Shares of As­traZeneca $AZN start­ed to slide this morn­ing as the phar­ma gi­ant con­firmed that the FDA has placed a par­tial clin­i­cal hold on a Phase III re­search pro­gram in­volv­ing its check­point in­hibitor dur­val­um­ab, halt­ing new en­roll­ment.

The par­tial hold was in­sti­tut­ed af­ter in­ves­ti­ga­tors tracked bleed­ing events in a Phase III com­bo study for dur­val­um­ab, its top in­ves­ti­ga­tion­al drug, with treme­li­mum­ab for head and neck can­cer. But the com­pa­ny cau­tions that all oth­er stud­ies are pro­ceed­ing as planned, not­ing that such bleed­ing events are not un­usu­al in head and neck can­cer.

That said, As­traZeneca can ill af­ford any de­lays in the de­vel­op­ment of dur­val­um­ab now. The com­pa­ny al­ready de­layed its de­vel­op­ment time­line for the check­point in­hibitor to al­low for com­bi­na­tion stud­ies, which As­traZeneca is count­ing on to make a splash with a late ar­rival in the field.

A set­back here will raise fresh ques­tions for As­traZeneca as it at­tempts to play catch-up to the mar­ket lead­ers in check­point in­hibitors. Dur­val­um­ab is now a dis­tant fourth — or fifth — in the mar­ket, like­ly to fol­low Roche’s $RHH­BY Tecen­triq and well be­hind Mer­ck ($MRK/Keytru­da) and Bris­tol-My­ers Squibb $BMY, which has racked up block­buster sales with Op­di­vo.

As­traZeneca’s shares are down 5%.

The news about the safe­ty is­sue has been per­co­lat­ing in­side As­traZeneca for more than a month.

In a fol­lowup to a query, As­traZeneca said that they took the first step in paus­ing en­roll­ment in mid-Sep­tem­ber, more than a month ago, then fol­lowed up with no­tices to reg­u­la­tors and in­ves­ti­ga­tors. Ac­cord­ing to a spokesper­son:

The FDA re­cent­ly con­firmed their agree­ment with our ac­tion and placed a par­tial clin­i­cal hold on re­cruit­ment of new pa­tients while we com­plete our analy­sis. We sent an up­date to Clin­i­cal­Tri­als.gov with­in the usu­al time­frames. Our analy­sis is now com­plete and has been sub­mit­ted to FDA and un­der their re­view; we hope to re­sume [en­roll­ment] as soon as pos­si­ble.

$AZN let's not for­get that both IO drugs are as­so­ci­at­ed w/ col­i­tis/gut per­fo­ra­tions so to­geth­er could lead to more bleed­ing in­ci­dences

— Sal­ly Church 🏴󠁧󠁢󠁥󠁮󠁧󠁿 (@Mav­er­ick­NY) Oc­to­ber 27, 2016

Here’s the full ini­tial state­ment sent to End­points News:

Fol­low­ing the re­cent up­date on clin­i­cal­tri­als.gov, As­traZeneca con­firms that the US FDA has placed a par­tial clin­i­cal hold on the en­roll­ment of new pa­tients with head and neck squa­mous cell car­ci­no­ma (HN­SCC) in clin­i­cal tri­als of dur­val­um­ab as monother­a­py and in com­bi­na­tion with treme­li­mum­ab or oth­er po­ten­tial med­i­cines. All tri­als are con­tin­u­ing with ex­ist­ing pa­tients.

The par­tial clin­i­cal hold on new pa­tient [en­roll­ment] re­lates on­ly to head and neck can­cer. Tri­als for dur­val­um­ab in dif­fer­ent can­cer types, as monother­a­py or in com­bi­na­tion with treme­li­mum­ab or oth­er po­ten­tial med­i­cines, are pro­gress­ing as planned, with piv­otal da­ta in lung can­cer an­tic­i­pat­ed in the first half of 2017.

The FDA’s de­ci­sion fol­lows vol­un­tary ac­tion by As­traZeneca to pause [en­roll­ment] of new HN­SCC pa­tients while a de­tailed analy­sis is con­duct­ed of ad­verse events re­lat­ed to bleed­ing that were ob­served as part of rou­tine safe­ty mon­i­tor­ing of the Phase III KESTREL and EA­GLE tri­als. Bleed­ing is a known com­pli­ca­tion in treat­ments of head and neck can­cers pri­mar­i­ly due to the na­ture of the un­der­ly­ing dis­ease, the prox­im­i­ty of tu­mours to ma­jor blood ves­sels and use of pri­or can­cer ther­a­pies, which may in­volve surgery and ra­di­a­tion.

As­traZeneca has sub­mit­ted its analy­sis of the ob­served bleed­ing events to the FDA for re­view and is work­ing close­ly with the Agency, pro­vid­ing the re­quired in­for­ma­tion to re­sume new pa­tient [en­roll­ment] as soon as pos­si­ble.

Dupixent, the blockbuster anti-inflammatory drug from Sanofi and Regeneron, has cleared a high-stakes Phase III study in chronic obstructive pulmonary disease, the companies announced Thursday morning.

If they hold up in a second, identical trial, the data pave the way for Dupixent to become the first biologic to treat patients whose COPD remains uncontrolled despite being on maximal standard-of-care inhaled therapy — the patient population studied in the pivotal program. The companies had spotlighted this as a key readout as they look to expand the Dupixent franchise and explore its full potential.

Novartis is calling off a UK-based trial for Leqvio in the primary prevention of cardiovascular events in patients with high cholesterol, the company confirmed on Wednesday.

The Swiss pharma giant made the decision after “careful evaluation,” a spokesperson told Endpoints News via email. The trial, dubbed ORION-17, was planned in partnership with England’s National Health Service (NHS) and was part of the company’s strategy to establish Leqvio as a standard of care in cardiovascular disease management.