ASCO 2022: Gilead’s tough weekend, bispecific progress and ‘gamma delta’ cell therapy – BioPharma Dive

For years, the American Society of Clinical Oncologys annual meeting has served as the main forum for advances in cancer immunotherapies like Merck & Co.s Keytruda and Bristol Myers Squibbs Opdivo.

While new data continue to emerge for those drugs and their competitors, this years conference was headlined by dramatic data for another type of cancer medicine from AstraZeneca and Daiichi Sankyo, which put pressure on rival Gilead. And with CAR-T therapies now established, attention has shifted to other emerging approaches for training the immune system to attack tumors.

Read on for updates on Gilead, bispecific antibodies for blood cancer and gamma delta cell therapy.

ASCO is an important conference for any biotech developing a cancer drug. But this years meeting was particularly so for Gilead, which has spent a decade and billions of dollars trying to build its oncology business. Analysts and investors were eagerly awaiting the details of a key study of the breast cancer drug Trodelvy, for which it paid $21 billion to acquire last year. Updates were also expected for magrolimab, another cancer medicine Gilead recently bought in a large deal.

The drugs either underwhelmed or were upstaged by others, however. Trodelvy led to a 1.5-month improvement over chemotherapy on a measure of tumor progression in a late-stage study of patients with a common form of metastatic breast cancer. The result fell short of the 2-month target doctors surveyed by analyst firm RBC Capital Markets felt would warrant meaningful use, according to a research note.

Trodelvy was also overshadowed by AstraZeneca and Daiichi Sankyos rival breast cancer drug, Enhertu, whose data in so-called HER2 low tumors were so striking they received a standing ovation at the meeting.

All the enthusiasm for Trodelvy has evaporated after those results, wrote Baird analyst Brian Skorney in a note on Sunday, adding that Enhertus likely approval in HER2 low breast cancer could limit Trodelvys revenue potential.

Analysts were similarly unimpressed by the latest data for magrolimab, a blood cancer drug that was slowed by safety concerns this year. Initial data showed a response rate of 50% for a combination of magrolimab and the chemotherapy azacitidine in an early-stage trial in myelodysplastic syndrome. That rate has fallen to 33% with additional data, barely surpassing whats been observed in tests of chemotherapy alone, Skorney wrote.

Complete response rates slipped in a Phase 1 acute myeloid leukemia study as well. The updates show Gileads drug has sufficient activity, though its perhaps not the home run it was initially hoped to be, wrote RBC analyst Brian Abrahams in a note to clients.

Gilead will likely need to show more before investors view the cancer portfolio as a major growth driver, Abrahams added. Shares ticked down 2% in early Monday trading.

The biotech did get a reprieve on Friday, however, announcing that regulators had lifted their last remaining hold on studies of magrolimab in lymphoma and multiple myeloma.

Cell therapy has become a powerful new treatment option for blood cancers like lymphoma and multiple myeloma. Approved drugs from Gilead, Bristol Myers Squibb, Novartis and Johnson & Johnson use souped-up immune cells genetically modified and infused back into patients to attack cancers.

But the approach, while potent, involves a painstaking manufacturing process that requires physicians to carefully time treatment. In multiple myeloma, Bristol Myers and J&J have struggled to keep up with demand, Stat News has reported, further complicating cell therapy's use.

While drugmakers expect to overcome those hurdles with time, they are busy advancing other ways to redirect immune cells to target cancer. One alternative uses an antibody to latch onto protein flags found on the surface of immune cells and their cancerous targets, bringing them into tumor-killing contact.

These so-called bispecific antibodies have already shown promise in some of the same blood cancers addressed by CAR-T cell therapies. At ASCO, Roche and J&J revealed updated clinical trial data supporting their respective medicines for lymphoma and multiple myeloma. AbbVie and partner Genmab, meanwhile, will present data on their lymphoma bispecific antibody at the European Hematology Association's meeting next weekend.

Scott Gottlieb, formerly Food and Drug Administration commissioner and currently a member of Pfizers board, pointed to bispecific antibody data as some of the most exciting to come out of ASCO this year.

"That data looks very promising," he said on CNBCs Squawkbox program Monday, noting the therapies from Roche and partners AbbVie and Genmab specifically.

Specifically, Roche's data showed treatment led to responses in half of patients with relapsed or refractory diffuse large B-cell lymphoma who were treated in the study. Nearly 40% went into remission.

Notably, about a third of the 154 participants had previously received CAR-T therapies, which have recently been approved in the U.S. for earlier use in treating advanced lymphoma.

"We still need longer follow-up for the bispecific antibodies," said Kerry Savage, a medical oncologist at The University of British Columbia, who discussed Roche's abstract at ASCO on Friday. "We don't know the curative potential yet, but it's certainly encouraging so far."

AbbVie and Genmab's results, which will be presented on Saturday at EHA, showed a slightly higher overall response rate of 63% and a similar remission rate of 39% among adults with several variations of relapsed or refractory large B-cell lymphoma.

J&J, meanwhile, brought updated data to ASCO for its multiple myeloma bispecific teclistamab, which were also published in The New England Journal of Medicine. The data showed treatment could beat back cancer and, in about 40% of patients, lead to remission.

"The high rate of deep and durable responses in this population indicates the potential for teclistamab to provide substantial clinical benefit to a broader population of patients," researchers wrote in NEJM.

The search for more convenient alternatives to personalized cell therapies has led to other off-the-shelf strategies besides bispecific antibodies. One emerging approach involves gamma delta T cells, rare white blood cells that can recognize a range of targets.

Adicet Bio, In8Bio, Immatics, among others, are developing treatments and multiple large companies have shown interest in their work. Bristol Myers Squibb just last week expanded an existing deal with Immatics, while Takeda and Johnson & Johnson have recently made investments, too.

Adicets program, a potential treatment for non-Hodgkins lymphoma, is the most advanced of the group, making its trial results an important proof point for the field.

Prior to the meeting, Adicet said four of six treated patients with a low or medium dose went into remission, with two of the three patients treated still cancer free after three months. Importantly, there were no serious immune or neurological side effects reported.

At ASCO, Adicet disclosed results from two additional patients as well as longer follow-up from others. While early, the findings are in the range with CAR-T therapy. As of May 31, six of eight patients including two at the highest tested dose had responded to treatment. All six initially went into remission.

Notably, these were heavily pretreated patients, three of whom whose disease had progressed after CAR-T. Adicet hasnt reported any cases of severe cytokine release syndrome, a common side effect of CAR-T.

Yet the treatments durability remains in question. Though four of the complete responses are ongoing, only one has lasted longer than six months. One patient previously in remission died from COVID-19, while another relapsed.

Adicet plans to pick a dose to advance into further testing. The company amended its trial to include a higher dose as well as potentially evaluate a multiple-dose regimen, a strategy other off-the-shelf cell therapy developers are testing as well.

Go here to see the original:
ASCO 2022: Gilead's tough weekend, bispecific progress and 'gamma delta' cell therapy - BioPharma Dive