InnoCare Captures the Attention of the Blood Cancer Community With Evidently Safer, More Effective Treatments

Blood cancer research has never been more dynamic, more productive, or more global. And that is a good thing for patients. 

There are countless new treatments in clinical trials for various types of lymphoma, leukemia, myeloma and other blood cancers. And they're coming from companies worldwide. 

Some of these new and promising modalities such as CAR T-cell immunotherapy, bispecific antibody treatment, gene therapies, natural killer (NK) treatments, targeted therapies, and more are already in the clinic, while many more are making their way through clinical trials.

 

Among the most successful new types of treatment for blood cancers are the Bruton's tyrosine kinase (BTK) inhibitors. 

 

These treatments inhibit the enzyme BTK, which is a crucial part of the B-cell receptor signaling pathway. Certain B-cell leukemias and lymphomas use B-cell receptor signaling for growth and survival.

BTK inhibitors can block this signaling and trigger the death of a cancer cell.

In the last several years, the clinical use of BTK inhibitors have changed the treatment landscape for chronic lymphocytic leukemia (CLL). 

 

BTK inhibitors in fact are the first targeted therapies to demonstrate a major improvement in progression-free survival for CLL patients compared with chemotherapy or chemo-immunotherapy.

 

Three different so-called BTK inhibitors -- Imbruvica from Pharmacyclics and Janssen, Calquence from AstraZeneca, and Brukinsa from BeiGene -- are already in the marketplace, and several more are being tested.

 

Among the new generation of BTK inhibitors, one of the most promising is orelabrutinib from InnoCare, a relatively new biopharmaceutical company that incorporated in China in 2015 and already has a presence in the United States.

 

InnoCare is developing what are potentially first-in-class and/or best-in-class drugs for the treatment of several types of cancer. 

 

The focus is on patients with blood cancers such as lymphoma, solid tumors, and autoimmune diseases with high unmet medical needs in the U.S., China and worldwide. 

 

InnoCare, which has branches in New Jersey, Boston, Beijing, Nanjing, Shanghai, Guangzhou and Hong Kong, brought more promising results to the recent American Society of Hematology (ASH) Annual Meeting.

 

An updated study result further confirms that orelabrutinib effectively treats relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

 

In a multicenter phase II trial, 80 patients with R/R CLL/SLL were enrolled. The overall response rate was 93.8 percent, with 26.3  percent seeing a complete response and 67.6 percent partial response. 

 

This is a significantly higher complete response rate in comparison with other BTK inhibitors at a similar median follow-up period.

 

The other significant news is that orelabrutinib was found to be well-tolerated. Most adverse events were mild to moderate. 

 

The evidence so far has shown that with each new generation of BTK inhibitor treatments, the efficacy and safety of the drug tends to improve. 

 

In an exclusive interview with The Reno Dispatch, Sean Zhang, InnoCare's Chief Medical Officer, said the updated data that was presented at ASH further confirms that orelabrutinib is effective in treating relapsed or refractory CLL patients with a relatively high rate of complete remission and durable response.

  

Orelabrutinib had received approval on Dec. 25, 2020 from the China National Medical Products Administration (NMPA) in two indications: the treatment of patients with r/r CLL/SLL, and the treatment of patients with r/r MCL. 

 

InnoCare is conducting a clinical study in US for both r/r MCL and r/r CLL/SLL indications. The FDA has granted Breakthrough Therapy Designation (BTD) to orelabrutinib for treatment of r/r MCL.

 

The InnoCare story is a remarkable one, for several reasons. The ascension of CEO Jasmine Cui, PD, is a positive story in and of itself.

 

A woman CEO at a major China biotech company had until recently been a rarity. But Cui has been described as one of the most innovative and brilliant cancer scientists and executives in the world. The company incorporated in 2015 and has a U.S. office in Princeton, NJ. 

Regarding the company’s lead product, orelabrutinib, Zhang said the drug is still in trials in the US, but it looks very promising.

 

"We have seen CLL patients with significantly higher complete response rates than other BTK inhibitors, durable response, and improved safety profiles,” he said.

 

"Orelabrutinib provides a favorable therapeutic choice for patients with R/R CLL/SLL and has great potential to be the best candidate for the combination therapy.” 

 

In addition to lymphoma, orelabrutinib shows great potential to treat such autoimmune disease as multiple sclerosis (MS). 

With the ability to cross the blood brain barrier, orelabrutinib has the potential to provide a clinically meaningful benefit on progression in all forms of MS. 

In July, 2021, InnoCare and Biogen, another international biotech company based in Cambridge, Mass., entered into a license and collaboration agreement for orelabrutinib for the potential treatment of MS.

This latest collaboration further illustrates InnoCare's international commitment to patients. 

Are Follicular Non-Hodgkin’s Lymphoma Patients Finally Getting Newer, Better Options to Treat Their Cancer?

It’s been nearly 23 years since I participated in a clinical trial after my follicular non-Hodgkin’s lymphoma recurred. When I was initially diagnosed with stage IV Follicular (FL) in early 1997, I went through five rounds of CHOP chemotherapy - cyclophosphamide, doxorubicin, vincristine and prednisone. It gave me two and 1/2 years of remission. But the treatment was rough.

When the cancer returned, instead of doing chemo again I chose to enroll in a clinical trial of a radio-immunotherapy (RIT) called Bexxar. I did my homework on the trial, and I then respectfully told my oncologist that this was my decision. He tried to talk me out of it. But I was resolute. 

 

Ultimately, my choice proved to be the right one. Multiple oncologists tell me that I am now cured of my follicular non-Hodgkin’s lymphoma. Despite the fact that many of my fellow patients were cured by Bexxar, the drug is no longer on the market for reasons that have absolutely nothing to do with its efficacy or safety.

 

Ever since Glaxo Smith Kline shelved Bexxar, as I wrote about here , and here, I've been on a mission to help my fellow follicular (FL) patients find newer, better options to treat their cancer.

 

I've worked with several dedicated, forward-thinking pharmaceutical companies to promote and encourage the study of new treatments for follicular NHL. It is desperately needed. 

But the research has been slow sledding. Follicular lymphoma, the second most common form of non-Hodgkin's lymphoma, remains an often relentless type of cancer that for many patients brings multiple relapses.

 

Since Rituxan was approved by the Food and Drug Administration (FDA) to treat follicular lymphoma in 1997, we've not seen too much movement in terms of challenging the standard of care for this horrible disease, or finding truly effective alternatives after patients recur. 

But at this month's American Society of Hematology (ASH) Annual Meeting, the largest gathering of blood cancer oncologists and scientists in the world, a boatload of promising trial data was presented from a variety of newer-generation medicines for follicular.

Viable new options are emerging at rapid pace. My hope and expectation is that some of these newer options will eventually replace the current standard of care and become first-line therapies. 

Below are just a few of the many treatments being studied that have great potential:

 

A Cell-Signal Blocker Emerges

One of the most interesting and potentially effective new drug technologies for follicular lymphoma is zandelisib. Previously called ME-401, zandelisib, from MEI Pharma in San Diego, is neither a chemotherapy nor a CAR T-cell immunotherapy nor a bispecific antibody.

Zandelisib is a cell-signal blocker. That simply means that it targets a protein in the body called P13K, which plays a key role in the growth and survival of the type of white blood cells that become abnormal in B-cell lymphomas. 

 

Blocking PI3K can help stop lymphoma cells from dividing or cause the cells to die.

MEI Pharma and Kyowa Kirin recently announced data from the Phase 2 TIDAL clinical trial of zandelisib in patients with relapsed or refractory follicular lymphoma.

In the trial, zandelisib showed a 70.3 percent objective response rate and 35.2 percent of patients achieved a complete response. And fewer than ten percent of the trial participants discontinued therapy due to side effects.

 

In an exclusive interview with The Reno Dispatch, Dan Gold, CEO at MEI Pharma and a gifted scientist who's been working in the lymphoma sector for many years, explained the status of this promising treatment. 

 

“We are very excited by the emerging zandelisib data, which indicate the potential to positively impact the standard-of-care for patients with relapsed or refractory follicular lymphoma," he said. 

 

"Once we have collected the final data from the follicular lymphoma patient cohort, we intend to discuss our plans to submit an accelerated approval marketing application with the FDA.” 

 

Gold added, "Our development efforts with our partner, Kyowa Kirin, to expand the utility of zandelisib include the ongoing Phase 3 COASTAL study evaluating zandelisib plus rituximab [Rituxan] in patients with relapsed or refractory follicular or marginal zone lymphomas.”

Bispecific Antibodies

 

But zandelisib is far from alone. There are multiple new treatments and modalities for FL that are showing very positive numbers in trials, including Roche’s Mosun.

 

In a clinical trial presented at ASH, Mosun, a bispecific antibody that redirects T cells to eliminate malignant B cells, induced "deep and durable remissions" in follicular NHL patients, including those with double-refractory disease.

 

"Notable updates coming out of ASH 2021 include experimental bispecifics such as mosunetuzumab [Mosun], which induced high response rates and durable responses for patients with relapsed/refractory follicular lymphoma,” Lee Greenberger, chief science officer at the Leukemia Society, told The Reno Dispatch.

“With a response rate of 70%, a complete response rate of 54%, and a median duration of response of 23 months, this could be a valuable addition to the treatment landscape in follicular lymphoma,"he said.

Greenberger added that Genentech's glofitamab, another bispecific for the treatment of relapsed or refractory follicular lymphoma, also showed significant response rates with good durability. 

"Bispecific antibodies offer the advantage of an off-the-shelf therapy with a performance that appears to be competitive compared to currently approved CAR T therapy for relapsed or refractory follicular lymphoma," he said. 

CAR T-Cell Immunotherapies

Not to be outdone, CAR T-cell immunotherapies, which have been the talk of the cancer research world for the last several years, are also making a strong statement about their place in the follicular space. 

 

Last March, the FDA granted Yescarta, a CAR T from Kite, a Gilead company, "accelerated approval" as a third-line therapy for adults with relapsed or refractory follicular. Yescarta, continued to shine at ASH this month, as did Kymriah, a Novartis CAR T product.

 

Both will likely challenge other drugs for third-line treatment, and eventually could become the new standard of care for FL and other types of lymphoma. 

The other good news about CAR T is that scientists continue to make progress in reducing cytokine release syndrome, the serious and sometimes even fatal side effect of this groundbreaking treatment.

 

Perhaps the most exciting piece of data in the Kymriah report presented at ASH is that no high-grade cytokine release syndrome was reported within eight weeks post-infusion and no new safety signals were identified.

"The ability to administer Kymriah, a potentially definitive treatment, in the outpatient setting may reduce the burden of therapy for patients and their care teams," Jeff Legos, global head of oncology & hematology development at Novartis, said in a press statement. 

"The breadth of follicular lymphoma data presented at this year's ASH demonstrate the potential for Kymriah to provide transformative results and a positive impact on health systems overall."