Topic: Biotech Generally, including Regulatory
Here's 2 cases of the dreaded CRL (complete response letter), where the FDA rejects a NDA or BLA. The FDA seems to be giving a lot of these and the OMER shorts are hoping Greg gets one.
November 17, 2020 07:32 AM ESTUpdated 07:59 AM R&DRegulatory
UPDATED: Alkermes is handed a CRL for ‘3831, marking another setback on the R&D front
Editor & Founder
Alkermes $ALKS is going to have to wait some more before launching its anti-psychotic combo drug ALKS-3831. The FDA has handed the biotech a CRL, rejecting the application in the company’s latest setback in R&D.
After getting a majority of the outside experts that reviewed the drug for the FDA to provide a thumbs up on approval, the biotech reported today that their manufacturing operations didn’t pass muster during their remote inspection of records — an alternative to a formal survey the agency adopted last summer as a result of the pandemic.
Alkermes emphasized that regulators didn’t raise any questions about the combo itself, which is designed to provide the anti-psychotic therapy Zyprexa without the threat of severe weight gain. There are no new requirements for additional studies. But the manufacturing review unveiled a problem with the tablet coating process at their factory in Wilmington, OH.
According to Alkermes:
The observations noted in the CRL were specific to certain development batches of ALKS 3831. The company believes this issue has since been resolved and that sufficient data is available to address these observations. Alkermes is preparing those data for submission and plans to work closely with the Agency to resolve these items in a timely manner and complete labeling discussions for the application.
Alkermes has run through a series of frustrations on the R&D front in recent years. A key depression drug failed a late-stage study in the spring of last year. And even if they get an OK on ‘3831 soon, the company still faces low expectations on the sales front, with peak estimates in some cases hovering around $300 million.
November 17, 2020 07:08 AM EST Regulatory
Penny stock player Adamis gets another CRL for high-dose naloxone as shares crater
The FDA has once again shut the door on micro cap biotech Adamis Pharmaceuticals’ high dose naloxone injection.
Regulators handed down the program’s second CRL in nearly 12 months, Adamis announced Monday, sending the penny stock spiraling. The new rejection came as a result of new chemistry, manufacturing and controls issues, though Adamis noted that none of the problems stemmed from the “extractables and leachables testing” problems that caused the first thumbs down.
“To me, it is very surprising to have new issues brought up this late in the review process,” CEO Dennis Carlo said in a statement. “We believe the comments and recommendations stated in the CRL can be addressed and overcome.”
Investors shunned shares at the news, sending Adamis $ADMP stock plunging roughly 41% in Monday trading.
The San Diego-based biotech works on specialty products, seeking to develop lower-cost alternatives to drugs already on the market. Adamis’ high-dose naloxone injection was aimed at treating opioid overdoses, as products like Narcan and Evzio generally use less than Adamis’ proposed 5 mg/0.5 mL dose.
Adamis re-submitted its application in May, about six months after first being turned away. Carlo said at the time that he felt the additional data addressed all the issues related to the FDA’s letter, and the company had entered into a distribution agreement for the program that would have, pending approval, totaled up to $26 million in upfront cash and milestone payments.
But regulators evidently saw something they didn’t like — again. Both CRLs for this candidate have now dealt with CMC concerns, and Adamis has requested a Type A meeting to resolve any outstanding questions.
This is not the first Adamis program to face rejection at the FDA. Back in February 2019, the agency handed back the company’s application for a lower-cost erectile dysfunction drug, saying Adamis did not provide enough data for a review. The experimental drug was a fast-disintegrating version of tadalafil, the same active ingredient in Eli Lilly’s Cialis.
Adamis’ main product is an epinephrine injectable called Symjepi, which is used to treat allergic reactions and anaphylactic shock similar to Mylan’s blockbuster Epipen. The plan was to use the same delivery system for their naloxone injection as Symjepi. The biotech is also developing cheaper alternatives in a range of acute respiratory diseases, such as Covid-19, influenza, asthma and COPD
(T)he issue here is not just related to a delay–it’s also a negative read on execution, with a potential follow-through onto stock sentiment, as this represents another regulatory setback for ALKS after the high profile rejection of ALKS5461 in MDD two years ago. These are obviously very different situations. But for ALKS, the pipeline is naturally a major driver of value creation and operating leverage, so this could increase pre-existing pressures to make a more concerted effort toward managing spend/investments.
Founder, Trust Intelligence
The foregoing is not investment advice.