August 11, 2022

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Fiercepharma: 2021 Top Ten ADC Drug Competitors

Fiercepharma: 2021 Top Ten ADC Drug Competitors



 

Fiercepharma: 2021 Top Ten ADC Drug Competitors.

Recently, Fiercepharma ranked the top ten ADC drug competitors according to the global major pharmaceutical companies for ADC drug development in 2021.

 

Fiercepharma: 2021 Top Ten ADC Drug Competitors

 


0 1 Seagen

  • Number of ADCs under development: 8
  • Expects sales: 2021 was 10 billion dollars, 2022 year 13 billion dollars
  • Expected milestones: In October 2021, tisotumab vedotin will apply for PDUFA as a treatment for second-line advanced cervical cancer; and the key data for recurrent cervical cancer of tisotumabvedotin in 2021 and the key data of ladiratuzumab vedotin in triple-negative breast cancer in 2022.

In July 2021, the FDA issued to Seagen and its development partner Astellas the approval of Paddev for third-line metastatic or locally advanced bladder cancer, which was approved earlier than expected, and also for patients who are not eligible for cisplatin chemotherapy Provide second-line use. Analysts estimate that Padcev’s use only in bladder cancer should eventually push the drug to surpass the blockbuster.

Padcev and Seagen’s other FDA-approved ADC drug Adcetris are both key players in the company’s booming ADC pipeline.

Padcev is testing with Merck’s immuno-oncology giant Keytruda in bladder cancer and is also being tested in advanced solid tumors as a stand-alone treatment.

At the same time, Adcetris is conducting a number of clinical trials for blood cancer and solid tumors. Analysts estimate that the sales of these two listed ADCs will reach $1 billion this year and will rise to $1.3 billion next year.

Seagen has six other ADCs under development, including tisotumab vedotin, which may soon be approved by the FDA for cervical cancer.

The newest member of its product line includes diffatamabvedotin, a HER2-targeted ADC license obtained from RemeGen in China, with a transaction value of up to $2.6 billion.

Seagen already has HER2 targeted drugs in its product portfolio Tukysa, but the RemeGen deal makes it a potential competitor to two high-selling ADCs, AstraZeneca and DaiichiSankyo’s Enhertu and Roche’s Kadcyla.

 

 


0 2. Daiichi Sankyo

  • Number of ADCs under development: 7
  • Estimated sales:2021 fiscal year sales of 550 million U.S. dollars
  • Expected milestones: This year, Enhertu’s key data for the head-to-head trial of Roche Kadcyla in second-line HER2-positive breast cancer, and data from the second-line HER2 low-expressing breast cancer trial in 2022; FDA may approve Enhertu for second-line HER2 mutant non-small cells in 2022 Lung cancer.

Daiichi Sankyo caused a sensation in the biopharmaceutical industry in 2019, when AstraZeneca prepaid a huge amount of US$1.35 billion and pledged to provide a milestone amount of up to US$5.55 billion to obtain a license for trastuzumab deruxtecan.

 

Analysts predict that the drug will bring in sales of $5.7 billion in 2030, and bet that it will disrupt the Roche-led HER2 market.

From April to June, Enhertu’s global sales were 13 billion yen (approximately 120 million U.S. dollars). For the fiscal year ending in March next year, the Japanese company’s sales are expected to reach 61 billion yen (about 550 million US dollars).

 

Daiichi’s long-term ADC pipeline includes U3-1402 (patritumab deruxtecan), a HER3-targeted ADC that has begun key testing in EGFR-mutant NSCLC, and a phase 1 that combines ADC with AZ’s EGFR small molecule inhibitor Tagrisso test.

 

In addition, Daiichi has four other ADCs under development. The targets are B7-H3 , GRP20 , CDH6 and TA-MUC1 .

 

 


0 3. ADC Therapeutics

  • Number of ADCs under development: 6
  • Estimated sales: USD 23.1 million in 2021 and USD 79.1 million in 2022
  • Expected milestones: recently launched several trials of Zynlonta combination therapy for B-cell carcinoma; updated data also includes the launch of another ADC camidanlumab tesirine in Hodgkin’s lymphoma and ADCT-901 in solid tumors.

In April, ADC Therapeutics changed from a research and development institution to a mature commercial biopharmaceutical company.

Its first product, Zynlonta, was approved for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Zynlonta is a CD19-targeted ADC that was approved based on a phase 2 trial, with an overall response rate of 48.3% and a complete response rate of 24%.

The drug generated $3.8 million in sales in the first two months of its launch, which is a respectable performance considering the competition with other CD19 targeted therapies.

Analysts predict that the company’s sales this year will reach 23.1 million U.S. dollars, and next year it will bring 79.1 million U.S. dollars in sales.

 

Its other ADC camidanlumabtesirine is still in key trials, which is a CD25 targeted drug for the treatment of Hodgkin’s lymphoma.

In August, the company announced that in the Phase 2 trial, the drug produced a 66.3% response rate.

 

ADC Therapeutics’ long-term product line includes ADCs targeting tumor antigens AXL, KAAG1 and DLK1.

 

 


0 4. Roche

  • Number of ADCs under development: 2
  • Estimated sales: 2.26 billion Swiss francs (US$2.46 billion) in 2021 and 2.77 billion Swiss francs (US$3.02 billion) in 2022
  • Expected milestone: Data from the Phase 3 study of Polivy in first-line diffuse large B- cell lymphoma .

Roche may not have developed its own ADC platform, but by cooperating with other leaders in the field, it became the first company to have an FDA- approved product on the market . Now it has two ADC products.

 

Roche’s first ADC , Kadcyla , received the green light for HER2 metastatic breast cancer in 2013 , and had previously been treated with Roche’s own Herceptin and chemotherapy.

Its second ADC, Polivy , was approved by the FDA in 2019 for the treatment of diffuse large B- cell lymphoma ( DLBCL ) together with bendamustine and Roche’s Rituxan .

 

Kadcyla is developed using Immunogen’s ADC technology, which couples Herceptin (trastuzumab) with the microtubule inhibitor DM1 through the SMCC linker.

For Polivy, Roche used Seagen’s technology to couple the MMAE cytotoxic payload with the CD79b-targeting antibody through the mc-vc-PAB linker.

 

Supplementary indications are driving the growth of Kadcyla. In the first half of 2021, Kadcyla’s global sales were 959 million Swiss francs (1.05 billion US dollars), a year-on-year increase of 19%.

Analysts predict that Kadcyla’s sales will be relatively stable in the next few years.

The drug’s annual sales may reach a peak of US$2.6 billion from the expected US$2.3 billion in 2021, and will begin to decline in 2026.

 

While trying to promote the growth of Kadcyla, Roche is also working hard for Po livy’s heavy expansion.

As of September, Welford’s 2021 sales forecast for Roche’s two ADCs was 2.26 billion Swiss francs (US$2.46 billion), of which 233 million Swiss francs (US$254 million) came from Polivy.

 

 


0 5. Gilead Sciences

  • Number of ADCs under development: 1
  • Estimated sales: Trodelvy will be 362 million U.S. dollars in 2021 and 788 million U.S. dollars in 2022.
  • Expected milestones:Announcement of Trodelvy’s Phase 3 TROPiCS-02 data in HR-positive, HER2-negative metastatic breast cancer.

 

Gilead Sciences joined the ADC competition by acquiring Immunomedics for US$21 billion in 2020 .

The transaction is almost entirely concentrated on Trodelvy, and analysts predict that on a risk-adjusted basis, by 2030, Trodelvy’s sales may reach $4.5 billion.

 

Trodelvy the DNA topoisomerase inhibitor SN-38 as an effective load transfer to the expression of toxicity TROP-2 tumor cells.

Compared with other ADC platforms that usually use enzymes to cleave the linker , Trodelvy ‘s CL2A linker will decompose as the chemical environment changes.

 

Breast cancer is Trodelvy’s main battlefield, but TNBC market competition between ADCs is brewing.

Daiichi Sankyo and AstraZeneca are collaborating to develop their own TROP-2 ADC, datopotamab deruxtecan (DS1062). According to data from Evercore ISI, the payload DXd used by Daiichi is about 10 times more toxic than SN-38.

But one potential advantage of Trodelvy over datopotamab is that Daiichi’s ADC is associated with serious side effects of interstitial lung disease (ILD).

Six severe cases of ILD have been reported in the FDA’s adverse event reporting system and clinical trials of drugs.

 

In addition, another competitor is about to emerge: Merck has signed a contract to co-develop Seagen’s LIV-1 ADC drug candidate ladiratuzumab vedotin, which was originally developed for TNBC.

In the phase 1 trial of the drug, it caused a response in 25% of patients who had previously received a median of 3 treatment.

 

Gilead is also trying to expand to Trodelvy HR-positive, HER2-negative turn metastatic breast cancer. If the drug is successful, the potential peak global sales will reach $2.2 billion .

 

 


0 6. GSK

  • Number of ADCs under development: 1
  • Estimated sales: USD 155 million in 2021 and USD 304 million in 2022.
  • Expected milestones:The clinical trial results of its approved low-dose ADC Blenrep combined with a gamma secretase inhibitor to treat multiple myeloma will be announced; and trial data comparing the drug with standard care will be available within 18 months.

 

When GlaxoSmithKline received FDA approval for its ADC Blenrep in August 2020 , it was both a milestone and a disappointing milestone.

The drug was approved for patients with multiple myeloma who had failed four previous treatments. It was the first drug to target BCMA , but in Blenrep clinical trials, nearly 75% of patients had eye problems, some of which were severe To cause loss of vision. Result: There is a terrible ” black box ” warning on the drug label .

 

When Blenrep when approved, analysts predict that 2021 had sales of 2.87 billion pounds ( 3.77 billion dollars).

Now, it is estimated that this product will bring about 155 million U.S. dollars in revenue this year and 304 million U.S. dollars in revenue next year .

 

GSK has also conducted several Blenrep joint studies in multiple myeloma .

They include a Phase 3 study in combination with Velcade in second-line treatment , and a Phase 1 trial of cocktail therapy of Blenrep , Velcade, and Revlimid as first-line treatment .

 

 


0 7. Mersana Therapeutics

  • Number of ADCs under development: 4
  • Estimated sales: /
  • Expected milestones: It is expected that the phase 1 data of upifitamab rilsodotin (UpRi), the main drug candidate for ovarian cancer, will be updated later this year. Phase 1 data of UpRi and XMT-1592 in non-small cell lung cancer are expected to be released around the fourth quarter and the end of 2021, respectively. Phase 1 data of XMT-1660 and XMT-2056 are expected to start in early 2022.

 

Mersana Therapeutics has two ADC drugs to treat ovarian cancer and non-small cell lung cancer. The main drug candidate upifitamab rilsodotin and second-line project XMT-1592 is targeted NaPi2b , NaPi2b widely expressed in both cancer.

 

For UpRi , Mersana uses a platform called Dolaflexin . Unlike most other ADCs where toxic drugs are directly coupled to antibodies , Dolafelxin attaches drug molecules to a proprietary biodegradable polymer scaffold and then couples them to the antibody.

This increases the number of drug molecules that can be carried by each ADC , and Mersana hopes this will result in better efficacy.

 

In contrast, XMT-1592 is designed with the Dolasynthen platform, which uses a synthetic scaffold to more accurately control the amount of drug labeled on the antibody, so that the drug can be delivered to cancer cells more consistently.

 

UpRi shows some effects in ovarian cancer. In 1 the month of 1 update data dose expansion phase of the trial, at 28% tumor shrinkage in patients with previous therapy, the response rate NaPi2b patients achieving highly expressed 32% .

However, for the 10 Ming NaPi2b patients with high expression, the median duration of response only about 5 months. Finally, a patient related to the treatment died of pneumonia.

 

For XMT-1592 , as of August , researchers are exploring the correct dosage in a phase 1 trial. Mersana recently stated that it is possible to get NSCLC data in advance around the end of the year .

Once these data come out, the company will determine which of the two ADCs will enter the later NSCLC trial.

 

In addition to these two ADCs , Mersana expects that two ADC drugs will enter the clinic in 2022 . XMT-1660 is an ADC for B7-H4 .

There is also XMT-2056 , developed using Mersana ‘s Immunosynthen platform , and the specific target will be disclosed later.

 

 


0 8. AbbVie

  • Number of ADCs under development: 5
  • Estimated sales: /
  • Expected milestones: The first phase data of ABBV-647 and ABBV-011 are expected to be released in 2021.

When we talk about AbbVie’s ADC, it is hard to ignore the failure of rovalpituzumabtesirine (Rova-T).

 

Rova-T is designed to deliver PBD payload to small cell lung cancer expressing DLL3.

The drug is the core of AbbVie’s acquisition of Stemcentrx in 2016, and AbbVie prepaid US$5.8 billion in this transaction, including a US$4 billion milestone payment.

 

The early data for third-line therapy is promising, but a phase 3 trial for second-line therapy quickly moves in the opposite direction, because Rova-T shows a low response rate and is even better than traditional chemotherapy in terms of prolonging patient life.

 

Finally, the failure of the Phase 3 trial to test Rova-T as a maintenance therapy after first-line chemotherapy is the last straw.

AbbVie discontinued production of the drug and wrote off $5.1 billion related to the Stemcentrx transaction in 2018.

 

Despite the loss of approximately $10 billion, AbbVie still has five early ADCs in development.

 

Telisotuzumab vedotin is the leading ADC in the AbbVie pipeline. The drug targets c-Met and uses the tubulin inhibitor MMAE as the payload. Teliso-V as a monotherapy has provided positive phase 2 results.

Teliso-V induced a response in 53.8% of patients with non-squamous EGFR non-mutant c-Met high-expressing tumors.

 

In addition, the second pre-clinical c-Met ADC drug candidate, numbered ABBV-400, is expected to enter the clinic this year.

The drug uses a topoisomerase inhibitor payload. Compared with other c-Met drugs, the drug may have stronger anti-tumor efficacy.

 

In addition to the two c-Met ADCs, AbbVie recently reported preliminary phase 1 data of mirzotamab clezutoclax (ABBV-155) in solid tumors.

The drug is an anti-B7H3 antibody conjugated with a BCL-XL inhibitor as a payload.

 

AbbVie’s other two ADC projects are expected to receive early proof-of-concept data this year. They include ABBV-011 and cofetuzumab pelidotin (ABBV-647).

 

 


0 9.  Immunogen

  • Number of ADCs under development: 4
  • Estimated sales: None in 2021, USD 36 million in 2022
  • Expected milestones: Phase 3 data of mirvetuximab soravtansine in platinum-resistant ovarian cancer with high folate receptor-α expression is expected to be released in 2021. Data from the Phase 1/2 study of IMGN632 in plasmacytoid dendritic cell tumors is expected to be announced in the first half of 2022, and by the end of the year, the company plans to apply to initiate clinical trials of IMGN151.

ImmunoGen is the leader in the development of ADCs for ovarian cancer.

Its main drug candidate, mirvetuximab soravtansine (MIRV), conjugates the FRα targeting antibody to the DM4 payload.

 

Previously, the drug failed in the Phase 3 FORWARD I trial, which involved a wider range of people, including patients with moderate FRα expression levels. In this study, MIRV failed to surpass chemotherapy in terms of delaying tumor progression or time to death.

In patients with high FRα expression, MIRV did reduce this risk by about 30%, but due to the trial design, this improvement did not exceed the statistical significance standard.

 

Lessons learned from this trial, ImmunoGen designed the SORAYA trial so that only patients with high FRα expression screened by the PS2 + method can be included in the group.

The trial data is expected to be announced later in a few years. Another phase 3 trial called MIRASOL compares MIRV with chemotherapy in patients with high FRα expression and platinum resistance.

The trial data is expected to be reported in the third quarter of 2022.

 

In addition to platinum-resistant patients, ImmunoGen has also launched a new single-arm study called PICCOLO in patients with platinum-sensitive patients at a later stage.

 

If SORAYA, MIRASOL and PICCOLO can succeed, according to analyst estimates, MIRV’s sales in 2022 may reach 36 million US dollars.

 

In addition to MIRV, ImmunoGen also expects to submit an investigational new drug application for IMGN151 (an anti-FRα ADC).

There is also an anti-CD123 ADC in ImmunoGen’s pipeline for plasmacytoid dendritic cell tumors (BPDCN). The drug, coded as IMGN632, uses a coupling technology called SeriMab, which can produce a more uniform ADC.

 

 


10.  Sanofi

  • Number of ADCs under development: 1
  • Estimated sales: /
  • Expected milestone: Data from a Phase 3 trial of the new CEACAM5 targeting ADC in advanced NSCLC, and the company has begun basket trials in breast and pancreatic cancer.

Sanofi entered the ADC field through a cooperation with ImmunoGen in 2003, but the agreement has suffered setbacks.

In 2015, Sanofi abandoned the anti-blood cancer ADC being developed by the two companies. Then in 2017, it retuned the rest of the deal in order to obtain an exclusive license to develop the four ADCs they have been working with.

 

Sanofi subsequently abandoned two of the ADCs, and the status of the third ADC is currently unclear.

Only one remains: tusamitamabravtansine (formerly SAR408701), nicknamed “Tusa” by the company.

 

Tusa is aimed at a new target CEACAM5, which is a cancer kinesin, which is overexpressed in many tumor types but barely expressed in normal tissues.

It may provide a new way to attack cancer with minimal side effects.

 

Tusa is undergoing a phase 3 trial as a sole treatment for non-small cell lung cancer.

Sanofi also conducted two Phase 2 NSCLC trials, one combining Tusa with Merck’s Keytruda, and the other combining Cyramza, a VEGFR2 targeting antibody from Eli Lilly and Company.

The company recently began basket trials of the drug in other tumors overexpressing CEACAM5.

 

In a phase 2 study, 20% of NSCLC patients expressing high levels of CEACAM5 had a partial response to Tusa, and 42% of patients had stable disease.

Among patients who had previously taken anti-PD1/PD-L1 checkpoint inhibitors (such as Keytruda), the response rate was 18%.

 

 

 

Fiercepharma: 2021 Top Ten ADC Drug Competitors

(source:internet, reference only)


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