $2 mil­lion and $3 mil­lion per year.

The new da­ta, though, show that gene ex­pres­sion has steadi­ly de­clined year-to-year, un­der­scor­ing con­cerns that it could one day drop be­low lev­els that are ther­a­peu­ti­cal­ly rel­e­vant and keep pa­tients off of trans­fu­sions.

Those fears may not pre­vent Bio­Marin from ob­tain­ing ap­proval. The com­pa­ny ex­pects to have two-year da­ta from its Phase III tri­al in ear­ly 2022, at which point they would like­ly re­file with the FDA.

It could, how­ev­er, dras­ti­cal­ly di­min­ish the ther­a­py’s ben­e­fit for pa­tients and how much mon­ey Bio­Marin can make. With oth­er he­mo­phil­ia A gene ther­a­pies al­so near­ing ap­proval, pa­tients may wait for some­thing that looks clos­er to a one-time cure.

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

15 LGBTQ lead­ers in bio­phar­ma; Paul Stof­fels’ Gala­pa­gos re­vamp; As­traZeneca catch­es up in AT­TR; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

A return to in-person conferences also marks a return to on-the-ground reporting. My colleagues Beth Synder Bulik and Nicole DeFeudis were on-site at Cannes Lions, bringing live coverage of pharma’s presence at the ad festival — accompanied by photos from Clara Bui, our virtual producer, that bring you right to the scene. You can find a recap (and links to all the stories) below.

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David Loew (Ipsen)

Ipsen snags an ap­proved can­cer drug in $247M M&A deal as an­oth­er bat­tered biotech sells cheap

You can add Paris-based Ipsen to the list of discount buyers patrolling the penny stock pack for a cheap M&A deal.

The French biotech, which has had plenty of its own problems to grapple with, has swooped in to buy Epizyme $EPZM for $247 million in cash and a CVR with milestones attached to it. Epizyme shareholders, who had to suffer through a painfully soft launch of their EZH2a inhibitor cancer drug Tazverik, will get $1.45 per share along with a $1 CVR tied to achieving $250 million in sales from the drug over four consecutive quarters as well as an OK for second-line follicular lymphoma by 1 Jan. 2028.

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AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

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GSK says its drug for chron­ic hep B could ‘lead to a func­tion­al cure’ — but will it be alone or in com­bi­na­tion?

GSK, newly branded and soon-to-be demerged, shared interim results from its Phase II trial on its chronic hepatitis B treatment, one that it says has the “potential to lead to a functional cure.”

At a presentation at the EASL International Liver Congress, GSK shared that in around 450 patients who received its hep B drug bepirovirsen for 24 weeks, just under 30% had hepatitis B surface antigen and viral DNA levels that were too low to detect.

Sanofi, GSK tout 72% Omi­cron ef­fi­ca­cy in PhI­II tri­al of next-gen, bi­va­lent shot — with an eye to year-end roll­out

Sometimes, being late can give you an advantage.

That’s what Sanofi and GSK are trying to say as the Big Pharma partners report positive results from a late-stage trial of their next-gen bivalent Covid-19 vaccine, which was designed to protect against both the original strain of the SARS-CoV-2 virus and the Beta variant. Specifically, against Omicron, they note, the vaccine delivered 72% efficacy in all adults and 93.2% in those previously infected.

Matt Kapusta, uniQure CEO

In trou­bled Hunt­ing­ton’s space, uniQure’s gene ther­a­py shows ear­ly promise

In randomized clinical trial data from a small number of patients, Dutch biotech uniQure shared that its gene therapy for Huntington’s disease seems to reduce the amount of the mutant protein responsible for the disease over the course of a year.

In seven patients with early-stage Huntington’s — four who got the treatment and three who got a placebo — mutant huntingtin protein levels in the cerebrospinal fluid decreased by an average of just over 50% in patients who got the gene therapy compared to around a 17% drop in patients who got the placebo after a year.

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De­spite a slow start to the year for deals, PwC pre­dicts a flur­ry of ac­tiv­i­ty com­ing up

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

Abortion-rights protesters regroup and protest following Supreme Court's decision to overturn Roe v. Wade. (AP Photo/Gemunu Amarasinghe)

Fol­low­ing SCO­TUS de­ci­sion to over­turn abor­tion pro­tec­tions, AG Gar­land says states can't ban the abor­tion pill

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”