The FDA is to begin a fast review of Incyte’s Jakafi (ruxolitinib) for patients with chronic graft-versus-host disease (GVHD), which cannot be treated with steroids.
The US pharma, which has partnered with Novartis to develop this first-in-class JAK1/JAK2 inhibitor, said the FDA will review data from the phase 3 REACH 3 study comparing Jakafi to best available therapy in patients aged 12 years and older with steroid refractory GVHD.
Jakafi has been approved by the FDA in acute GVHD since 2019 and has been on the US market since 2011 for myelofibrosis and also picked up an indication in polycythemia vera in 2014.
GVHD is a life-threatening complication following stem cell transplant to treat multiple myeloma and certain types of leukaemia and lymphoma.
The grafted stem cells are supposed to attack these blood cancer cells but can also begin attacking a patient’s organs.
The acute form of the disease occurs within 100 days of transplant, while the chronic form occurs at least 100 days after transplant and both affect multiple organ systems, including the skin, gastrointestinal tract and liver.
REACH3 is a randomised, open-label, multicentre phase 3 study sponsored by Novartis and conducted in collaboration with and co-funded by Incyte, testing the safety and efficacy of Jakafi compared with best available therapy in patients with steroid-refractory chronic GVHD.
Primary endpoint is overall response rate (ORR) at week 24 – the first day of the seventh treatment cycle – defined as the percentage of participants demonstrating a complete or partial response.
Key secondary endpoints include failure-free survival (FFS) and change in the modified Lee Symptom Scale (mLSS) score at Week 24.
Other secondary endpoints include best overall response (BOR), duration of response (DoR), overall survival (OS), and safety.
Results published at the American Society of Hematology (ASH) late last year showed an ORR of 49.7% in those treated with Jakafi, compared with 25.6% in patients receiving best available treatment (BAT).
FFS was not reached in the Jakafi group compared with 5.7 months in the BAT patients, while 24% showed a greater symptom improvement in the Jakafi group compared with 11% in the BAT group.
No new safety signals were observed and adverse events were consistent with the known safety profile of Jakafi.
Jakafi is marketed by Incyte in the US and by Novartis as Jakavi (ruxolitinib) outside the US.
The sNDA submission is based on the P-III REACH3 study assessing ruxolitinib vs best available therapy in adult and pediatric patients ≥12yrs. with steroid-refractory chronic GVHD. The findings were recently presented at the 62nd ASH Annual Meeting & Exposition
The study showed greater ORR @24wks. i.e 1EPs (49.7% vs 25.6%); @24wks. mFFS (not reached vs 5.7 mos.); greater symptom improvement per mLSS (24.2% vs 1.0%); no new safety signals were observed while AEs were consistent
The PR shortens the review period from 10 to 6mos. The anticipated PDUFA date is Jun 22, 2021
Click here to read full press release/ article | Ref: Businesswire | Image: The Business Journals
The NDA is based on two P-III TRuE-AD 1 & 2 assessing ruxolitinib cream (0.75%/1.5%, bid) vs vehicle (non-medicated cream) in 600 patients aged ≥12yrs. in a ratio (2:2:1) diagnosed with AD for at least 2yrs. and who were candidates for topical therapy
Patients who completed an assessment @8wks. were offered participation in the 44wks. long-term safety treatment extension period with ruxolitinib cream (0.75%/1.5%, bid)
The company submitted PRV along with NDA to the FDA which shortens the review period by 4mos. The anticipated PFUFA date is Jun 21, 2021
Click here to read full press release/ article | Ref: BusinessWire | Image: BusinessWire
The biopharma industry saw numerous deal terminations in 2020. Clinical and regulatory results, change in control limitations, and strategic reprioritizations were among the most common reasons for deal termination.
Sanofi and Hanmi’s agreement in 2015 ranked first under which Hanmi regained WW rights to its protein/peptide discovery technology, lapscovery. The second position goes to the Merck KGaA termination of its development and commercialization deal with Pfizer
This article is based on the 2020 biopharma deals data provided by Chris Dokomajilar of DealForma. PharmaShots has compiled a list of the top 20 terminations of 2020 based on total deal value
Sanofi Terminated its 2015 Agreement with Hanmi
In Nov. 2015, Hanmi granted Sanofi exclusive, worldwide rights to its protein/peptide discovery technology, lapscovery to develop and commercialize a late-stage GLP1-RA agonist, efpeglenatide weekly insulin, and a fixed-dose weekly GLP-1-RA/insulin drug combination for the treatment of diabetes. Additionally, Hanmi had an exclusive option to co-commercialize the products in Korea and China. Hanmi received $434.7M up front and was eligible for up to $3.8B in development, regulatory, and sales-based milestones, plus double-digit royalties. In May 2020, Sanofi terminated the agreement and Hanmi regained worldwide rights.
Merck KGaA Terminated its Development and Commercialization Deal with Pfizer
Merck KGaA partnered with Pfizer to jointly develop & commercialize MSB0010718C for multiple types of cancer. The companies would develop the Ab as a single agent and in combination with Pfizer’s and Merck KGaA’s portfolio of approved and investigational oncology therapies. Both companies would collaborate on up to 20 immuno-oncology clinical development programs expected to commence in 2015, including up to 6 trials in P-II or P-III. Pfizer and Merck KGaA also partnered separately to co-promote Pfizer’s Xalkori in the US and other markets. Merck KGaA received $850M up front and was eligible to receive up to $2B in regulatory and sales milestones. Both companies would jointly fund all development and commercialization costs and split profits. On Mar. 19, 2019, Merck & Pfizer discontinued the P-III trial (JAVELIN Ovarian PARP 100) due to clinical trial results to develop avelumab in combination with CT followed by maintenance therapy of avelumab in combination with PARP inhibitor (talazoparib) for LA or metastatic ovarian cancer (Stage III or Stage IV). On Mar. 13, 2020, the companies terminated their P-III JAVELIN Head and Neck 100 trial of Bavencio (avelumab) with CRT for LA SCCHN as it failed to hit its 1Eps.
AbbVie (Allergan) Terminated its Development and Commercialization Deal with Assembly Biosciences
In Jan. 2017, Assembly Biosciences granted Allergan exclusive, worldwide rights to co-develop and commercialize ABI-M201 and ABI-M301 for the treatment of ulcerative colitis and Crohn’s disease, plus an additional two drugs for the treatment of Irritable Bowel Syndrome with Diarrhoea, with Constipation (IBS-C), or Mixed (IBS-M). Allergan and Assembly shared development costs until proof-of-concept studies. Assembly received $50M up front and was eligible for up to $2.77B in milestones, plus royalties. In May 2020, AbbVie acquired Allergan and on Jun. 18, 2020, AbbVie, terminated the agreement with Assembly Biosciences.
Eli Lilly Terminated its 2017 Agreement with CureVac
In Oct. 2017, CureVac granted Eli Lilly rights to develop and commercialize its 5 mRNA cancer vaccines using CureVac’s RNActive technology for up to 5 cancer vaccines that target neoantigens across multiple tumor types. Lilly was responsible for target identification, clinical development, and commercialization. CureVac was responsible for mRNA design, formulation, and manufacturing of clinical supplies. CureVac had the option to co-promote vaccines in Germany. CureVac received $50M up front, an equity investment of $51M (€45M), and CureVac would be eligible to receive more than $1.7B in development and sales milestones if all 5 vaccines are successfully developed, plus tiered royalties. In Jun. 2020, Eli Lilly terminated the agreement.
Voyager Terminated its Option and License Deal with AbbVie
In Feb. 2019, Voyager granted AbbVie options to license exclusive, worldwide rights to vectorized antibody-based gene therapies for Parkinson’s and other neurodegenerative diseases. Voyager would perform preclinical development to vectorize antibodies directed against alpha-synuclein designated by AbbVie. AbbVie would select one or more vectorized antibodies to advance into IND-enabling studies and clinical development. Voyager would be responsible for research, IND-enabling, and P-I clinical activities and costs. After completing P-I, AbbVie had an option to license the vectorized alpha-synuclein antibody program for further clinical development and global commercialization for Parkinson’s disease and other synucleinopathies. Voyager received $65M up front and was eligible for up to $245M in preclinical and P-I option payments, up to an additional $728M in development and regulatory milestones for each alpha-synuclein vectorized antibody compound, and up to $500M in total sales milestones, plus tiered royalties. On Aug. 3, 2020, Voyager Therapeutics terminated the agreement with AbbVie.
AstraZeneca Terminated its Development and Commercialization Deal with Allergan
In Oct. 2016, AstraZeneca’s global biologics research and development arm, MedImmune, granted Allergan exclusive, worldwide rights to develop and commercialize MEDI2070. The IL-23 monoclonal antibody was being developed for the treatment of Crohn’s disease and ulcerative colitis and was developed in partnership with Amgen Inc. under a 2012 deal. AstraZeneca received $250M up front and was eligible for up to $1.27B in milestones, plus royalties. AstraZeneca would share one-third of all payments and royalties with Amgen Inc. Amgen would also receive a single-digit inventory royalty on MEDI2070. On Jan. 27, 2020, AstraZeneca and Allergan mutually terminated the agreement, Allergan funded the ongoing study of brazikumab in CD and UC including CDx.
Eli Lilly Terminated its Research Partnership and Option to License Agreement with NextCure
In Nov. 2018, Lilly signed a research partnership with NextCure with an option to license immuno-oncology therapies using NextCure’s FIND-IO platform. Lilly had the exclusive option to license the antibodies resulting from the study. NextCure received $25M up front and Lilly invested $15M in NextCure. If Lilly exercised its option to license the drug, NextCure would be eligible to receive up to $1.4B in milestones, plus royalties. On Jan. 10, 2020, Eli Lilly terminated the agreement with NextCure effective Mar. 3, 2020.
Bridge Biotherapeutics and Boehringer Ingelheim Mutually Terminated their Development and Commercialization Deal
In Jul. 2019, Bridge granted Boehringer exclusive, worldwide rights to develop and commercialize BBT-877 for the treatment of fibrosing interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF). The Bridge received $50.48M up front and was eligible for up to $1.23B in milestones, plus royalties. On Nov. 9, 2020, Bridge Biotherapeutics and Boehringer mutually terminated the agreement.
Voyager Terminated its License Option Deal with AbbVie
In Nov. 2018, Voyager granted AbbVie an option to license the development and commercialization of its vectorized antibodies targeting tau by combining AbbVie’s monoclonal antibody expertise and Voyager’s gene therapy platform and expertise to generate AAV vectors for the treatment of neurodegenerative diseases, including Alzheimer’s disease. Both companies planned to identify 5 antibodies based on Voyager’s gene therapy platform and select 3 antibodies for development. AbbVie had an option to license up to 2 antibodies following the completion of P-I and would be fully responsible for development costs. Voyager received $69M up front, and was eligible for up to $155M in preclinical and P-I option payments, and was eligible for up to $895M in development and regulatory milestones, plus royalties. On Aug. 3, 2020, Voyager terminated the agreement with AbbVie.
Amgen Terminated its 2006 Research Partnership with Cytokinetics
In Dec. 2006, Cytokinetics signed a research partnership with Amgen to develop CK-1827452 for the treatment of heart failure. Amgen had an exclusive option to license the drug candidate worldwide excluding Japan before the completion of a P-IIa study. Cytokinetics was responsible for initial development. Upon exercising its option, Amgen was responsible for all further development costs. Also, the partners developed cardiac myosin as a backup compound. Cytokinetics received $75M up front, including $33M in its common stock at a premium of $6.9M. Upon option exercise, Cytokinetics received a $50M option exercise fee and was eligible for up to $600M in development, regulatory, and sales milestones, plus escalating royalties. Cytokinetics had the option to co-fund the P-III study in exchange for additional royalties. If Cytokinetics decided to co-fund the study, it could co-promote the drug in North America. In 2013, Amgen licensed Japan rights, and in 2016 Amgen sublicensed the rights for Europe and the Commonwealth of Independent States to Servier. On Nov. 23, 2020, Amgen terminated the agreement and Cytokinetics regained worldwide rights for omecamtiv mecarbil and backup compound AMG 594. The termination was effective May 20, 2021. The sublicense agreement between Amgen and Servier would remain effective post-termination.
Roivant Terminated its Development and Commercialization Deal with Poxel
In Feb. 2018, Poxel granted Roivant Sciences and its subsidiary Metavant rights to develop and commercialize its oral therapy, Imeglimin, for T2 Diabetes. Poxel received $35M up front and was eligible for up to $600M in milestones, plus royalties. Roivant invested $15M in Poxel’s common stock by purchasing 1,431,399 ordinary shares at €8.5 per share. Roivant was responsible for worldwide development and commercialization. Poxel planned to contribute $25M to the development and had an option to co-promote the product. In Nov. 2020, Metavant terminated the agreement with Poxel for the development of Imeglimin following a strategic analysis.
Alexion Terminated its Development and Commercialization Deal with Affibody
In Mar. 2019, Affibody granted Alexion rights to develop and commercialize ABY-039 for IgG-mediated autoimmune diseases. Affibody received $25M up front and was eligible for up to $625M in development and sales-based milestones, plus tiered low double-digit royalties. Additionally, Affibody had an option to co-promote the bivalent antibody-mimetic targeting the neonatal Fc receptor (FcRn) in the US. In Feb. 2020, Alexion terminated the agreement following unfavourable early-stage data.
Boehringer Ingelheim Terminated its Development and Commercialization Deal with Zealand
In Jun. 2011, Zealand granted Boehringer Ingelheim exclusive, worldwide rights to develop and commercialize glucagon/GLP-1 dual agonists, including ZP2929, for the treatment of type-2 diabetes and obesity. Zealand received $52.4M up front, including reimbursements cost and $5.6M in research funding, and was eligible for up to $532.2M in development and commercial milestones, plus double-digit royalties. In Mar. 2020, Boehringer Ingelheim terminated the agreement and Zealand regained worldwide rights.
BMS (Celgene) Terminated its Development and Commercialization Deal with Jounce
In Jul. 2019, Jounce granted Celgene exclusive, worldwide rights to develop and commercialize JTX-8064 targeting the LILRB2 receptor on macrophages. Jounce received $50M up front and was eligible for up to $480M in milestones, plus royalties. In Jun. 2020, Bristol Myers Squibb terminated the agreement.
Cytokinetics Terminated its Development and Commercialization Deal with Astellas
In Jun. 2013, Cytokinetics granted Astellas exclusive, worldwide rights to co-develop and commercialize CK-2127107 for skeletal muscle weakness. Cytokinetics had the option to co-promote products in the US and Canada. Cytokinetics received $16M up front, $24M in R&D reimbursement, and was eligible for over $250M in development and sales milestones for collaboration products, including up to $112M for CK-2127107 and up to $200M in sales milestones, plus undisclosed royalties. On Dec. 22, 2014, Cytokinetics restated the agreement and granted Astellas exclusive, worldwide rights to co-develop & commercialize CK-2127107 and other products for SMA and other neuromuscular indications. Cytokinetics was responsible for P-II in patients with SMA and other neuromuscular diseases. Both companies would co-develop and co-commercialize CK-2127107 and other skeletal troponin activators in neuromuscular indications. Cytokinetics had the option to co-fund certain development costs, co-promote & conduct commercial activities for CK-2127107 in non-neuromuscular and neuromuscular indications in the US, Canada, and EU. On Jul. 27, 2016, Cytokinetics extended the agreement and granted Astellas additional rights to develop and commercialize tirasemtiv and CK-2127107 for ALS. Cytokinetics received a $100M option exercise fees and was eligible for additional milestones, plus royalties based on sales of tirasemtiv in Astellas’ countries. Also, Astellas was eligible for royalties based on Cytokinetics’ sales of tirasemtiv in its territory. On Apr. 23, 2020, the companies mutually terminated the agreement, Astellas contributed one-third of the development cost, or ~$12M, in an exchange of royalties in the US, Canada, and the EU for 10 years or reduced royalties until 2034. Also, Astellas returned all inventory and IP related to FRSA compounds and agreed not to engage in any research and development activities on FSRA compounds for 4 years.
Calithera Terminated its Development and Commercialization Deal with Incyte
In Jan. 2017, Calithera granted Incyte worldwide rights to develop and commercialize its arginase inhibitor, CB-1158, for the treatment of hematology and oncology indications. Incyte would fund 70% of the development cost while Calithera would fund 30%. Incyte and Calithera would share profits and losses, with Incyte at 60% and Calithera at 40%, based on U.S. sales. Incyte and Calithera planned to co-detail the drug in the U.S. and Calithera was eligible for up to $483M, including upfront and milestones, plus royalties ex-U.S. In Sep. 2020, Calithera terminated the agreement and regained worldwide rights.
Idorsia Terminated its Option and License Deal with Santhera for Vamorolon
In Nov. 2018, Idorsia granted Santhera an option to sublicense the development and commercialization of vamorolone for the treatment of DMD worldwide, excluding Japan and South Korea. Idorsia received 1M new registered shares of Santhera and an upfront cash payment of $20M. Idorsia became the largest shareholder in Santhera with a 13.3% equity position. The option was exercisable upon receipt of data from the P-IIb VISION-DMD study (VBP15-004). If exercised, Idorsia would receive a one-time payment of $30M and was eligible for regulatory & commercial milestones of up to $80M for the DMD indication and four one-time sales milestone payments of up to $130M in total. Idorsia was also eligible for regulatory milestone payments of up to $205M for three additional indications. On Sep. 2, 2020, Santhera exercised its option to license vamorolone for all indications including DMD, and revised the terms of the agreement. Vamorolone was originally developed by ReveraGen, and Actelion had the option rights. In Jun. 2017, Actelion spun off Idorsia as a separate entity along with vamorolone rights before its merger with Johnson & Johnson. According to the revised terms of the agreement, Idorsia received 366,667 shares in Santhera’s common stock and CHF10M in the form of convertible notes, up to 65% was converted in the form of Santhera common stock and transfer the control rights to its original developer ReveraGen BioPharma. Santhera had replaced Idorsia as party to the ReveraGen agreement.
AMAG Terminated its Development and Commercialization Deal with Palatin Technologies
In Jan. 2017, Palatin Technologies granted AMAG Pharmaceuticals rights to develop and commercialize Rekynda (bremelanotide) for the treatment of female sexual disorders in North America. Palatin received $60M up front, up to $380M in milestones, and $25M in reimbursement payments, plus royalties. In Jul. 2020, AMAG terminated the agreement and Palatin Technologies regained the rights plus $16.3M in termination fees.
Gilead Terminated its Development and Commercialization Deal with Precision BioSciences
In Sep. 2018, Precision granted Gilead rights to develop and commercialize therapies for Hepatitis B Virus targeting HBV cccDNA and integrated HBV DNA present in human hepatocytes using Precision’s ARCUS platform. Precision would focus on the development, formulation, and preclinical studies. Gilead was responsible for clinical studies and commercialization. Precision received research funding and was eligible for up to $445M in milestone payments and royalties. In Sep. 2020, Gilead terminated its agreement with Precision BioSciences.
ReveraGen Terminated its Option and License Deal with Actelion (Idorsia after the spin-off from Actelion)
In Nov. 2016, Actelion signed a research partnership with ReveraGen BioPharma with an option to license vamorolone for the treatment of DMD and other indications. Actelion would co-develop the compound for the next 28 months and would contribute $1M annually. ReveraGen received $10M up front, up to $165M in dev. and reg. milestones for DMD, and up to $190M for an additional three indications, plus tiered double-digit royalties. On Jun. 16, 2017, Actelion was acquired by Johnson & Johnson. Actelion spun off Idorsia as a new company. In 2018, Idorsia maintained the option rights for vamorolone and restructured the agreement. It agreed to contribute the research for an additional year (until mid-2020). ReveraGen initially received $15M to maintain the agreement, a $20M option fee, and would be eligible for up to $75M in milestones for the DMD indication, and three additional sales milestones of up to $120M. Royalties and milestone payments for other indications remain unchanged. In Nov. 2018, Idorsia granted Santhera an option to sublicense the development and commercialization of vamorolone for DMD worldwide, excluding Japan and South Korea. On Sep. 2, 2020, Santhera exercised its option to license vamorolone for all indications including DMD with the control rights transferred to ReveraGen BioPharma.
Incyte has filed its PD-1 inhibitor retifanlimab with the FDA, seeking approval to treat a form of anal cancer associated with human papillomavirus (HPV) and HIV infections.
The application covers the use of the intravenous PD-1 inhibitor for adults with advanced squamous cell carcinoma of the anal canal (SCAC) who have progressed on, or who are intolerant of, platinum-based chemotherapy, and an FDA decision is due by 25 July after a priority, six-month review.
If approved, retifanlimab (formerly INCMGA0012) would be the first PD-1/PD-L1 checkpoint inhibitor to be approved for SCAC, providing Incyte with a niche indication to grow the drug without competition.
That will be important, as retifanlimab is in line to be the seventh or eighth drug in the class to reach the market, coming after a roll call of big pharma oncology giants. It may get the nod before GlaxoSmithKline’s dostarlimab, also under review at the FDA for endometrial cancer.
Incyte’s drug is following in the footsteps of Merck & Co’s Keytruda (pembrolizumab), Bristol-Myers Squibb’s Opdivo (nivolumab), Roche’s Tecentriq (atezolizumab), AstraZeneca’s Imfinzi (durvalumab), Pfizer/Merck KgAA’s Bavencio (avelumab) and Sanofi’s Libtayo (cemiplimab), which collectively have dozens of approved uses.
Cases of SCAC have been on the rise in recent decades, but it is still relatively uncommon, accounting for about 4% of all anorectal tumours, according to a 2020 review paper.
In Europe, rates range from around 1 to 3 cases per 100,000 people, while in the US there were about 8,200 new cases of SCAC recorded in 2017. The FDA has granted orphan drug status to retifanlimab as that makes it a rare disease.
While survival rates for SCAC have increased thanks to refinements to first-line chemotherapy, patients with SCAC that has spread around the body have a poor chance of living beyond five years.
At the moment, there are no FDA-approved treatments for patients who have progressed after first-line chemo for this “historically neglected, yet important, tumour,” according to Icyte’s head of immuno-oncology Lance Leopold.
“Despite SCAC being a rare disease, its incidence is increasing and its impact is profound,” he added.
Incyte’s marketing application is based on the phase 2 POD1UM-202 trial reported at last year’s ESMO cancer congress, which found an objective response rate of 14% for retifanlimab, regardless of the tumour’s PD-L1 expression, whether it had spread to the liver, or the patient’s age or HIV status.
SCAC may be free of competition for Incyte’s drug, but the company’s development plan includes other indications that will put it in contention with the checkpoint inhibitor heavyweights.
It is in trials alongside chemotherapy in previously-untreated non-small cell lung cancer (NSCLC) – dominated at the moment by Keytruda – and SCAC, and as a monotherapy for microsatellite instability (MSI) high endometrial cancer and Merkel cell carcinoma.
Retifanlimab was originally developed by MacroGenics and licensed to Incyte in 2017 for $150 million upfront and up to $750 million in development and commercial milestones.
MacroGenics said in November it had claimed $25 million so far in milestone payments triggered by clinical and regulatory activities including the start of POD1UM-303, a phase 3 trial in SCAC.
Analysts don’t expect big sales from retifanlimab on its own – maybe in the ballpark of $500 million – but there could be upsides if the drug proves its value in combination with other therapies.
Those include a mid-stage study with MacroGenics’ margetuximab in HER2-positive gastric cancer that the partners think could lead to regulatory filings if the results are positive.
The EMA’s CHMP has adopted a positive opinion of pemigatinib for the treatment of adults with unresectable locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status, after at least one line of ST
The CHMP opinion is based on P-II FIGHT-202 and patients enrolled into one of three cohorts – cohort a (FGFR2 fusions or rearrangements), cohort b (other FGF/FGFR genetic alterations) or cohort c (no FGF/FGFR genetic alterations)
Pemigatinib will be the 1st targeted therapy indicated in the EU if approved for this indication
Click here to read full press release/ article | Ref: Businesswire | Image: BioSpace
The BLA submission is based on P-II POD1UM-202 trial involves assessing of retifanlimab (500 mg, q4w) in 94 patients with locally advanced or metastatic SCAC who have progressed on or are intolerant of standard platinum-based CT
The study demonstrates 14% ORR for retifanlimab monotherapy as determined by ICR using RECIST v1.1 and mDOR of 9.5mos
Retifanlimab has received FDA’s ODD for the treatment of anal cancer along with PR which shortens the review period by 4mos vs Standard Review. The PDUFA target action date is Jul 25, 2020
Click here to read full press release/ article | Ref: Businesswire | Image: Technical.ly
The companies collaborated to evaluate ruxolitinib in combination with CK0804 in patients with MF and plan to initiate a P-Ib study. Incyte will fund the study while operationalized by Cellenkos
Cellenkos to receive $20M as licensing fee, ~$294.5M as development, regulatory and commercialization milestones along with royalties on sales of therapies, if approved. Incyte has an exclusive option to acquire sole rights to develop and commercialize CK0804 in benign and malignant hematology indications
Following the exercising the global license option, Incyte to lead all activities and costs associated with research, development, and commercialization of the program
Click here to read full press release/ article | Ref: Businessiwre | Image: Businesswire
Novartis/Incyte’s Jakafi (ruxolitinib) looks unlikely to be added to the list of therapies that can be used against COVID-19, after it failed to cut complications or death in a phase 3 trial.
Data from the phase 3 RUXCOVID study showed that there was no significant reduction in the proportion of COVID-19 patients on ruxolitinib plus standard therapy experiencing severe complications, compared to standard care alone.
Severe complications included death, respiratory failure requiring mechanical ventilation or admission to intensive care.
RUXCOVID is a 29-day placebo-controlled trial testing ruxolitinib in 432 patients aged 12 years or over in patients hospitalised for COVID-19 and not intubated or receiving intensive care before randomisation.
Results were measured against a composite primary endpoint of patients who died, developed respiratory failure requiring mechanical ventilation, or required admission to ICU by day 29.
But the proportion of people meeting this endpoint was almost identical in the two groups – 12% for those treated with ruxolitinib and 11.8% for those treated with placebo plus standard care.
Patients were randomised 2:1 to receive ruxolitinib twice daily or oral-matching placebo for 14 days, with standard therapy decided according to the investigator’s clinical judgement.
Ruxolitinib is already FDA approved under the brand name Jakafi to treat the bone marrow diseases myelofibrosis, polycythemia vera and graft-versus-host disease.
Trials of the drug in other indications are not affected by the outcome, Novartis said.
The drug is an oral inhibitor of JAK 1 and JAK 2 tyrosine kinases and the rationale behind the trial was to investigate whether the down regulation of the immune system conferred by the medicine would reduce the inflammation caused by COVID-19.
Originally developed by Incyte, Novartis licensed in the drug for development and marketing outside the US.
The RUXCOVID trial is sponsored by Novartis outside of the US and by Incyte inside the US.
Many drugs are being trialled against COVID-19, with the cheap steroid dexamethasone producing some of the most promising trial results.
Although Gilead’s Veklury (remdesivir), an antiviral originally intended to treat Ebola, is approved in the US to treat COVID-19 the World Health Organization has recommended against using it because of differing interpretations of trial results.
The EUA is based on ACCT-2 study assessing baricitinib (4mg, qd for 14 days or until hospital discharge) in combination with remdesivir vs PBO with remdesivir in hospitalized patients with/ out oxygen requirements
Result: Median time to recovery from 8-7days (12.5% improvement), patients who progressed to ventilation (23% vs 28%), patients who died @day29 (4.7% vs 7.1%) with a relative reduction of 35%; better clinical status @day15
This marks the second Lilly therapy to be granted a EUA, in addition to neutralizing Ab EUA for high-risk non-hospitalized patients, increasing the number of treatment options for COVID-19 patients at different stages of the disease
Click here to read full press release/ article | Ref: Eli Lilly | Image: CNBC
Immunology is an important branch of science which deals with the study of the immune system. The immune system is a highly regulated and balanced system and when the balance is disturbed, the disease can result. A lot of this work has importance in the development of new therapies and treatments that can handle or heal the condition by modifying the way the immune system is working or, in the case of vaccines, instructing the immune system and enhancing the immune reaction to specific pathogens. In the top 20 ledgers, AbbVie again ensured the top position with total revenue of $19.57B with its blockbuster drug, Humira (adalimumab) from its immunological segment. Our team at PharmaShots has compiled a list of the top 20 immunology companies based on their 2019 immunology revenue
Immunology Segment Revenue: $0.01B
Founded Year: 1979
Market Cap: ~$0.49B
Total Employees: ~178
Headquarter: New Jersey, United States
Stock Exchange: NASDAQ
AntaresPharma is an American pharmaceutical company focus on developing and commercializing therapies for rheumatology, urology, endocrinology, and neurology. Antares has reported a total sale of $0.01B from its immunology segment in 2019
Immunology Segment Revenue: $0.24B
Founded Year: 2008
Market Cap: ~$15.70B
Total Employees: ~1,200
Headquarter: Dublin, Ireland
Stock Exchange: NASDAQ
Horizon Therapeutics is an Ireland based biopharmaceutical company focused on developing and commercializing therapies for the treatment of gout, rheumatoid arthritis, and rare diseases. Horizon has generated the sale of $0.24B from its four approved immunology products including Tepezza, Rayos, Duexis and Vimovo. Horizon’s Tepezza was selected for “2020 R&D World R&D 100 Award”
Immunology Segment Revenue: $0.49B
Founded Year: 1993
Market Cap: ~$2.57B
Total Employees: ~5,047
Headquarter: Shenyang, China
Stock Exchange: HKD
3SBio is a fully integrated Chinese biotechnology company with market-leading biopharmaceutical franchises in oncology, auto-immune diseases, nephrology, metabolic diseases, and dermatology. There are three approved drugs in its immunology portfolio including Yisaipu, Tpiao and Xenopax. 3SBio’s Tpiao used to treat chemotherapy-induced thrombopenia (approved in 2005) and immune thrombocytopenia has generated global sales of $0.33B in 2019.
Immunology Segment Revenue: $0.73B
Founded Year: 1978
Market Cap: ~$42.57B
Total Employees: ~7,400
Headquarter: Massachusetts, United States
Stock Exchange: NASDAQ
Biogen is a global biopharma company focused on neurology, hematologic, and autoimmune diseases. Biogen has a total of six products in its immunology segment with four approved drugs including Tysabri, IMRALDI, FLIXABI, BENEPALI. Biogen’s lead drug Tysabri recorded a revenue of $1.89B. Biogen revealed the positive result of BIIB059 in the Phase 2 LILAC study for cutaneous lupus erythematosus and systemic lupus erythematosus.
Immunology Segment Revenue: $0.81B
Founded Year: 2000
Market Cap: ~$88.14
Total Employees: ~99,000
Headquarter: Brentford, United Kingdom
Stock Exchange: LON
GlaxoSmithKline (GSK) is a global healthcare company serving the world with drugs, vaccines & consumer healthcare products. With only approved products, Benlysta, GSK has generated a revenue of $0.81B in 2019. In Jul 2019, GSK initiated the phase 3 study of otilimab for rheumatoid arthritis. In Sep’19, EMA granted a positive CHMP opinion for intravenous Benlysta in children with lupus and was approved in Oct 2019.
Immunology Segment Revenue: $1.11B
Founded Year: 2007
Market Cap: ~$34.6B
Total Employees: ~7,228
Headquarter: Osaka, Japan
Stock Exchange: TYO
Mitsubishi Tanabe is a Japanese pharma company focused on autoimmune diseases, diabetes and kidney diseases, neurological disorders, and vaccines. Mitsubishi has reported a total sale of $1.11B from its immunology segment in 2019.
Immunology Segment Revenue: $1.24B
Founded Year: 1891
Market Cap: ~$197.46B
Total Employees: ~71,000
Headquarter: New Jersey, United States
Stock Exchange: NYSE
Merck & Co. is a global health care company delivering innovative health care products with its Prescription medicines, Oncology drugs, Vaccines, Biologic therapies, and Animal Health care products. Merck has recorded the sale of $1.24B in 2019 from its five approved drugs in its immunology portfolio including Simponi, Remicade, Renflexis, Brenzys, Hadlima. Simponi and Remicade was co-commercialized by Merck and Johnson & Johnson and Simponi recorded the revenue of $0.83B in 2019.
Immunology Segment Revenue: $1.68B
Founded Year: 1991
Market Cap: ~$19.38B
Total Employees: ~1,300
Headquarter: Delaware, United States
Stock Exchange: NASDAQ
Incyte Corp is a global biopharmaceutical firm focused on developing therapies in two categories Oncology and Inflammation & Autoimmune. Incyte has generated a revenue of $1.68B from its immunological segment. In Jan’19, Incyte reports results of Itacitinib in GRAVITAS-301 P-III study for patients with treatment-naive acute graft-versus-host disease.
Immunology Segment Revenue: $1.79B
Founded Year: 2005
Market Cap: ~ $26.49B
Total Employees: ~15,883
Headquarter: Tokyo, Japan
Stock Exchange: TYO
Astellas Pharma is a Japanese multinational pharmaceutical company focused on the therapeutic fields of urology, immunology including transplantation and infectious diseases, oncology, neuroscience and DM complications, and metabolic diseases. Astellas has four drugs in its immunology portfolio including two approved drugs Smyraf And Prograf and has recorded the sale of $1.79B in 2019. In Jul’19, Astellas Pharma launched Smyraf 50 mg and 100 mg tablets for rheumatoid arthritis.
Immunology Segment Revenue: $1.79B
Founded Year: 1901
Market Cap: ~$135.16B
Total Employees: ~33,625
Headquarter: Indiana, United States
Stock Exchange: NYSE
Eli Lilly and Company is a global pharmaceutical firm focused on delivering therapies in two divisions Human Pharmaceutical Products and Animal Health products. The pharmaceutical portfolio offers products for Cardiovascular, Endocrinology, Immunology, Neuroscience, and Oncology. Eli Lilly has two approved drugs including Taltz and Olumiant. Lilly’s Taltz, an approved drug for plaque psoriasis or psoriatic arthritis has generated a revenue of $1.6B in 2019. In Apr’19, Eli Lilly signs research and licensing agreement with avidity biosciences to develop therapies in immunology.
Immunology Segment Revenue: $1.92B
Founded Year: 1928
Market Cap: ~$20.49
Total Employees: ~7,600
Headquarter: Brussels, Belgium
Stock Exchange: EBR
UCB is a global biopharmaceutical company focused on neurology, inflammatory, gastrointestinal and autoimmune disorders. UCB has recorded the sale of $1.92B in 2019 from its immunology segment with its only approved drug, Cimzia indicated for psoriatic arthritis (PsA). In Jul’19, Cimzia was approved by China’s NMPA.
Immunology Segment Revenue: $2.53B
Founded Year: 1973
Market Cap: ~$122.35B
Total Employees: ~100,000
Headquarter: Paris, France
Stock Exchange: EPA
Sanofi is a global healthcare leader in vaccines providing healthcare solutions in 170+ countries around the world. Sanofi is ranked third in the global market and first in EU and Latin America. Sanofi has four drugs in its immunology portfolio including one approved drug Kevzara, developed in partnership with Regeneron. In Dec’19, Sanofi presented the positive result from its pivoted phase 3 study of sutimlimab for cold agglutinin disease. Additionally, Sanofi restructured its agreement with Regeneron to obtain worldwide rights for Kevzara.
Immunology Segment Revenue: $2.97B
Founded Year: 1887
Market Cap: ~$135.30B
Total Employees: ~30,000
Headquarter: New York, United States
Stock Exchange: NYSE
Bristol-Myers Squibb is an American pharmaceutical company focused on Oncology, Cardiovascular, Immuno-Science, and Fibrosis. BMS has two approved drugs Orencia and Nulojix. BMS’ Orencia is a protein indicated to treat adult rheumatoid arthritis, juvenile idiopathic arthritis, and adult psoriatic arthritis has generated the highest revenue of $2.97B in 2019. The acquisition of Celgene in 2019, has boosted up BMS’ Immunology pipeline.
Immunology Segment Revenue: $3.66B
Founded Year: 1925
Market Cap: ~$52.60B
Total Employees: ~49,578
Headquarter: Osaka, Japan
Stock Exchange: TYO
Takeda is a global biopharma company focused on Oncology, Gastroenterology (GI), Neuroscience, Immunology, and Rare Diseases. With three approved drugs including Immunoglobulin, Albumin, and Entyvio, Takeda has generated a $3.66B sale in 2019. In Apr’19, EMA accepted the application for a subcutaneous formulation of Entyvio in Crohn’s disease, and in Oct 2019, Takeda acquired CNP-101 from COUR Pharmaceuticals. In Feb’20, Takeda acquired PvP Biologics to strengthen its immunology pipeline. Additionally, Takeda got approval for Entyvio from China’s NMPA for Crohn’s disease in Mar 2020.
Immunology Segment Revenue: $4.22B
Founded Year: 1996
Market Cap: ~$205.93B
Total Employees: ~109,000
Headquarter: Basel, Switzerland
Stock Exchange: SIX Swiss Exchange, NYSE
Novartis is a multinational group of companies specializing in research, development, manufacturing, and marketing with a broad range of healthcare solutions including generic and ophthalmic therapies. The company is focused on Immunology, Hepatology, Dermatology, Oncology, Neurology, and Ophthalmology. Novartis has the uppermost number of immunology drugs with eight approved products including ACZ885/Ilaris, AIN457/Cosentyx, Myfortic (Renal transplant), Neoral, Simulect, and Zortress. Novartis’ Cosentyx (secukinumab) used to treat Psoriasis, ankylosing spondylitis and psoriatic arthritis have generated global sales of $3.55B in 2019. In Apr’19 Novartis acquired IFM Tre to enhance its immunologic portfolio with its NLRP3 inhibitors for $1.5B.
Immunology Segment Revenue: $4.73B
Founded Year: 1849
Market Cap: ~$206.05B
Total Employees: ~83,000
Headquarter: New York, United States
Stock Exchange: NYSE
Pfizer is a research-based, global biopharmaceutical company having a vast portfolio including Oncology, Medicines, vaccines, and other health care products for the prevention & treatment of untreated diseases. With 3 approved drugs including Xeljanz, Enbrel (outside the US and Canada), and Inflectra (Biosimilar), Pfizer has generated $4.73B sale from its immunology portfolio indicated for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, Behcet’s disease, and ulcerative colitis. Pfizer’s Xeljanz has generated revenue of $2.24B in 2019. In Jan’2019, CytoReason signed a research partnership with Pfizer to develop drugs using CytoReason’s cell-centered models of the immune system.
Immunology Segment Revenue: $5.39B
Founded Year: 1980
Market Cap: ~$134.11B
Total Employees: ~23,400
Headquarter: California, United States
Stock Exchange: NASDAQ
Amgen is one of the leading biotechnology company developing novel therapies focused on cardiology, oncology, neurology, nephrology, and inflammatory diseases. Amgen has generated a total sale of $5.39B in 2019 with its drugs Otezla, Avsola, Enbrel, Nplate, and Prolia. Amgen’s Otezla used to treat certain types of psoriasis and psoriatic arthritis has generated sales of $1.6B.
Immunology Segment Revenue: $8.79B
Founded Year: 1896
Market Cap: ~$281.59B
Total Employees: ~98,000
Headquarter: Basel, Switzerland
Stock Exchange: SWX
Roche Holding AG is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. The immunology department focus on rheumatoid arthritis (RA), systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, and giant cell arteritis including severe persistent allergic asthma (AA), chronic idiopathic urticaria (CIU), and idiopathic pulmonary fibrosis (IPF) with 3 approved drugs including Actemra, CellCept and Mabthera and has generated the sale of $8.97B in 2019. In Dec’2019, Roche signed an exclusive global option and license agreement with Rheos Medicines to develop and commercialize therapies for immune metabolism.
Immunology Segment Revenue: $13.95B
Founded Year: 1887
Market Cap: ~$378.94B
Total Employees: ~132,100
Headquarter: New Jersey, United States
Stock Exchange: NYSE
Johnson & Johnson (J&J) is an American multinational healthcare company focused on the development and commercialization of pharmaceutical, medical device, and consumer packaged products. The pharmaceutical portfolio offers products for Cardiovascular, Endocrinology, Immunology, Neuroscience, and Oncology. J&J has generated $13.95B from its Immunology portfolio with 5 approved products including Remicade, Simponi, Stelara, Tremfya, Simponi Aria. Remicade was jointly marketed by J&J and Merck and has generated a revenue of $4.38B in 2019. In Nov 2019, J&J’s Tremfya meets the primary endpoint in the phase 3 study for Psoriatic Arthritis. Additionally, J&J submit two applications with the USFDA for Polyarticular Juvenile Idiopathic Arthritis and Juvenile Psoriatic Arthritis. FDA approved Tremfya for Psoriatic Arthritis and Simponi Aria for polyarticular juvenile idiopathic arthritis and active psoriatic arthritis for patients 2 years of age and older in Jul 2020.
Immunology Segment Revenue: $19.57B
Founded Year: 2012
Market Cap: ~$146.29B
Total Employees: ~30,000
Headquarter: Illinois, United States
Stock Exchange: NYSE
AbbVie is a global, research and development-based biopharmaceutical company focused on developing innovative advanced therapies. The company is focused on developing products in immunology, oncology, virology, and neuroscience, dermatology. AbbVie has generated the sale of $19.57B in 2019 from its immunological segment with 3 approved drugs including RINVOQ, SKYRIZI, HUMIRA. AbbVie’s blockbuster drug HUMIRA recorded a revenue of $19.16B. In Apr’2019, AbbVie received EMA approval of SKYRIZI for Plaque Psoriasis. Its RA drug RINVOQ received FDA approval in Aug 2019 and EMA approval in Dec 2019. Additionally, RINVOQ achieved positive results in primary and key secondary endpoints for Psoriatic Arthritis and subsequently submitted the regulatory applications with the FDA and EMA.
The companies shared the additional efficacy and safety data of the ACTT-2 study demonstrating baricitinib + remdesivir reduced time to recovery and improved clinical outcomes for patients with COVID-19 infection compared with remdesivir as monothx
The biggest benefits were observed in patients requiring supplemental oxygen (grade 5 on the eight-point ordinal scale) and those who required high-flow oxygen/non-invasive ventilation (grade 6) at baseline
Additionally, Eli Lilly is in talks with the US FDA for EUA of baricitinib (JAK1/JAK2 inhibitor licensed to Lilly from Incyte) to treat hospitalized patients with COVID-19
Click here to read full press release/ article | Ref: Eli Lilly | Image: Strateos Blog
The FDA approved Monjuvi for second-line diffuse large B-cell lymphoma. Though the drug has the same antigen target as approved CAR-T cell therapies, it is designed for patients unable to tolerate such intensive treatments.
Incyte and Morphosys’ Monjuvi antibody therapy has been approved for certain patients with lymphoma, as the companies hope to provide a more convenient alternative to expensive and cumbersome CAR-T therapy.
At the beginning of the year Incyte paid $750m to Morphosys for the CD-19 targeting antibody, which has been approved in combination with BMS’ Revlimid (lenalidomide) for adults with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified.
The indication also covers DLBCL arising from low grade lymphoma and patients not eligible for autologous stem cell transplant.
Monjuvi (tafasitamab) targets the CD-19, a protein on the surface of B-cells that is also targeted by Amgen’s bispecific antibody Blincyto (blinatumomab) for acute lymphoblastic leukaemia (ALL), as well as two CAR-T therapies – Novartis’ Kymriah (tisagenlecleucel) and Gilead’s Yescarta (axicabtagene ciloleucel) – that are already approved for DLBCL and other B-cell cancers.
Under the agreement with Morphosys the companies will co-market the drugs in the US, while Incyte has exclusive rights outside the US.
The deal with Morphosys could see Incyte pay up to $1.1 billion should certain targets be achieved.
Xencor, which developed the drug before licensing it to Morphosys in 2010, will receive a $25 million milestone payment and a royalty on worldwide net sales.
There was no word from the companies on pricing, but an antibody drug is likely to be less expensive than the rival CAR-T therapies also approved in DLBCL, at least in the short term.
Novartis and Gilead have priced their CAR-Ts at $373,000 for adult DLBCL, covering the cost of a single shot of the cell therapy.
Monjuvi will be taken in a longer cycle and antibody therapies already on the market cost several thousand dollars per month.
Still it’s unlikely that the price will exceed the headline cost of the CAR-Ts and they will also be more convenient.
CAR-Ts are made by harvesting a patient’s own cells and modifying them to fight cancer, a lengthy process that might not appeal to all patients.
There are also dangerous side-effects with CAR-Ts, where doctors often have to manage “cytokine storms” where the immune system goes into overdrive and begins to attack a patient’s own body.
The FDA approval of Monjuvi was based on data from the MorphoSys-sponsored phase 2 L-MIND study, an open label, multicentre, single arm trial of Monjuvi in combination with lenalidomide as a treatment for adult patients with relapsed or refractory DLBCL.
Results from the study showed an overall response rate of 55%, including a complete response rate of 37% and a partial response rate of 18%.
Warnings and precautions for Monjuvi included infusion-related reactions, serious or severe myelosuppression (including neutropenia (50%), thrombocytopenia (18%), and anemia (7%)), infections (73%) and embryo-foetal toxicity. Neutropenia led to treatment discontinuation in 3.7% of patients.
This accelerated approval may depend on further confirmatory data from larger trials.
Novartis has axed development of its mid-stage eczema drug ZPL389, taking a $485 million hit in the process.
Buried deep in the Swiss company’s Q2 results statement, the company said it had discontinued development of the oral H4 receptor antagonist.
Novartis added ZPL389, also known as adriforant, to its pipeline with a buyout of UK biotech Ziarco in late 2016.
At that time Sanofi was cruising towards an important FDA approval for its Dupixent (dupilumab) injection for the skin disease also known as atopic dermatitis.
Noting the blockbuster potential for drugs that treat the underlying cause of the inflammatory disease driven by the immune system, several other big pharma companies tried to get in on the act.
But three years after buying Ziarco for an undisclosed sum, Novartis said the phase 2 drug had been scrapped.
Novartis had been eyeing a potential filing with regulators in 2024 or later.
It’s perhaps not a surprise as the drug had missed an endpoint related to itch in a phase 2a study shortly before Novartis bought out Ziarco.
The drug had outperformed placebo at reducing eczema symptoms, which had been enough to convince Novartis that the project was worth investing in.
It’s the latest disappointment for Novartis and its bid to take on Dupixent, which has become one of Sanofi’s most important drugs with sales of 776 million euros ($880 million) in Q1 after approval in eczema and asthma.
Novartis paid $110 million for global rights for Galapagos and MorphoSys anti-IL-17C antibody MOR106 in 2018 – but the biotech axed development in October last year after an analysis midway through a phase 2 trial showed it was likely to fail.
Spain’s Almirall is another company hoping to take on Sanofi – it has licensed in lebrikizumab from Dermira.
Almirall is hoping that the IL-13 inhibitor class drug will be a strong competitor for Dupixent, which has a different mechanism of action focused on IL-4.
Incyte is also planning a US filing of its atopic dermatitis cream containing ruxolitinib before the end of this year.
The topical formulation of the JAK1/2 inhibitor hit targets in a pair of phase 3 trials that produced readouts earlier this year.