British drug­mak­er As­traZeneca is al­ready run­ning be­hind ear­ly com­peti­tors in the hunt for a Covid-19 vac­cine with in­ter­im da­ta that have re­ceived less-than-stel­lar feed­back. With those da­ta in hand, In­dia has said “no thanks” to an ear­ly ap­proval for the shot, po­ten­tial­ly set­ting the stage for even more set­backs.

On Tues­day, In­di­an reg­u­la­tors re­fused to grant As­traZeneca’s ade­n­ovirus-based Covid-19 vac­cine an emer­gency use au­tho­riza­tion based on a dearth of ad­e­quate safe­ty and ef­fi­ca­cy da­ta, Reuters re­port­ed, cit­ing lo­cal broad­cast­er NDTV.

In­dia’s ear­ly no comes just hours af­ter As­traZeneca’s in­ter­im da­ta were pub­lished in The Lancet un­veil­ing ex­pand­ed safe­ty da­ta and fur­ther break­ing down the 70% av­er­age ef­fi­ca­cy fig­ure that has con­found­ed an­a­lysts and cast doubts on whether the vac­cine will ever com­pete with more ef­fec­tive com­peti­tors from Pfiz­er and Mod­er­na — and maybe oth­ers yet to read out.

In a note to clients Wednes­day break­ing down the da­ta, SVB Leerink an­a­lyst An­drew Berens was less than kind to the ear­ly read­out, de­spite one of the dos­ing reg­i­mens in three Phase III tri­als — a half-dose first shot fol­lowed by a full-dose primer — hit­ting 90% ef­fi­ca­cy.

“The pub­li­ca­tion high­lights a num­ber of vari­ances in the dos­ing reg­i­mens uti­lized in these tri­als that could make it dif­fi­cult for the reg­u­la­to­ry agen­cies to have con­fi­dence in the op­ti­mum dos­ing pro­to­col for full ap­proval with­out ad­di­tion­al stud­ies,” Berens wrote.

For one, the big vari­abil­i­ty be­tween the low-dose/high-dose com­bo and the high-dose/high-dose reg­i­men—which on­ly post­ed 62% ef­fi­ca­cy across three pooled tri­als did lit­tle to in­spire con­fi­dence. The more ef­fec­tive reg­i­men could be enough to spur reg­u­la­tors’ in­ter­est, but there are prob­lems with that da­ta as well, Berens said; sig­nif­i­cant­ly few­er pa­tients re­ceived that reg­i­men and those who did typ­i­cal­ly skewed younger.

Mene Pan­ga­los

Mean­while lo­cal tri­al pro­to­cols var­ied wide­ly, Berens not­ed, with pa­tients re­ceiv­ing boost­er shots at dif­fer­ent in­ter­vals across study sites. On a call with me­dia Tues­day, As­traZeneca’s ex­ec­u­tive VP of bio­phar­ma R&D Mene Pan­ga­los said that vari­abil­i­ty in boost­er tim­ing wasn’t nec­es­sar­i­ly a bad thing: With glob­al de­mand and lim­it­ed sup­plies, pa­tients could be forced to wait on a sec­ond shot in the fu­ture.

Mean­while, Berens al­so cast doubt on the shot’s man­u­fac­tur­ing, which ap­peared to show vari­able strengths across dif­fer­ent pro­duc­tion sites. As­traZeneca ar­gued those dif­fer­ences were with­in a com­fort­able range giv­en the ge­o­graph­i­cal­ly dis­parate sup­ply chain, but Berens begged to dif­fer.

“We be­lieve this could be a detri­ment when at­tempt­ing to gain reg­u­la­to­ry ap­proval as the man­u­fac­tur­ing process may not be uni­form and tighter re­lease spec­i­fi­ca­tions for vac­cines are gen­er­al­ly pre­ferred,” he wrote.

Man­u­fac­tur­ing had been a boon for As­traZeneca in com­par­i­son to its ear­ly mR­NA-based vac­cine com­peti­tors from Pfiz­er and Mod­er­na. For one, As­traZeneca’s shot can be stored and dis­trib­uted in­def­i­nite­ly at room tem­per­a­ture while Pfiz­er’s shot, in par­tic­u­lar, re­quires stren­u­ous cold-chain lo­gis­tics that could make it hard to dis­trib­ute in de­vel­op­ing coun­tries.

With those ques­tions in mind, In­dia’s big no is both an im­me­di­ate sur­prise — the coun­try and its vac­cine gi­ant, the Serum In­sti­tute of In­dia, have been churn­ing out mil­lions of dos­es of the shot for lo­cal and in­ter­na­tion­al use — but could be a sign of things to come as As­traZeneca faces rolling re­view in the EU, UK and else­where.

The drug­mak­er on Tues­day said it was still await­ing US da­ta and would with­hold an FDA fil­ing in the mean­time.

As­traZeneca can al­so lean on its rel­a­tive­ly clean safe­ty pro­file — one of the high­lights from its Lancet pub­li­ca­tion. Across four pooled stud­ies en­com­pass­ing 20,000 pa­tients, As­traZeneca’s vac­cine saw 79 se­vere events com­pared with 89 events in the con­trol arms. As­traZeneca re­port­ed three cas­es of trans­verse myelitis, which caus­es swelling in the spinal cord, two of which were deemed un­re­lat­ed to the vac­cine.

The third case, which caused As­traZeneca’s vac­cine to go on clin­i­cal hold ear­li­er this year, was de­ter­mined to be “pos­si­bly re­lat­ed” to the shot, Berens wrote. That black mark aside, the vac­cine re­sult­ed in no hos­pi­tal­iza­tions or deaths in the three tri­als pooled for ef­fi­ca­cy while there were 10 hos­pi­tal­iza­tions and one death in the con­trol arms.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

Over the past three years, Endpoints News has spotlighted 60 women who have blazed trails and supercharged R&D across the biopharma world. And judging from the response we’ve received, to both our special reports and live events, telling their stories — including any obstacles they may have had to overcome — has inspired our readers in many different ways.

But change takes time, and the fact remains that women are still underrepresented at the upper ranks of the drug-making world.

After making it clear that the US’ current monkeypox vaccine supply is insufficient, the FDA on Tuesday authorized a new route of administration that should increase the number of available doses by five-fold.

Regulators cleared Bavarian Nordic’s Jynneos vaccine for intradermal injection in adults older than 18. Unlike subcutaneous injection — the current method by which vaccine is delivered under the skin — an intradermal jab goes directly into the skin. It’s believed that this method requires less vaccine, since the dermis is rich in dendritic cells which specialize in taking up foreign antigens and presenting them to the immune system, according to Daniel Kuritzkes, chief of infectious diseases at Brigham and Women’s Hospital in Boston.

The FDA’s Center for Drug Evaluation and Research on Tuesday released a warning letter sent last week to Amazon CEO Andy Jassy in Seattle for selling mole removal products over-the-counter, or, as the FDA explains, “introducing, delivering, or causing the introduction or delivery into interstate commerce of products that are unapproved new drugs.”

“There are no over-the-counter (OTC) drugs that can be legally sold for mole or skin tag removal, and FDA has safety concerns about drugs marketed OTC directly to consumers for these uses,” the agency said in its Aug. 4 warning.

Federal officials said yesterday that shipments of Eli Lilly’s bebtelovimab — one of the final two remaining mAb treatments for Covid-19 — would halt later this month, setting up a commercial market where the government no longer pays for the doses and hospitals and other clinics will have to purchase supplies.

According to ASPR, the arm of HHS that ships Covid-19 drugs, states have ordered 627,536 bebtelovimab courses, and 383,515 courses have been administered as of July 31. The US has paid Lilly a total of about $1.27 billion for all of the courses so far, amounting to about $2,100 per course to start and then receiving a discounted $1,833 ASP for the later part of the deal. According to the Wall Street Journal, Lilly’s list price for bebtelovimab is $2,100 per dose.

Pfizer is launching its second-ever rebate program, this time for Panzyga, its treatment for a rare neurological disease of the peripheral nerves.

The program began last month, according to STAT which first reported the news, and offers a refund of out-of-pocket costs for patients who must discontinue their course before the fifth treatment for “clinical reasons.”

Panzyga was approved back in 2018 to treat primary immunodeficiency (PI) in patients two years and older and chronic immune thrombocytopenia (cITP) in adults. It has since picked up an indication in chronic inflammatory demyelinating polyneuropathy (CIDP), a condition that’s characterized by weakness of the arms or legs, tingling or numbness, and a loss of deep tendon reflexes, according to the NIH.