The next three months could bring a raft of important Food and Drug Administration decisions.
The agency is set to decide on new genetic medicines for sickle cell disease, including what would be the first CRISPR-based treatment cleared in the U.S. Expanded use of a multiple myeloma cell therapy is also on the table, as is a confirmatory approval for Amgen’s KRAS-targeting lung cancer drug Lumakras. And within the week, the regulator will issue a verdict that could help Alnylam Pharmaceuticals finally turn a consistent profit.
Here are five decisions to watch in the fourth quarter:
Alnylam’s Onpattro for cardiomyopathy of ATTR amyloidosis
At first glance, the decision whether to expand who can receive Alnylam’s drug Onpattro appears straightforward. Currently approved to treat nerve pain in people with a rare inherited condition called ATTR amyloidosis, Onpattro is in front of the FDA with data showing it also can help people with cardiovascular complications.
However, FDA officials gave the data a less-than-positive review, challenging the company’s assertions that gains observed in patient exercise duration and quality of life scores were meaningful. They also compared it to Pfizer’s approved drug tafamidis, which has data showing it reduced the risk of death and cardiovascular hospitalizations.
Expert advisers to the FDA, while acknowledging the limited data, voted 9-3 at a Sept. 13 meeting to recommend an approval. Some Wall Street analysts believe the FDA will follow that recommendation, although Stifel’s Paul Matteis judges it to be a 50-50 chance.
There are many more people with cardiomyopathy of ATTR amyloidosis than neuropathy and Alnylam is counting on an approval in that setting to help it become reliably profitable. The agency is expected to deliver its decision by Oct. 8. — Jonathan Gardner
Exa-cel and lovo-cel for sickle cell disease
People with sickle cell disease frequently experience debilitating bouts of pain when their red blood cells, bent into rigid crescents by their condition, block the flow of blood.
Two medicines now under review by the FDA promise to eliminate or sharply reduce these pain crises for many years, if not even longer. Their health impact could be profound, potentially changing the course of the disease.
Exa-cel, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, involves genetically editing a patient’s stem cells to produce high quantities of an alternate form of the needed hemoglobin protein that’s mutated in sickle cell.
By comparison, Bluebird bio’s lovo-cel adds an engineered form of a hemoglobin gene into a patient’s stem cells, giving those cells new instructions for making functional protein.
The FDA is set to decide on Vertex and CRISPR’s treatment by Dec. 8 and on Bluebird’s by Dec. 20. Before that, the agency will convene a panel of advisers on Oct. 31 to review exa-cel, which if approved would be the first CRISPR-based medicine cleared in the U.S.
Lovo-cel, which is similarly constructed to Bluebird’s Zynteglo treatment for beta thalassemia, won’t undergo the same advisory committee process. — Ned Pagliarulo
Bristol Myers Squibb and 2Seventy Bio’s Abecma for earlier multiple myeloma
Bristol Myers Squibb and biotechnology partner 2Seventy bio were first to market with a multiple myeloma cell therapy, winning an OK in March 2021 for their CAR-T treatment Abecma.
However, approval of the personalized therapy was limited to patients who had received at least four other prior medicines — a relatively narrow indication. Even so, Bristol Myers had trouble manufacturing enough Abecma to meet demand, forcing the company to ration the treatment’s availability.
Supply has since improved as Bristol Myers expanded production. But the company’s target market could soon grow larger, if the FDA grants an expanded clearance for Abecma in so-called triple-class exposed multiple myeloma. In that setting, study results showed the drug held patients’ cancer in check for significantly longer than did standard drug regimens.
The FDA is expected to make a decision by Dec. 16.
The agency’s verdict is important for Bristol Myers as the company faces competition from Johnson & Johnson and Legend Biotech, whose rival CAR-T therapy Carvykti decisively outperformed standard drugs in earlier-line multiple myeloma treatment. Those companies expect an FDA decision on their application for expanded use by late April. — Ned Pagliarulo
Amgen’s Lumakras for non-small cell lung cancer
On Oct. 5, the FDA will convene a panel of advisers to debate whether the agency should grant full approval to Lumakras, a first-of-its-kind cancer drug from Amgen that won an accelerated clearance two-and-a-half years ago.
The drug targets KRAS, a gene that’s often mutated in many lung, pancreatic and colon cancers. Its May 2021 approval, for a specific type of metastatic non-small cell lung tumor, came after decades of unsuccessful efforts to find ways to shut off mutant KRAS signaling.
As a condition of its clearance, the FDA required Amgen conduct follow-up testing to confirm whether Lumakras can stave off cancer growth or prolong patient survival, in addition to shrinking tumors.
While Lumakras succeeded in its confirmatory Phase 3 trial, the drug’s benefit was relatively modest. And results didn’t show a clear advantage in survival among those who received Lumakras, versus those who received chemotherapy.
FDA advisers will vote on whether that evidence merits converting Lumakras approval from conditional to full. While the agency doesn’t have to follow their advice, it usually does and will decide on Amgen’s application by December 24.
A positive vote could strengthen the odds of approval, which would boost Amgen as it studies Lumakras in earlier lines of treatment, other cancers and with other drugs. — Ned Pagliarulo
Pfizer’s etrasimod for ulcerative colitis
By 2030, Pfizer expects to add $25 billion in new revenue from products recently acquired in biotech acquisitions.
One of those products is an experimental drug called etrasimod that Pfizer picked up in a $6.7 billion deal for Arena Pharmaceuticals. Two late-stage clinical trials showed treatment could improve clinical remission rates in people with ulcerative colitis, a type of inflammatory bowel disease.
Pfizer expects to soon hear from the FDA on etrasimod’s approval in that condition, although it has only given a broad timeframe of the second half of this year.
A clearance would be the first step in a broader plan to prove the drug in other conditions like Crohn’s disease, alopecia areata and eczema. It could also help build a cushion against declining revenues from Pfizer’s COVID-19 vaccine and antiviral pill.
If approved, etrasimod would compete with Bristol Myers’ Zeposia, which arrived on the U.S. market two years ago and works similarly. — Ned Pagliarulo
Correction: A previous version of this story incorrectly referred to Bluebird bio’s sickle cell treatment lovo-cel.