#GSK2857916

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Top Pharma News of the Week

Top Pharma News of the Week

US FDA approves AstraZeneca’s Calquence (acalabrutinib) for adult patients with previously-treated mantle cell lymphoma

October 31, 2017

AstraZeneca and its haematology research and development centre of excellence, Acerta Pharma, have announced that the US Food and Drug Administration (FDA) has granted accelerated approval to Calquence (acalabrutinib). Calquence is a kinase inhibitor indicated…

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B-cell Maturation Antigen (BCMA) Targeted Therapies Market – Increasing Number of Multiple Myeloma is expected to the Boost Growth of the Market

Overview:

Multiple myeloma (MM) is a type of blood cancer. In multiple myeloma, cancerous plasma cells accumulate in the bone marrow and crowd out healthy blood cells. Plasma cells are an important part of the immune system, helping to fight a variety of infections and diseases. MM is a type of blood cancer and characterized by renal failure, low blood counts, hypercalcemia, monoclonal gammopathy, immune suppression, and anemia. Moreover, it remains an incurable disease. As reported by the American Cancer Society, in 2017, more than 30,280 new cases of multiple myeloma will be diagnosed in the United States and over 12,590 people will die from the disease. Furthermore, as reported by the National Center for Biotechnology Information (NCBI), MM represented 8.2% of all blood cancers in 2014 in Africa.

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B-cell maturation antigen (BCMA) has become an important therapeutic target in MM. The expression profiles displayed by Transmembrane Activator and CAML Interactor (TACI) and BAFF-receptor (BAFF-R) are comparatively lower than those of BCMA in people with MM. Moreover, these antigens are rarely detected in malignant plasma cells, thus BCMA is preferred as a standard alternative over other antigens. Therefore, BCMA-targeted therapies have gained traction for cancer treatment and is the choice of treatment for MM. BCMA is an important therapeutic target in MM with three modalities of treatment in development, such as bispecific T-cell engagers (BITEs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T-cell therapies (CAR T-cell therapies).

Drivers:

Increasing number of recurring cases of MM across the world is expected to augment growth of the global B-cell maturation Antigen (BCMA) targeted therapies market during the forecast period. Patients undergoing radiation therapy and chemotherapy are at higher risk of cancer recurrence because they develop resistance to these therapy. At this time, there is no cure for recurrent cancer and therefore BCMA targeted therapies provide successful therapeutic options for the treatment of recurrent MM.

Moreover, market players are focusing on developing and launching novel therapies (such as BITEs, ADCs, and CAR T-cell therapies), which in turn is drive to accelerate the global B-cell maturation Antigen (BCMA) targeted therapies market growth. For instance, GlaxoSmithKline Plc., in November 2017, received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for GSK2857916 monotherapy in patients with multiple myeloma who have failed at least three prior lines of therapy, including an anti-CD38 antibody and are refractory to a proteasome inhibitor and an immunomodulatory agent.

[pharmaphorumuk]

GSK files multiple myeloma drug with FDA after phase 2 success

GSK has filed for FDA approval of its potential first-in-class multiple myeloma drug belantamab mafodotin for relapsed/refractory multiple myeloma on the basis of a set of strong results from a phase 2 trial.

Also known as GSK2857916, belantamab mafodotin is an antibody-drug conjugate with the antibody component targeting the B-cell maturation antigen monoclonal antibody, linked to the cytotoxic agent auristatin F via a non-cleavable linker.

Latest results from the DREAMM-2 trial show an overall response rate (ORR) of 31% with a 2.5 mg/kg regimen and no new safety signals in heavily pre-treated patient populations who were refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory or intolerant to an anti-CD38 antibody.

The drug’s Breakthrough Therapy status with the FDA, reserved for medicines that could improve care standards in serious diseases, suggests that a faster six-month review period could be on the cards and a potential launch midway through 2020 if the review goes well.

Patients in the trial received a median of seven prior lines of treatment, were refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory and/or intolerant to an anti-CD38 antibody. The median duration of response has not been reached at six months of follow-up.

While there are a host of drugs already approved for multiple myeloma, patients can usually expect to live for around three years after diagnosis with the cancer of plasma cells and bone marrow, although some can live for up to a decade.

With these results from the open label study GSK hopes to become the first anti-BCMA agent available in the US.

Thirty of the 97 patients (31%) in the 2.5 mg/kg cohort achieved an overall response. Of these responders, 18 patients achieved a very good partial response or better, including three patients with stringent complete or complete responses. Overall survival in patients achieving a response was not reached in the six-month follow-up period.

The safety and tolerability profile was consistent with previously reported data on belantamab mafodotin. The three most commonly reported Grade 3 or 4 adverse events in the 2.5 mg/kg arm were keratopathy (27%), thrombocytopenia (20%) and anemia (20%). Keratopathy is characterised as changes in the corneal epithelium as seen on an eye examination which can manifest with or without symptoms.

Corneal events leading to treatment discontinuation affected 1% of patients in the 2.5 mg/kg cohort.

GSK is also testing belantamab mafodotin as a third-line monotherapy in relapsed/refractory multiple myeloma and in combination with standard and novel treatments in the first and second line setting.

Johnson & Johnson’s Janssen unit is another company trying to target BCMA – its CAR-T therapy JNJ-68284528 which works on the receptor was granted Breakthrough Therapy status in multiple myeloma by the FDA earlier this month.

AbbVie has also been trying to develop its Venclexta (venetoclax) in multiple myeloma but had to stop recruiting to the BELLINI trial after a safety scare earlier this year.

The latest news from Venclexta, revealed at the American Society of Hematology conference earlier this month, is that it seems to work safely in a group of myeloma patients who have a certain set of mutations.

The post GSK files multiple myeloma drug with FDA after phase 2 success appeared first on .

from https://pharmaphorum.com/news/gsk-files-multiple-myeloma-drug-with-fda-after-phase-2-success/

[nickyhants]

Listen to John Yates of GSK present "GSK2857916: First-in-class anti-BCMA ADC agent for treatment of multiple myeloma" at our 4th Biologics Symposium at The Babraham Institute on 1st October 2019. To see the list of speakers and to secure your place visit our website (link in bio). #Biologics #LabChat #myeloma #labwork #GSK #GlaxoSmithKline #bioassays #immunotherapy #LabLife #PhDLife #biotherapeutics #assays #Babraham #Cambridge #BiologicsSymposium #Promega #PromegaUK #laboratorywork #immunooncology #cancerresearch #oncologyresearch #assays #antibodydiscovery #antibodyinhibitors #humantissue #ADCagent #reagents #multiplemyeloma https://ift.tt/2V0GUMk

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R&D: GSK à la recherche de composés à des stades précoces

GlaxoSmithKline (GSK) souhaite acquérir les droits d'actifs à un stade précoce de développement et est prêt à nouer des partenariats avec d'autres entreprises, a déclaré mardi sa directrice générale, Emma Walmsley, lors d'une intervention à la 37ème conférence sur la santé organisée par la banque d'affaires JP Morgan à San Francisco.

Emma Walmsley a également indiqué que le groupe britannique pouvait conclure des accords de licence et qu'il continuerait à investir dans des projets précoces dans le VIH (où il est présent via la joint-venture ViiV Healthcare, dans laquelle il est majoritaire).

GSK nourrit par ailleurs de grands espoirs dans son composé GSK2857916, un anticorps conjugué visant BCMA actuellement en phase II dans le myélome multiple. Le groupe table sur un accès au marché courant 2020.

Le produit dispose depuis l'automne 2017 des statuts PRIME en Europe et de Breakthrough Therapy aux Etats-Unis pour une utilisation en monothérapie en 4e ligne, rappelle-t-on.

Plus largement, Emma Walmsley a souligné que son groupe avait doublé la taille de son pipeline en immuno-oncologie en quelques mois. Le renforcement dans le cancer repose notamment sur l'acquisition de la société américaine Tesaro, annoncée en décembre 2018 (cf dépêche du 03/12/2018 à 16:13).

[cancersfakianakis1]

Targeting BCMA Achieves Deep and Durable Responses in Multiple Myeloma [Research Watch]

Targeting BCMA with the antibody–drug conjugate GSK2857916 is well tolerated in a phase I trial.

https://ift.tt/2Ah2a6q

[medipaper]

via MediNews

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GSK therapy for multiple myeloma receives breakthrough therapy designation

GSK therapy for multiple myeloma receives breakthrough therapy designation

The Food and Drug Administration (FDA) has granted breakthrough therapy designation to GlaxoSmithKline (GSK) for its investigational B-cell mutation agent (BCMA) monoclonal antibody-drug conjugate, GSK2857916, for relapsed and refractory multiple myeloma.

Expand

This investigational therapy has also been granted PRIME designation from the European Medicines Agency (EMA) back in October for…

[pharmaphorumuk]

GSK scores major trial win with potential multiple myeloma blockbuster

GlaxoSmithKline may have scored a major cancer trial win after its belantamab mafodotin hit targets in the pivotal DREAMM-2 trial in relapsed multiple myeloma.

The company announced positive results for the trial in 196 patients with relapsed myeloma, who were refractory to an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody such as Janssen’s Darzalex.

R&D chief Hal Barron said that regulatory filings are due later this year for the drug which has come from nowhere to become a blockbuster contender, as GSK refocuses on oncology after selling off most of its cancer assets to Novartis a few years ago.

The two-arm study met its primary objective and demonstrated a clinically meaningful overall response rate with belantamab mafodotin in the patient population.

Safety and tolerability figures were consistent with that observed in DREAMM-1, the first time in human study of belantamab mafodotin.

GSK already announced findings of DREAMM-1 in March in patients with relapsed/refractory disease, confirming that 60% of patients receiving it achieved an overall response rate after an encouraging interim analysis almost two years ago.

Formerly known as GSK2857916, belantamab mafodotin is an immune-conjugate comprising a humanised anti-B cell maturation monoclonal antibody (BCMA) attached to a cytotoxin via a non-cleavable linker.

The drug linker technology is from Seattle Genetics, and the monoclonal antibody is producing using technology licensed from BioWa.

Belantamab mafodotin had been under the radar until the FDA granted it Breakthrough Therapy designation, and the suggestion is that it could be a more convenient alternative to CAR-T cell therapies targeting BCMA that are in the pipeline.

Celgene has invested in experimental CAR-Ts from bluebird bio and Juno targeting BCMA, and Novartis and Johnson & Johnson are also developing potential cell therapies that could be used in multiple myeloma.

But the experience with CAR-Ts that have made it to market is that they are expensive and cumbersome to administer.

An antibody-based therapy with similar capabilities would likely be popular with prescribers in health systems that are looking for cost-effective medicines.

If approved analysts think the drug could garner sales north of $1 billion a year, which would be most welcome as GSK looks to revive its fortunes.

Sales have been hit as generics have finally been approved for its ageing respiratory blockbuster Advair in the US, after years of delays.

Dr Hal Barron, chief scientific officer and president of R&D at GSK, said: “I am pleased with the results of the DREAMM-2 study and excited about what these data could mean for patients with multiple myeloma who have exhausted other lines of treatment.

“We are on track to file belantamab mafodotin later this year and continue to investigate how it could help even more patients with this disease.”

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from Pharmaphorum https://pharmaphorum.com/news/gsk-scores-major-trial-win-with-potential-multiple-myeloma-blockbuster/

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Janssen CAR-T is Priority Medicine in EU, and more

European regulators are to hasten development of Janssen’s CAR-T therapy for patients with multiple myeloma, after promising early-stage trial results. Janssen, the pharma arm of Johnson & Johnson, said the European Medicines Agency has granted a PRIME (PRIority MEdicines) designation for the investigational B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy, JNJ-4528.

Janssen has been developing the CAR-T previously known as LCAR-B38M with China’s Legend Biotech following a deal signed in December 2017.

JNJ-4528 is being investigated for patients with multiple myeloma who have received at least three prior treatments, including a proteasome inhibitor, an immunomodulatory drug, and Janssen’s anti-CD38 antibody Darzalex (daratumumab). These are seriously ill patients that have exhausted almost all other treatment options.

US biotech bluebird bio and partner Celgene are competitors and have two BCMA CAR-T therapies in early stage development for multiple myeloma, while Amgen’s AMG 420 has also emerged as a potential contender with some spectacular remission rates in a small trial announced last September.

But all these drugs are unproven and need more rigorous scientific data to convince regulators to approve them, although bluebird may file data for one of its BCMA CAR-Ts in the next year or so.

GlaxoSmithKline’s GSK2857916 is also considered a competitor. Although it is an antibody it also targets BCMA and has produced some strong data in multiple myeloma, prompting GSK’s chief scientific officer Hal Barron to pledge a rapid filing with regulators late last month.

The first CAR-T therapy accepted by the Chinese regulator for review, Legend has granted Janssen a worldwide licence to jointly develop and market JNJ-4528 in multiple myeloma in a deal where the US biotech paid $350 million up front.

Outside Greater China the companies are splitting costs and profit halfway, while Janssen and Legend have arranged a 30/70% cost-profit sharing agreement within the area.

PRIME offers more interaction and early dialogue to optimise development plans, with the possibility of a faster review for scientific advances targeting a high unmet medical need.

Radiopharmaceuticals

Radiopharmaceuticals are already well established in imaging technology for a range of diseases – but their use to deliver a lethal dose of radiation to cancer cells is also gaining increased attention.

Bayer’s Xofigo (radium 223) was a trailblazer in this field following FDA approval in 2013 – a calcium mimic, the drug selectively binds to bone metastases in prostate cancer to deliver a localised dose of radiation.

Novartis has placed its big bet in therapeutic radiopharmaceuticals with its $3.9 billion buy of Advanced Accelerator Applications and its Lutathera (lutetium Lu 177 dotatate), approved by the FDA early last year for tumours known as GEP-NETS (gastroenteropancreatic neuroendocrine tumours).

Now US-based Fusion Pharmaceuticals has raised $105 million in an oversubscribed second funding round to advance its work in the field. The company started off just two years ago with a $25 million launch round.

Led by Varian and new investor OrbiMed, additional investors participating in the round are Perceptive Advisors, Pivotal bioVenture Partners, and Rock Springs Capital.

They joined existing investors Healthcap, Adams Street Partners, Johnson & Johnson Innovation, TPG Biotech, Seroba Life Sciences, Genesys Capital, and FACIT.

Fusion, which is based in Hamilton, Ontario, Canada, and Boston, Massachusetts, will use the funding to broaden the scope of a clinical programme investigating alpha therapeutics.

These use antibodies attached to an alpha particle emitter to seek out tumours and deliver a dose of alpha radiation to the malignant tissue, while leaving healthy cells alone.

The lead drug in Fusion’s pipeline is [225Ac]-FPI-1434, which the company hopes to develop to target cancer cells across several tumour types.

Fusion’s drugs are based around a “linker” between the alpha emitter and the antibody, which promotes rapid excretion of isotopes that are not bound to cancer cells to limit off-target side effects.

Rubraca shows promise in pancreatic cancer

Clovis Oncology’s Rubraca has become the latest PARP drug to show potential in pancreatic cancer, as pharma companies seek new uses outside ovarian cancer where this class first gained a foothold.

US-based Clovis cited interim data from a phase 2 study, which trialled the drug in platinum-sensitive patients with advanced pancreatic cancer.

Clovis said that early data are encouraging and suggest that first-line maintenance therapy with Rubraca, following induction with platinum-based chemotherapy, provides disease control.

There were no new safety signals among patients with a pathogenic mutation in BRCA1, BRCA2, PALB2 – which are present in between 5-8% of patients with pancreatic cancer.

Pancreatic cancer is notoriously difficult to treat, not least because symptoms often become apparent after the disease is well established, making effective drugs all the more important.

Clovis cautioned that this is early data, but said it is looking to find a way forward with regulators to develop Rubraca (rucaparib) for pancreatic cancer following the success of AstraZeneca and Merck & Co’s rival Lynparza (olaparib).

In February AZ and Merck announced phase 3 results from the POLO trial showing Lynparza, the first PARP (poly (ADP-ribose) polymerase) drug on the market, significantly improved progression-free survival in patients with germline BRCA-mutated forms of the disease.

Clovis’ University of Pennsylvania-based study is an ongoing, single-arm phase 2 trial investigating monotherapy Rubraca (600 mg twice daily) in the first-line maintenance setting.

It will enrol 42 patients with advanced pancreatic cancer and a pathogenic germline or somatic BRCA1, BRCA2, or PALB2 mutation, whose cancer has not progressed following at least four months of platinum-based chemotherapy.

The primary endpoint of the trial is progression-free survival and responses are determined using standard RECIST v1.1 criteria.

At the interim analysis, the median progression-free survival (PFS) in 19 evaluable patients was 278 days or 9.1 months from the start of Rubraca therapy. At a median potential follow-up of 244 days, median overall survival (OS) had not been reached.

According to the authors, of the 19 patients evaluated at the last data cut-off, one patient had a complete response and six more patients had partial responses, including responses in patients with germline BRCA2 mutations (n=4), germline PALB2 mutations (n=2) and somatic BRCA2 mutation (n=1).

Eight of the 19 patients were on Rubraca for more than six months and two patients remained on treatment for more than a year (13 months and 15 months).

The disease control rate – a complete or partial response and stable disease, at eight weeks follow-up, was 89.5%.

Clovis also cited safety data, showing Rubraca was well tolerated without dose-limiting toxicities.

Side effects were all low-grade, most commonly nausea and distortion of the sense of taste, but there were no side effects above grade three.

BMS-Celgene oncology merger looks good to go

Bristol-Myers Squibb’s mega-merger with Celgene looks set to go ahead after activist hedge fund Starboard Value backed out of a campaign against the $74 billion deal.

The move came after a series of other developments that shore up the future of Celgene’s biggest selling blockbuster drug, Revlimid, which could generate sales in excess of $10 billion this year.

Late last week Starboard Value backed down from its campaign after two leading advisory firms backed the deal, advising shareholders to vote in its favour in a vote due later this month.

Institutional Shareholder Services (ISS) and Glass Lewis said on Friday that Bristol-Myers Squibb shareholders should vote in favour of the deal on April 12.

The hedge fund will continue to vote against the merger, which it has criticised because of concerns about the profitability of Celgene’s drugs after the merger goes ahead.

Starboard’s main concern is about Revlimid, which is due to go off patent in key markets in coming years, and whether the merged company will be able to get enough new drugs approved to make up for the shortfall in sales.

However, Starboard said it would stop its campaign against the deal in light of the ruling from the two advisers.

Starboard said in a statement: “Despite the substantial swell of support against the transaction, it is extremely difficult for shareholders to prevail without a supportive recommendation from ISS and Glass Lewis to vote against the transaction.”

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from Pharmaphorum https://pharmaphorum.com/views-analysis-oncology/janssen-car-t-is-priority-medicine-in-eu-and-more/

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EU regulators to fast-track Janssen’s multiple myeloma CAR-T

European regulators are to hasten development of Janssen’s CAR-T therapy for patients with multiple myeloma, after promising early-stage trial results.

Janssen, the pharma arm of Johnson & Johnson, said the European Medicines Agency has granted a PRIME (PRIority MEdicines) designation for the investigational B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy, JNJ-4528.

Janssen has been developing the CAR-T previously known as LCAR-B38M with China’s Legend Biotech following a deal signed in December 2017.

US biotech bluebird bio and partner Celgene are competitors and have two BCMA CAR-T therapies in early stage development for multiple myeloma, while Amgen’s AMG 420 has also emerged as a potential contender with some spectacular remission rates in a small trial announced last September.

But all these drugs are unproven and need more rigorous scientific data to convince regulators to approve them, although bluebird may file data for one of its BCMA CAR-Ts in the next year or so.

GlaxoSmithKline’s GSK2857916 is also considered a competitor. Although it is an antibody it also targets BCMA and has produced some strong data in multiple myeloma, prompting GSK’s chief scientific officer Hal Barron to pledge a rapid filing with regulators late last month.

The first CAR-T therapy accepted by the Chinese regulator for review, Legend has granted Janssen a worldwide licence to jointly develop and market JNJ-4528 in multiple myeloma in a deal where the US biotech paid $350 million up front.

Outside Greater China the companies are splitting costs and profit halfway, while Janssen and Legend have arranged a 30/70% cost-profit sharing agreement within the area.

PRIME offers more interaction and early dialogue to optimise development plans, with the possibility of a faster review, for scientific advances targeting a high unmet medical need.

The EMA made its decision based on results from the phase 1/2 LEGEND-2 study testing LCAR-B38M CAR-T cells, sponsored by Nanjing Legend Biotech.

It also considered results from the phase 1b/2 CARTITUDE-1 study testing JNJ-4528, sponsored by Janssen and conducted in partnership with Legend Biotech USA.

JNJ-4528 is being investigated for patients with multiple myeloma who have received at least three prior treatments, including a proteasome inhibitor, an immunomodulatory drug, and Janssen’s anti-CD38 antibody Darzalex (daratumumab).

Patients must have documented disease progression within 12 months of starting the most recent therapy, or are double refractory to a proteasome inhibitor and immunomodulatory drug.

These patients have few treatment options available and are often faced with poor outcomes.

Sjaak Bot, head of EMEA regulatory affairs at Janssen Biologics, said: “The PRIME designation of this novel BCMA CAR-T therapy highlights the value of regulatory innovation in the European Union.

“We hope to bring this important advance to patients as quickly as possible and this PRIME designation, the first for Janssen, marks an important milestone towards potential market approval.”

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from Pharmaphorum https://pharmaphorum.com/news/eu-regulators-to-fast-track-janssens-multiple-myeloma-car-t/

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GSK mulls filings for multiple myeloma drug

GlaxoSmithKline has announced more data making the case for its multiple myeloma antibody-drug conjugate GSK2857916, confirming that almost two thirds of patients responded to the drug after an extra year’s follow-up.

GSK will add more data to that announced by the company’s R&D guru, Dr Hal Barron, and plans to file the drug with regulators by the end of the year.

The positive news from GSK came after AbbVie and Roche announced they had stopped recruiting to studies of venetoclax in multiple myeloma, a potential contender in the multiple myeloma drug market following a safety scare in the phase 3 BELLINI trial.

The GSK trial is small, but the company is waiting on further data from the DREAMM-2 trial in multiple myeloma patients who have already been treated with an anti-CD38 antibody, Janssen’s Darzalex (daratumumab).

GSK announced the updated data from the DREAMM-1 study in patients with relapsed/refractory disease, confirming that 60% of patients receiving it achieved an overall response rate (ORR).

ORR was identical to that previously reported in an interim analysis first presented at the American Society of Haematology Congress in 2017, after more than a year of follow-up.

GSK said that the new figures not only showed potential efficacy but the durability and depth of response – the number of patients achieving a complete response increased to 15% over the additional one-year follow-up period.

Median progression-free survival was 12 months, an increase from the previously reported 7.9 months of progression-free survival (PFS), and the median duration of response in the final analysis was 14.3 months.

All patients whose data were reported in the interim analysis were included in the final analysis.

A total of 35 patients were enrolled in Part 2 of the DREAMM-1 study independent of their B cell maturation antigen (BCMA) expression levels.

Amongst those heavily pre-treated patients not previously treated with Darzalex, the ORR was 71% with a median PFS of 15.7 months.

In those patients who had previously been treated with daratumumab, the ORR was 38.5% with a median PFS of 7.9 months.

No new safety signals were identified during this treatment period. The most commonly reported adverse events were thrombocytopenia (63%), blurred vision (51%) and cough (40%), which were mostly mild or moderate (Grade 1 or 2).

The most commonly reported Grade 3 or 4 adverse events were thrombocytopenia (35%) and anaemia (17%) and were found to be manageable.

Hal Barron

Dr Hal Barron, chief scientific officer and president of R&D at GSK, said: “These data are very encouraging and I am excited by what they could mean for people living with multiple myeloma. We are aggressively advancing this potential new medicine and plan to have pivotal data to support its filing by the end of this year.”

Also known as GSK’916, the drug is also being developed for other multiple myeloma patients and other advanced haematologic malignancies expressing BCMA.

Planned studies include DREAMM-3 testing GSK’916 head-to-head against Celgene’s blockbuster Revlimid (pomalidomide) and low-dose dexamethasone, and the separate DREAMM-4 trial testing GSK’916 in combination with Merck & Co’s Keytruda (pembrolizumab) is already recruiting patients.

GSK2857916 is an antibody-drug conjugate comprising a humanised anti-B cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker.

The drug linker technology is licensed from Seattle Genetics and the monoclonal antibody is produced using technology licensed from BioWa, part of Japan’s Kyowa Kirin.

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from Pharmaphorum https://pharmaphorum.com/news/gsk-mulls-filings-for-multiple-myeloma-drug/

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GSK bolts-on immuno-oncology candidate with €3.7bn Merck deal

GlaxoSmithKline is making another big play in cancer, signing a wide-ranging deal with Merck KGaA for M7824, an immuno-oncology drug that made a splash at last year’s ESMO meeting.

The global alliance gets off the ground with a 300 million euro payment to Merck from GSK to secure co-development and co-marketing rights to the bifunctional fusion protein immunotherapy, an anti-PD-L1/TGF beta trap in clinical trials for solid tumours including non-small cell lung cancer (NSCLC).

The deal includes another €500 million tied to a lung cancer programme and €2.9 billion in additional development and commercial milestones that takes the totally tally to a hefty €3.7 billion (around $4.2bn).

The excitement at ESMO stemmed from phase I data showing a much higher response rate with M7824 (bintrafusp alfa) in patients with NSCLC than would be expected with first-generation PD-1/PD-L1 inhibitors such as Merck & Co/MSD’s Keytruda (pembrolizumab), which dominates the NSCLC market.

The result lent credence to the German drugmaker’s hypothesis that M7824’s dual antagonism of PD-L1 and TGF beta provides a double-whammy that could mean more patients respond to the cancer immunotherapy. At the moment, around a third of patients treated with the first generation of PD-1 inhibitors as a monotherapy don’t respond.

If M7824 can outperform Keytruda in this setting it could unlock a multibillion-dollar market in NSCLC alone, leaving aside its potential in other tumour types. Merck and GSK are planning an ambitious development programme, with at least eight trials of the drug on the go by the end of this year.

The data with M7824 has caught GSK’s eye as it continues a revamp of its pipeline and operations launched by CEO Emma Walmsley when she took over the helm of the company in 2017, with a big push into oncology spearheaded by new R&D chief Hal Barron.

“M7824 brings together two different biological functions in a single molecule and we have observed encouraging clinical results in treating certain cancer patients,” said Barron of the new alliance. “Despite recent medical advances, many patients with difficult-to-treat cancers don’t currently benefit from immuno-oncology therapies leaving them with limited treatment options.”

Cancer isn’t the only area of focus for the new GSK, but it is certainly an important one, and the Merck deal coming shortly after the company paid $5.1 billion to acquire Tesaro and its PARP inhibitor Zejula (niraparib) for ovarian cancer, a rival to AstraZeneca’s class-leading Lynparza (olaparib).

The Tesaro deal also brought in a PD-L1 inhibitor and other assets that Walmsley said had doubled GSK’s immuno-oncology pipeline, even before the Merck alliance.

GSK pretty much exited the cancer market commercially when it sold its marketed products to Novartis in 2015, but with big deals now done for the company’s consumer health and vaccines divisions—and a planned separation of consumer health from pharma—the company has refocused its attention on its pipeline.

That includes candidates like its in-house developed BCMA-directed antibody-drug conjugate GSK2857916 for multiple myeloma, which according to EvaluatePharma could be a blockbuster by 2024 – assuming it launches on schedule next year. That programme has already picked up a breakthrough designation from the FDA, and a speedy review may be needed as the anti-BCMA pipeline is getting fairly crowded.

Another key project is GSK3377794, a NY-ESO-1-targeted T cell therapy that GSK licensed from Adaptimmune and is in several clinical trials in cancers including sarcoma, myeloma, NSCLC, melanoma and ovarian cancer.

For Merck, it might have been expected that M7824 would have attracted the attention of Pfizer, already its partner for underperforming checkpoint inhibitor Bavencio (avelumab), and it is possible that GSK had to outbid its rival or other suitors to claim control of the asset.

According to Merck’s CEO Belén Garijo, “GSK clearly emerged as the ideal partner due to their strong commitment to oncology, and the complementary talent and capabilities they will bring to our alliance.”

The two companies will jointly conduct development and commercialisation of M7824, with all profits and costs from the collaboration being shared equally on a global basis.

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GlaxoSmithKline dévoile une "nouvelle approche" de R&D utilisant l'analyse génétique

GlaxoSmithKline (GSK) a dévoilé mercredi, à l'occasion de la publication de ses résultats du deuxième trimestre, une "nouvelle approche" de R&D visant à mettre l'accent sur le système immunitaire et s'appuyant sur l'analyse génétique.

Avec la performance (maîtrise des coûts et amélioration de la rentabilité) et la confiance (qualité des produits), l'innovation thérapeutique est l'un des trois piliers de la feuille de route pour 2020 présentée mi-2017 par la directrice générale, Emma Walmsley, à son arrivée (cf dépêche du 26/07/2017 à 16:54). 

Ce pilier a été précisé dans le communiqué des résultats du deuxième trimestre, qui évoque également un plan de restructuration visant à financer le développement des nouveaux produits (cf dépêche du 25/07/2018 à 17:45).

"Au coeur de cette nouvelle approche se trouve l'identification de nouveaux médicaments par la concentration sur les voies de modulation du système immunitaire, l'exploitation du grand nombre des données génétiques humaines aujourd'hui générées, l'analyse de ces données complexes grâce à l'apprentissage automatique (machine learning) et la création d'une culture de responsabilité où la prise de risque intelligente est récompensée", détaille le directeur scientifique de GSK, Hal Barron, ancien de Roche et Calico (groupe Alphabet, maison-mère de Google), arrivé en janvier.    

La R&D de GSK se concentrera sur "la biologie de base du système immunitaire" et sur les "cibles qui ont un haut degré de validation" par "la génétique humaine". Cette validation permettra de générer des médicaments avec une "haute probabilité de succès (deux fois plus importante qu'aujourd'hui)", justifie le laboratoire britannique.

Il indique que 60% de son pipeline de médicaments et de vaccins (soit 27 actifs sur 40 environ) en phase clinique est constitué de molécules immunomodulateurs, dont "plus de la moitié" ont le potentiel d'être les premiers représentants de leur classe.

Parmi ses actifs les plus prometteurs, le laboratoire mentionne le lancement d'ici 2020 de l'association fixe des deux anti-VIH dolutégravir (Tivicay*, Viiv Healthcare) et rilpivirine (Edurant*), ainsi que de la combinaison cabotégravir + Edurant*. Le groupe entend aussi lancer l'anticorps conjugué BMCA GSK2857916 dans le myélome multiple.

Plus loin dans son communiqué, il fait savoir qu'il a stoppé le développement du composé GSK3196165 dans l'arthrose. Des résultats de phase II dans la polyarthrite rhumatoïde (PR) seront présentés lors d'un prochain congrès.

Le groupe fait valoir que "l'accès aux bases de données pouvant être utilisées pour évaluer l'impact de la variation génétique sur la maladie offre des opportunités significatives pour améliorer le développement de médicaments". "Investir dans des plateformes technologiques avancées [...] pour soutenir l'interprétation des données génétiques sera une part importante pour permettre la nouvelle approche de R&D", indique-t-il.

Il entend aussi investir dans la "génomique fonctionnelle" en vue de "valider les cibles potentielles, les techniques d'application pour la modification génétique comme la technologie Crispr", ainsi que dans les capacités informatiques en vue d'"évaluer l'indication potentielle, la sélection, le séquençage et la gestion de la génération de preuves pour les nouveaux actifs".

"Cette nouvelle approche va demander d'investir et de changer la culture au sein de la R&D de GSK" par des partenariats, du recrutement de nouveaux talents et la formation de ses employés.

Partenariat avec 23andMe  

Dans un autre communiqué, GSK a annoncé un accord pour quatre ans (et une cinquième année en option) avec la société spécialisée dans l'analyse génétique 23andMe, dans laquelle il va investir 300 millions de dollars.

L'accord doit permettre de "transformer les données génétiques et phénotypiques en activités de R&D".

GSK aura un accès exclusif à la vaste base de données d'ADN de 23andMe, qui pourra l'aider le cas échéant à développer de nouveaux traitements. Sur les cinq millions de clients de 23andMe, 80% ont accepté que leurs données soient utilisées à des fins de recherche médicale, souligne GSK. Toutes les activités de collaboration seront cofinancées à parité.

23andMe, qui est basé à Mountain View (Californie) comme Google -dans laquelle la maison-mère de ce dernier, Alphabet, a aussi investi-, est surtout connu pour ses tests salivaires grand public qui permettent aux utilisateurs de connaître leurs origines. Il a aussi depuis trois ans une filiale de R&D pharmaceutique avec laquelle travaillera GSK.

Un premier projet portera sur un inhibiteur de LRRK2 dans la maladie de Parkinson, actuellement en phase préclinique.