Michael Weiss, TG Therapeutics CEO

FDA rais­es con­cerns over TG Ther­a­peu­tic­s' sur­vival da­ta, plans to con­vene ODAC

TG Ther­a­peu­tics took a hit Tues­day morn­ing af­ter an­nounc­ing the FDA will con­vene an ad­comm ahead of the biotech’s up­com­ing PDU­FA date for a blood can­cer com­bo ther­a­py, throw­ing a po­ten­tial de­ci­sion in­to lim­bo.

Though the ex­act date has not been de­ter­mined, reg­u­la­tors are look­ing to hold a meet­ing of the On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee some­time in March or April, TG said in a re­lease. Giv­en that tim­ing, the biotech says it’s now un­like­ly the FDA will reach an ap­proval de­ci­sion by the March 25 dead­line.

“We look for­ward to the ODAC meet­ing as we be­lieve it will pro­vide us an op­por­tu­ni­ty to high­light the im­por­tant role U2 can play in the treat­ment of CLL,” CEO Michael Weiss said in a state­ment.

In the wake of the news, TG shares $TGTX cratered by near­ly 45% as the mar­ket opened Tues­day morn­ing.

The pro­gram in ques­tion is a com­bi­na­tion of ubli­tux­imab and um­bral­is­ib, which the biotech has re­ferred to as U2 (no re­la­tion to the Bono-led band). TG has been re­search­ing the ther­a­py to treat adults with chron­ic lym­pho­cyt­ic leukemia and small lym­pho­cyt­ic lym­phoma.

Ac­cord­ing to TG, the FDA is call­ing ODAC to­geth­er over ques­tions about the pro­gram’s over­all sur­vival ben­e­fits, some­thing that was not an­a­lyzed in the in­ter­im analy­sis, Weiss said in an in­vestor call Tues­day. OS had been in­clud­ed as a sec­ondary mea­sure, but was in­stead pow­ered to mea­sure pro­gres­sion-free sur­vival.

TG pro­vid­ed sur­vival in­fo to reg­u­la­tors as part of the BLA and sN­DA re­view, but Weiss not­ed it was not in­clud­ed orig­i­nal­ly. The CEO said TG and the FDA had agreed be­fore the study that the sur­vival da­ta would have been too im­ma­ture and “too small to be in­for­ma­tive” had the com­pa­ny at­tempt­ed to mea­sure OS.

The da­ta TG even­tu­al­ly pro­vid­ed in­clud­ed an ear­ly analy­sis show­ing no sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence in sur­vival be­tween the treat­ment arms, Weiss said. He high­light­ed that the haz­ard ra­tio of 1.23 ap­peared to show an im­bal­ance in fa­vor of the con­trol arm, though when ex­clud­ing deaths re­lat­ed to Covid-19, the HR fell to 1.04 — again with no sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence.

Weiss al­so at­tempt­ed to ease in­vestor con­cerns over the hear­ing, ex­plain­ing that there is “prece­dent” for the ap­proval of drugs that seem­ing­ly fa­vor sur­vival con­trol arms. He point­ed to Ab­b­Vie and Roche’s Ven­clex­ta as one ex­am­ple, not­ing the drug had “no ODAC and OS was clear­ly in fa­vor of the GC arm at the time of ap­proval,” in re­sponse to an an­a­lyst ques­tion.

Time will tell whether ODAC heeds the FDA’s con­cerns, but the news marks an­oth­er bump in TG’s quest to get the U2 com­bo past the fin­ish line — tim­ing that re­mains up in the air. In Sep­tem­ber 2018, the biotech was sup­posed to read out ORR da­ta for the ther­a­py but the safe­ty mon­i­tor­ing board said at the time the da­ta weren’t ma­ture enough.

TG brought in­vestors back to the ta­ble in May 2020, how­ev­er, read­ing out pos­i­tive topline Phase III re­sults that showed it hit the PFS thresh­old in an in­ter­im analy­sis. In the full dataset re­vealed at ASH in De­cem­ber 2020, TG showed off stel­lar p-val­ues in PFS and ORR (p<0.0001 and p<0.001, re­spec­tive­ly) while say­ing um­bral­is­ib as a monother­a­py al­so hit a 49.3% over­all re­sponse rate.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Who are the women blaz­ing trails in bio­phar­ma R&D? Nom­i­nate them for End­points' 2022 spe­cial re­port

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.

Up­dat­ed: Amid mas­sive re­struc­tur­ing, Bio­gen looks to re­duce phys­i­cal pres­ence in Boston

Biogen is putting a sizable chunk of office and research space in Kendall Square and Weston, MA up for sublease, marking another big change as the biotech grapples with the aftershock of a disastrous and controversial rollout for its Alzheimer’s drug.

The subbleases are “part of Biogen’s overall implementation of the ‘Future of Work,’ which is allowing us to optimize our footprint and reduce the amount of space we occupy, taking into consideration new elements such as the hybrid work model,” Biogen spokesperson Ashleigh Koss wrote in a statement to Endpoints News, adding that the company has had subleases across several buildings for years.

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Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

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Robert Califf, FDA commissioner (Tom Williams/CQ Roll Call via AP Images)

Hop­ing to ex­pand mon­key­pox vac­cine sup­ply, US paves the way for new route of ad­min­is­tra­tion

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.

Andy Jassy, Amazon CEO (Isaac Brekken/AP Images for NFL, File)

Up­dat­ed: FDA slaps Ama­zon with a warn­ing let­ter for sell­ing OTC mole re­moval prod­ucts

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.

Pfiz­er launch­es re­bate pro­gram for rare dis­ease pa­tients who have to stop tak­ing Panzy­ga

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.

Horizon's back-to-school campaign for children with cystinosis includes an all about me poster as part of a care package box.

Hori­zon read­ies kids and fam­i­lies for back to school with week­long ac­tiv­i­ties around rare dis­ease cysti­nosis

Going back to school is usually a bumpy readjustment from summer freedom for all kids, but especially for kids with chronic health conditions. Horizon Therapeutics is hoping to help smooth the way for some who have the rare disease cystinosis. Cystinosis is a genetic disease that causes the amino acid cystine to build up in different tissues and organs.

The “Gear Up” for school campaign is running all week with different online and at-home events and activities for families and children with cystinosis. Each family who signed up receives a care package mailed to their home including an activity coloring book “Michael’s Show-and-Tell.” The book tells Michael’s story about living with cystinosis while offering kids matching, coloring and finding object games along with information.

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Alessandro Maselli, Catalent CEO

Catal­ent ac­quires North Car­oli­na CD­MO for $475M, boost­ing oral solids work

As Catalent has been expanding its reach in the US this year, as well as recently completing a C-suite shuffle, the company announced last night that it has acquired the CDMO Metrics Contract Services for $475 million from Mayne Pharma Group.

The acquisition will increase Catalent’s capabilities in oral solid formulation development, manufacturing and packaging as well as expand its capacity to handle more highly potent compounds.

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